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PubMed2026

HLA class I expression and tumor immune infiltration together shape colon cancer immune contexture.

BACKGROUND: The relative contribution of HLA class I molecules-including classical HLA class Ia (HLA-A, -B, -C) and non-classical HLA class Ib (HLA-E, -F, -G)-to shaping the tumor immune microenvironment in colon cancer remains insufficiently defined. We investigated how their expression patterns relate to immune infiltration and clinical outcome. METHODS: In a retrospective cohort of 280 colon cancers, we assessed HLA class Ia and class Ib expression and quantified CD45-positive immune cell infiltration by immunohistochemistry. These features were correlated with clinicopathological variables, microsatellite instability (MSI) status, and previously established genomic immune signatures. RESULTS: High HLA class Ia expression and increased CD45-positive cell infiltration were each associated with improved overall, disease-specific, and progression-free survival. CD45-positive density correlated strongly with Immunologic Constant of Rejection scores. HLA class Ia loss was more frequent in advanced stages and in MSI-H tumors. Among HLA class Ib molecules, only HLA-E expression was associated with favorable disease-specific and progression-free survival. Integrative analysis identified three immune phenotypes with distinct prognostic profiles; tumors characterized by high HLA class Ia expression, low HLA class Ib expression, and high CD45-positive infiltration had the best outcomes. CONCLUSION: Colon cancer immunogenicity is shaped by coordinated patterns of HLA class I expression and immune infiltration. Integrating HLA class Ia/Ib expression with immune cell density provides a refined stratification of tumor immune phenotypes and may support personalized immunotherapeutic decision-making.

Antigen presentation↗
PubMed2024

Inhibiting the expression of spindle appendix cooled coil protein 1 can suppress tumor cell growth and metastasis and is associated with cancer immune cells in esophageal squamous cell carcinoma.

Inhibiting the expression of spindle appendix cooled coil protein 1 (SPDL1) can slow down disease progression and is related to poor prognosis in patients with esophageal cancer. However, the specific roles and molecular mechanisms of SPDL1 in esophageal squamous cell carcinoma (ESCC) have not been explored yet. The current study aimed to investigate the expression levels of SPDL1 in ESCC via transcriptome analysis using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. Moreover, the biological roles, molecular mechanisms, and protein networks involved in SPDL1 were identified using machine learning and bioinformatics. The cell counting kit-8 assay, EdU staining, and transwell assay were used to investigate the effects of inhibiting SPDL1 expression on ESCC cell proliferation, migration, and invasion. Finally, the correlation between the SPDL1 expression and cancer immune infiltrating cells was evaluated by analyzing data from the TCGA database. Results showed that SPDL1 was overexpressed in the ESCC tissues. The SPDL1 expression was related to age in patients with ESCC. The SPDL1 co-expressed genes included those involved in cell division, cell cycle, DNA repair and replication, cell aging, and other processes. The high-risk scores of SPDL1-related long non-coding RNAs were significantly correlated with overall survival and cancer progression in patients with ESCC (P < 0.05). Inhibiting the SPDL1 expression was effective in suppressing the proliferation, migration, and invasion of ESCC TE-1 cells (P < 0.05). The overexpression of SPDL1 was positively correlated with the levels of Th2 and T-helper cells, and was negatively correlated with the levels of plasmacytoid dendritic cells and mast cells. In conclusion, SPDL1 was overexpressed in ESCC and was associated with immune cells. Further, inhibiting the SPDL1 expression could effectively slow down cancer cell growth and migration. SPDL1 is a promising biomarker for treating patients with ESCC.

Humans↗
PubMed2025

Construction of a prognostic model for gastric cancer based on immune infiltration and microenvironment, and exploration of MEF2C gene function.

BACKGROUND: Advanced gastric cancer (GC) exhibits a high recurrence rate and a dismal prognosis. Myocyte enhancer factor 2c (MEF2C) was found to contribute to the development of various types of cancer. Therefore, our aim is to develop a prognostic model that predicts the prognosis of GC patients and initially explore the role of MEF2C in immunotherapy for GC. METHODS: Transcriptome sequence data of GC was obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and PRJEB25780 cohort for subsequent immune infiltration analysis, immune microenvironment analysis, consensus clustering analysis and feature selection for definition and classification of gene M and N. Principal component analysis (PCA) modeling was performed based on gene M and N for the calculation of immune checkpoint inhibitor (ICI) Score. Then, a Nomogram was constructed and evaluated for predicting the prognosis of GC patients, based on univariate and multivariate Cox regression. Functional enrichment analysis was performed to initially investigate the potential biological mechanisms. Through Genomics of Drug Sensitivity in Cancer (GDSC) dataset, the estimated IC50 values of several chemotherapeutic drugs were calculated. Tumor-related transcription factors (TFs) were retrieved from the Cistrome Cancer database and utilized our model to screen these TFs, and weighted correlation network analysis (WGCNA) was performed to identify transcription factors strongly associated with immunotherapy in GC. Finally, 10 patients with advanced GC were enrolled from Sun Yat-sen University Cancer Center, including paired tumor tissues, paracancerous tissues and peritoneal metastases, for preparing sequencing library, in order to perform external validation. RESULTS: Lower ICI Score was correlated with improved prognosis in both the training and validation cohorts. First, lower mutant-allele tumor heterogeneity (MATH) was associated with lower ICI Score, and those GC patients with lower MATH and lower ICI Score had the best prognosis. Second, regardless of the T or N staging, the low ICI Score group had significantly higher overall survival (OS) compared to the high ICI Score group. For its mechanisms, consistently, for Camptothecin, Doxorubicin, Mitomycin, Docetaxel, Cisplatin, Vinblastine, Sorafenib and Paclitaxel, all of the IC50 values were significantly lower in the low ICI Score group compared to the high ICI Score group. As a result, based on univariate and multivariate Cox regression, ICI Score was considered to be an independent prognostic factor for GC. And our Nomogram showed good agreement between predicted and actual probabilities. Based on CIBERSORT deconvolution analysis, there was difference of immune cell composition found between high and low ICI Score groups, probably affecting the efficacy of immunotherapy. Then, MEF2C, a tumor-related transcription factor, was screened out by WGCNA analysis. Higher MEF2C expression is significantly correlated with a worse OS. Moreover, its higher expression is also negatively correlated with tumor mutation burden (TMB) and microsatellite instability (MSI), but positively correlated with several immunosuppressive molecules, indicating MEF2C may exert its influence on tumor development by upregulating immunosuppressive molecules. Finally, based on transcriptome sequencing data on 10 paired tumor tissues from Sun Yat-sen University Cancer Center, MEF2C expression was significantly lower in paracancerous tissues compared to tumor tissues and peritoneal metastases, and it was also lower in tumor tissues compared to peritoneal metastases, indicating a potential positive association between MEF2C expression and tumor invasiveness. CONCLUSIONS: Our prognostic model can effectively predict outcomes and facilitate stratification GC patients, offering valuable insights for clinical decision-making. The identified transcription factor MEF2C can serve as a biomarker for assessing the efficacy of immunotherapy for GC.

Humans↗
PubMed2025

Lactate dehydrogenase a is a crucial biomarker that affects the prognosis, chemotherapy effect, and immune infiltration of breast cancer.

PURPOSE: Lactate dehydrogenase A (LDHA) is a key node in tumor growth, metabolism, and invasion and is upregulated across multiple cancers. However, the molecular mechanisms by which LDHA influences breast cancer (BC) remain unclear. We analyzed public datasets and an institutional cohort to clarify the relationship between LDHA and BC, with the aim of informing future therapeutic strategies. PATIENTS AND METHODS: Using The Cancer Genome Atlas (TCGA), we assessed LDHA expression in BC and examined its associations with tumor mutational burden (TMB), immune cell infiltration, immune checkpoint molecules, and drug sensitivity. We integrated multiple databases and used Kaplan-Meier analyses to evaluate prognostic value. To explore biological functions of LDHA, we performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). We then analyzed BC patients receiving neoadjuvant chemotherapy (NAC) at Harbin Medical University Cancer Hospital to test the relationship between serum lactate dehydrogenase (LDH) and pathological complete response (pCR). Finally, we used National Health and Nutrition Examination Survey (NHANES) data to examine the association between serum LDH and mortality. RESULTS: LDHA was upregulated in BC tissues, and higher expression was significantly associated with worse overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). Functional analyses indicated enrichment of metabolic pathways, such as glycolysis. LDHA expression correlated with multiple immune cell populations, suggesting involvement in the tumor immune microenvironment. Lower LDHA expression was associated with greater sensitivity to several chemotherapeutic agents. In our institutional cohort, patients with lower serum LDH were more likely to achieve pCR, and LDH was an independent predictor of pCR. In NHANES, elevated serum LDH was linked to increased mortality risk. CONCLUSION: Our findings suggest that LDHA expression and serum LDH levels are promising prognostic biomarkers for survival and may predict chemotherapy response in BC patients. These results highlight the clinical relevance of LDHA-mediated metabolic pathways. However, as a correlational study, our findings warrant further validation through functional experiments to confirm LDHA's role as a potential therapeutic target.

Humans↗
PubMed2026

Integrated Pan-Cancer, Single-Cell, and Spatial Transcriptomic Analyses Identify ZDHHC12 as a Biomarker Associated with Macrophage Infiltration and the Immune Landscape in Glioma.

BACKGROUND: The tumor immune microenvironment (TME) critically influences cancer progression and therapeutic response. However, the pan-cancer expression landscape, prognostic relevance, and spatial distribution of ZDHHC12 remain incompletely characterized. This study investigated the prognostic value of ZDHHC12 and its associations with immune microenvironmental features and drug sensitivity. METHODS: Data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets were used to evaluate ZDHHC12 expression and prognosis across cancer types. Immune infiltration analyses, single-cell RNA sequencing, and spatial transcriptomics were integrated to characterize the associations of ZDHHC12 with the cancer immunity cycle and the spatial architecture of glioma. Drug sensitivity and immunotherapy-related metrics were assessed using pharmacogenomic databases and computational prediction models. RESULTS: ZDHHC12 was aberrantly expressed across multiple tumors and was associated with patient prognosis. Its expression was broadly correlated with immune cell recruitment- and activation-related signatures. In glioma, single-cell and spatial transcriptomic analyses showed enrichment of ZDHHC12 in monocyte/macrophage populations and spatial co-localization with BAK1, CD68, and CD163. ZDHHC12 expression was also associated with predicted drug sensitivity and immunotherapy-related metrics. CONCLUSION: ZDHHC12 may serve as a candidate pan-cancer prognostic biomarker. In glioma, its expression is associated with macrophage-enriched and immunosuppressive microenvironmental features. Functional studies are required to establish causality and determine its therapeutic relevance.

GBM↗
PubMed2026

Comprehensive analysis suggests CRIF1 is a potential target in breast cancer associated with prognosis and immune infiltration.

BACKGROUND: CRIF1 is a multifunctional factor that regulates cell biological processes such as the cell cycle, cell proliferation, and energy metabolism, and it is a new molecule that contributes to the poor prognosis of many malignancies. However, its involvement in breast cancer development is not fully known. MATERIALS AND METHODS: To investigate the relationship between CRIF1 expression, prognosis, and clinical characteristics using The Cancer Genome Atlas (TCGA-BRCA). The relationship between CRIF1 expression and the immunological microenvironment was investigated using CIBERSORT, ESTIMATE. Breast tissue and CRIF1 expression were validated by IHC. A tiny interfering plasmid was designed to transiently transfect breast cancer cell lines, and proliferation-related functional tests were carried out. The effect of sh CRIF1 on tumor formation was confirmed using a subcutaneous tumor experiment in naked mice. RESULTS: We discovered that CRIF1 was highly elevated in breast cancer tissues and associated with a poor prognosis. CRIF1 stimulates breast cancer cell proliferation, migration, and invasion. Knockdown decreased PI3K/AKT/mTOR signaling, which boosted autophagy activity. Immune infiltration research revealed that patients with high CRIF1 expression had higher CD8+ T cell expression but reduced macrophage M2 expression. CONCLUSION: Upregulation of CRIF1 in breast cancer cells enhances malignant behavior, which may be mediated by PI3K/AKT/mTOR signaling and is linked to cellular autophagy.

Humans↗
PubMed2025

Integrated multi-omics analysis reveals TMEM147 as an immunosuppressive prognostic biomarker in LUAD.

TMEM147, an endoplasmic reticulum (ER) membrane protein, is implicated in lung adenocarcinoma (LUAD) progression, although its precise role remains unclear. To elucidate its function, this study integrated bioinformatics analyses with experimental validation. First, TMEM147 expression was assessed using TCGA and GEO datasets, with validation performed in LUAD cell lines. Survival analysis evaluated its prognostic significance. Subsequently, Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and single-sample gene set enrichment analysis (ssGSEA) were employed to identify associated functional pathways and interactions within the tumor immune microenvironment. Transcription factor binding predictions and in vitro functional assays (migration, invasion, proliferation) further characterized TMEM147's role. Results indicated that TMEM147 was significantly upregulated in LUAD and correlated with poor outcomes in patients. FLI1 was predicted as a key transcriptional regulator of TMEM147. Furthermore, TMEM147 expression influenced immune cell infiltration profiles and was associated with pathways involved in ribonucleoprotein biogenesis and oxidative phosphorylation (OXPHOS). Importantly, silencing TMEM147 significantly reduced cancer cell migration, invasion, and proliferation. These findings collectively suggest that TMEM147 promotes LUAD progression and holds potential as both a prognostic biomarker and a therapeutic target.

Bioinformatics analysis↗
PubMed2026

Elevated Triggering Receptor Expressed on Myeloid Cells 2 Expression in Tumor-Associated Macrophages Suppresses Cytotoxic T Cell Infiltration and Facilitates Immune Escape in Colorectal Cancer.

BACKGROUND & AIMS: Emerging evidence supports a crucial role for tumor-associated macrophages in shaping the immunosuppressive tumor microenvironment. Furthermore, research has identified that the triggering receptor expressed on myeloid cells 2 has immunomodulatory functions. The present investigated the potential effect of triggering receptor expressed on myeloid cells 2 expression in tumor-associated macrophages on facilitating immune evasion in colorectal cancer. METHODS: Immunohistochemical analysis of clinical specimens, complemented by extensive data mining from The Cancer Genome Atlas, revealed a significant upregulation of triggering receptor expressed on myeloid cells 2 in colorectal cancer-associated tumor-associated macrophages, with this upregulation exhibiting a correlation with poor patient prognosis. RESULTS: Mechanistically, triggering receptor expressed on myeloid cells 2+ tumor-associated macrophages were found to drive fibroblast activation through transforming growth factor-&#x3b2; signaling, inducing fibroblast-activated protein-positive cancer-associated fibroblasts that secrete collagen I/III to establish dense peritumoral barriers. Spatial profiling revealed that these fibrous structures physically impede CD8+ T-cell infiltration, restricting cytotoxic lymphocytes to stromal compartments. Intriguingly, triggering receptor expressed on myeloid cells 2 deficiency enhanced the secretion of matrix metalloproteinase 13 by macrophages, thereby promoting extracellular matrix degradation and improving T-cell penetration. In vivo, Trem2-knockout mice showed a reduction in tumor growth with enhanced intratumoral CD8+ T-cell infiltration compared with wild-type controls. CONCLUSIONS: Our findings establish triggering receptor expressed on myeloid cells 2+ tumor-associated macrophages as central regulators of stromal remodeling and suggest that therapeutic targeting of the triggering receptor expressed on myeloid cells 2/transforming growth factor-&#x3b2;/fibroblast-activated protein pathway may overcome immune resistance in patients with colorectal cancer.

Colorectal Neoplasms↗
PubMed2026

Analysis and validation of abnormal signaling pathways and immune cell infiltration characteristics in digestive system cancers based on peroxisome-related genes.

BACKGROUND: Although emerging evidence suggests a role for peroxisomes in tumorigenesis, their functions in digestive cancers remain unclear. This study aims to investigate the association between peroxisomes and digestive tract tumors. METHODS: To systematically investigate peroxisomal functions in digestive cancers, we first constructed and validated tumor-specific prognostic signatures based on peroxisome-related genes (PRGs) through univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. We then characterized the tumor immune microenvironment (TIME) with CIBERSORT, X-CELL, and EPIC algorithms, and identified tumor-specific and common signalings via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Focusing on hepatocellular carcinoma (HCC), we experimentally validated peroxisome-related therapeutic responses by profiling signature genes in radioresistant cells and an orthotopic transarterial chemoembolization (TACE) rat model. PEX13 knockdown further assessed peroxisomal role in radiosensitivity and targeted therapy response. Clinical relevance of PEX13 was evaluated in HCC cohort. Single-cell RNA sequencing dataset and lipidomics further revealed peroxisomal mechanisms in HCC progression. Finally, peroxisomal function in colorectal cancer (CRC) was validated in vitro. RESULTS: Novel peroxisome-related prognostic signatures demonstrated strong predictive power in HCC, colon adenocarcinoma, rectal adenocarcinoma, pancreatic adenocarcinoma, gastric adenocarcinoma, esophageal adenocarcinoma, esophageal squamous cell carcinoma, and cholangiocarcinoma. High-risk patients displayed an immunosuppressive microenvironment, characterized by increased infiltration of regulatory T cells, M2 macrophages, Th2 cells, or cancer-associated fibroblasts, or Th1 cells' reduction. Peroxisomes engaged in several distinct yet convergent pathways, most notably "positive regulation of response to stimuli". HCC prognostic genes were dynamically regulated in response to therapeutic stimuli, including radiotherapy, targeted therapy, and TACE. Clinically, the expression of PEX13 was markedly upregulated in tumor tissues from therapy-resistant HCC patients. Mechanistically, peroxisomal dysfunction induced by silencing PEX13 in HCC or UBE2D2 in CRC may overcome therapeutic resistance (radiotherapy/ lenvatinib resistance in HCC, radioresistance in CRC) through reprogramming lipid metabolism. CONCLUSIONS: Peroxisomes act as pivotal regulators of digestive cancer progression by modulating signaling pathways, the TIME, therapeutic resistance, and lipid metabolism. Targeting peroxisomal function, particularly in high-risk subgroups of HCC and CRC, warrants further exploration as a promising therapeutic strategy.

Peroxisomes↗
PubMed2026

MS4A3 as a potential prognostic biomarker for colon cancer: integrated analysis of expression patterns and immune cell infiltration.

BACKGROUND: Membrane Spanning 4-Domains A3 (MS4A3) has been confirmed to possess significant tumor-suppressive potential in various malignancies. However, its expression characteristics and clinical prognostic value in colon cancer (CC) still lack systematic and in-depth investigation. This study aimed to systematically investigate the expression pattern, prognostic value, immune microenvironment association, and biological function of MS4A3 in CC through integrated bioinformatics analyses and experimental validation. METHODS: This study utilized The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) cohort to screen for genes significantly associated with CC and combined multiple independent Gene Expression Omnibus (GEO) datasets to validate the expression patterns and prognostic significance of MS4A3. Key biological pathways were identified through gene set enrichment analysis (GSEA), and tumor immune infiltration characteristics were evaluated using the CIBERSORT algorithm. Additionally, the expression of MS4A3 and its impacts on cellular functions were validated at the cellular level through quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, Cell Counting Kit-8 (CCK-8), EdU, Transwell, and TUNEL assays. RESULTS: Analysis of public datasets revealed that MS4A3 is significantly downregulated in CC tissues, and its low expression is an independent risk factor for shortened overall survival (OS). GSEA indicated that MS4A3 downregulation is closely associated with the aberrant activation of the pentose phosphate pathway. Immune infiltration analysis showed that low MS4A3 expression is closely linked to the enrichment of M2 macrophages and neutrophils, as well as the upregulation of multiple immune checkpoint genes. In vitro experiments further confirmed that MS4A3 was lowly expressed in CC cell lines. Its overexpression significantly inhibited CC cell viability, proliferation, migration, and invasion, while simultaneously promoting cell apoptosis. CONCLUSIONS: MS4A3 expression is significantly decreased in CC tissues and is significantly correlated with poor prognosis, suggesting that this gene may serve as a potential prognostic biomarker.

MS4A3↗
PubMed2026

Mature Tertiary Lymphoid Structures in Breast Cancers Are Associated With Antitumor Immunity and Better Prognosis.

Tertiary lymphoid structures (TLSs) are immune cells accumulated in nonlymphoid tissues, with an inner core of B cells encompassed by T cells. The aim of this study was to evaluate the clinical importance of mature TLSs in breast cancer, including their association with immunotherapy response and their role in modulating the tumor immune microenvironment. We analyzed histopathological data of 726 consecutive primary breast cancers and transcriptomic data of 824 breast cancer samples from the publicly available The Cancer Genome Atlas database to estimate the clinical and immunological values of mature TLSs in breast cancer. Additionally, we utilized pretreatment transcriptomic data of 69 patients with breast cancer from the publicly available I-SPY2 clinical trial to investigate the relation between TLS-related gene signatures and patient responses to immune checkpoint inhibitors. The existence of mature TLSs was identified in &#x2053;5.6% (41/726) of all patients with breast cancer (hormone receptor-positive human epidermal growth factor receptor-2 negative (HR+HER2-): 0.92%; triple-negative breast cancer (TNBC): 14.96%; and human epidermal growth factor receptor-2 positive (HER2+): 10.98%) and was independently associated with improved recurrence-free survival after adjusting for subtypes, tumor-infiltrating lymphocyte levels, and tumor stage after the multivariable Cox regression analysis in our patient cohort. Notably, the presence of mature TLSs was related to immune cell infiltration in our breast cancer patient cohort. In line with these findings, TLS-related gene signatures analyzed through transcriptomic data reliably reflected the existence of mature TLSs and were related to better clinical responses to immune checkpoint inhibitors in patients with breast cancer. In conclusion, our findings show that mature TLS formation is linked with immune cell infiltration, contributes to a favorable prognosis, and may function as a potential complementary biomarker for immunotherapy response in breast cancer.

Humans↗
PubMed2026

Pan-cancer analysis identifies KANSL2 as a cell-cycle-associated regulator of tumor progression and immunity in liver hepatocellular carcinoma.

KANSL2, a core component of the NSL histone acetyltransferase complex, has been implicated in tumorigenesis. However, its pan-cancer relevance and functional role in liver hepatocellular carcinoma (LIHC) remain unclear. Multi-omics data from TCGA, GEO, and HPA were integrated to systematically evaluate KANSL2 expression, clinical significance, genomic alterations, and immune associations across cancers. Functional enrichment, immune infiltration analyses, and single-cell transcriptomics were performed. In vitro assays were conducted to validate the biological effects of KANSL2 in LIHC cells. KANSL2 is broadly upregulated across cancers and exhibits strong diagnostic performance. Elevated KANSL2 expression correlates with unfavorable prognosis, particularly in LIHC. Mechanistically, KANSL2 and its co-expressed genes are enriched in cell-cycle progression. KANSL2 expression is also closely associated with immune infiltration and immunoregulatory signaling within the tumor microenvironment, with single-cell data indicating preferential expression in proliferative T-cell subsets. Functional experiments demonstrate that KANSL2 silencing suppresses proliferation, migration, and invasion, and induces G2/M phase arrest in LIHC cells. Notably, its effects on apoptosis are limited, suggesting that KANSL2 primarily drives tumor progression through cell-cycle-dependent mechanisms. This study identifies KANSL2 as a key regulator of tumor progression and immune remodeling in LIHC. By promoting malignancy predominantly via cell-cycle control, KANSL2 represents a promising biomarker for diagnosis and prognosis, and a potential therapeutic target.

Carcinoma, Hepatocellular↗
PubMed2026

BAP1 Loss in Pleural Mesothelioma Is Associated With Reduced Soluble CCL2 in Patient Effusion, Abrogated CCL2-Mediated Monocyte Recruitment In Vitro.

OBJECTIVES: Pleural mesothelioma is an incurable cancer of the cell layer lining the chest wall and lung. Patients frequently present with pleural effusion, which is often drained for symptom relief and enables minimally invasive sampling of the tumour environment, including immune cells and related soluble factors. Most of the mesothelioma tumours exhibit loss of BRCA1-associated protein 1 (BAP1), a multifunctional tumour suppressor protein. Here, we aim to elucidate the effect of BAP1 loss on the mesothelioma microenvironment through profiling soluble factors within pleural effusion. METHODS: A custom panel of 22 soluble factors was measured by Luminex assay and enzyme-linked immunosorbent assay in an initial cohort of 40 patients with known BAP1 status. Validation was performed by enzyme-linked immunosorbent assay in an independent cohort of 100 cases. Secretion of soluble factors and chemoattraction of monocytes were characterised using a CRISPR-mediated BAP1 deletion model in a mesothelioma and a lung cancer cell line. Immune cell infiltration, estimated by CIBERSORT, was further explored in the Cancer Genome Atlas -MESO cohort. RESULTS: Soluble C-C motif chemokine ligand 2 (CCL2) was approximately 55% to 60% lower in pleural effusion from BAP1-loss cases in both independent cohorts. Deletion of BAP1 reduced CCL2 secretion in vitro and abolished CCL2-mediated chemoattraction of monocytes in both mesothelioma and lung cancer cell lines. In the Cancer Genome Atlas -MESO cohort, BAP1-mutant tumours exhibited a reduction in estimated macrophage content. CONCLUSION: Loss of BAP1 impairs CCL2 secretion into pleural effusions, potentially influencing monocyte recruitment into the tumour microenvironment.

BAP1↗
PubMed2023

MYH16 upregulation is associated with lung adenocarcinoma aggressiveness and immune infiltration.

Myosin heavy chain 16 (MYH16) may significantly affect cell cycle progression. Nevertheless, there is a lack of evidence about the clinical relevance of MYH16 upregulation in pan cancers, including lung adenocarcinoma (LUAD). MYH16 expression patterns were evaluated in various bioinformatics databases using The Cancer Genome Atlas data set. Clinical and pathological factor data were employed to risk-stratify patients. The Kaplan-Meier plotter approach was used to estimate survival rates. Tumor immune infiltration was explored via the TIMER tool, and gene set enrichment analysis (GSEA) was used to identify the pathways involved in MYH16 upregulation. The results showed that MYH16 was abnormally upregulated in pan cancers, including LUAD. MYH16 expression induction in LUAD was found to be related to the tumor stage. Furthermore, MYH16 upregulation was correlated with LUAD development and worse overall survival, particularly in women. Notably, MYH16 overexpression in LUAD tissues corresponded to the amount of immune infiltration in the tumor. Additionally, univariate Cox hazard regression analysis revealed that MYH16 may be an independent prognostic indicator for LUAD. Furthermore, a nomogram was constructed according to MYH16 expression and clinical characteristics. BMP6 expression deficiency may be a key factor contributing to MYH16 upregulation in LUAD. Finally, GSEA demonstrated that MYH16 might mediate meiosis and gene silencing through RNA signaling pathways. This study, for the first time, showed that MYH16 upregulation in LUAD is associated with various risk factors, increased cancer aggressiveness, enhanced infiltration of tumor immune cells, and reduced survival rates.

Female↗
PubMed2024

SPOP expression is associated with tumor-infiltrating lymphocytes in pancreatic cancer.

BACKGROUND: Speckle Type POZ Protein (SPOP), despite its tumor type-dependent role in tumorigenesis, primarily as a tumor suppressor gene is associated with a variety of different cancers. However, its function in pancreatic cancer remains uncertain. METHODS: SPOP expression and the association between its expression and patient prognosis and immune function were evaluated using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), The Tumor Immune Estimation Resource 2.0 (TIMER2.0) database, cBioportal, and various bioinformatic databases. Enrichment analysis of SPOP and the association between SPOP expression with clinical stage and grade were analyzed using the R software package. Then immunohistochemistry (IHC) was used to estimate the correlation between SPOP and tumor-infiltrating lymphocytes (TILs) in patients with pancreatic cancer. RESULTS: As part of our study, we assessed that SPOP was anomalously expressed in kinds of cancers, associated with clinical stage and outcomes. Meanwhile, SPOP also played a crucial role in the tumor microenvironment (TME). The expression level of SPOP was significantly correlated to tumor-infiltrating immune cells (TICs) in pancreatic cancer. CONCLUSIONS: Our study uncovered the potential corrections in SPOP with TICs, suggesting that SPOP may act as a biomarker for immunotherapy in pancreatic cancer.

Humans↗
PubMed2026

Pan-cancer landscape of APEX1 expression and genomic alterations: Associations with clinical outcomes and functional validation in lung cancer.

This pan-cancer study systematically evaluated APEX1 expression, genomic alteration status, and prognostic value across 13,270 tumors and 2544 normal tissues from TCGA and GTEx. APEX1 overexpression was prominent in bladder, breast, and colon adenocarcinomas and correlated with advanced tumor stages and survival outcomes in a cancer-type-specific manner, with unfavorable associations in selected tumor contexts and an opposite favorable association in KIRC. Low-frequency APEX1 genomic alterations require cautious interpretation and may be associated with adverse outcomes in selected tumor contexts. Statistical methods including t-tests, ANOVA, Cox regression, Benjamini-Hochberg false-discovery rate correction for cohort-wise OS analyses, and log-rank tests were used to correlate APEX1 expression or alteration status with survival outcomes. The findings suggest that APEX1 expression and low-frequency genomic alterations are associated with tumor progression and worse patient outcomes in selected cancer contexts. This study supports APEX1 as a candidate prognostic indicator requiring further validation and suggests its potential value for future clinical stratification research. The pan-cancer approach improves contextual breadth, and the large sample size adds robustness. The observed relevance of APEX1 across malignancies supports further evaluation of its value for risk stratification and treatment planning. Future prospective studies are needed to validate its clinical utility. This work contributes to the growing field of DNA repair-related biomarkers and may inform future studies of APEX1-targeted therapeutic strategies.

Apurinic/Apyrimidinic Endonuclease 1↗
PubMed2026

RECQL correlates with immune infiltration and serves as a prognostic biomarker and therapeutic predictor in gastric cancer.

BACKGROUND: RecQ-like helicase (RECQL), a member of the RecQ-like DNA helicase family, plays a crucial role in maintaining genomic stability. However, its relevance in gastric cancer (GC) has not been fully investigated. This study aimed to explore the clinical significance, biological functions, and potential role of RECQL in the tumor immune microenvironment of GC through comprehensive bioinformatics analyses and in vitro experiments. METHODS: Weighted gene co-expression network analysis (WGCNA), differential expression analysis, and least absolute shrinkage and selection operator (LASSO) regression were performed using public datasets [The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD), GSE150290] to identify key genes associated with GC progression. Subsequently, key pathways were identified through functional enrichment analysis, while immune infiltration and spatial transcriptomic analyses were conducted to characterize RECQL expression and its association with the tumor immune microenvironment. Finally, the effects of RECQL knockdown on the biological function of GC cells were assessed through Cell Counting Kit-8 (CCK-8), colony formation, scratch, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. RESULTS: RECQL was significantly upregulated in GC tissues and correlated with advanced clinical stage and poor prognosis. Gene set enrichment analysis (GSEA) revealed a strong association between high RECQL expression and DNA repair pathway. Immune infiltration analysis indicated significant enrichment of M2 macrophages in the high-RECQL group, along with upregulation of immune checkpoint molecules including PDCD1, CTLA4, and CD274. Spatial transcriptomics further demonstrated co-localization of RECQL with myeloid cell-enriched regions in tumor parenchymal areas. Furthermore, in vitro experimental results indicated that RECQL was highly expressed in GC cell lines, and its knockdown effectively inhibited the viability, proliferation, and migration capabilities of HGC-27 cells, while enhancing their apoptosis. CONCLUSIONS: RECQL serves as a promising biomarker and potential therapeutic target in GC.

DNA repair↗
PubMed2026

A pan-cancer analysis of MEX3D in human tumors.

BACKGROUND: MEX3D, a member of the MEX3 RNA-binding protein family, has emerged as a potential regulatory molecule in cancer. However, its role across different tumor types remains largely unexplored. METHODS: We conducted a pan-cancer analysis of MEX3D using transcriptomic and proteomic data from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Expression patterns, clinical correlations, survival outcomes, genetic alterations, RNA modification associations, immune infiltration, and functional enrichment were systematically evaluated. RESULTS: MEX3D was significantly dysregulated in numerous cancers at both mRNA and protein levels. Its expression correlated with tumor stage in ACC, LIHC, OV, SKCM, and THCA. Elevated MEX3D expression was associated with poor overall survival (OS) and disease-specific survival (DSS) in multiple malignancies, including ACC, LGG, LUAD, and MESO. Genetic alteration analysis revealed frequent amplifications and mutations, particularly in SARC and OV. MEX3D was positively correlated with RNA modification-related genes (m1A, m5C, m6A) and immune regulatory genes such as CD276, TGFB1, VEGFA, and ICOSLG. Additionally, MEX3D expression showed significant associations with tumor mutational burden (TMB), microsatellite instability (MSI), and cancer-associated fibroblast infiltration. Functional enrichment analyses indicated that MEX3D-related genes are involved in reproductive cellular processes, RNA binding, the Hippo signaling pathway, and microRNA-related oncogenic pathways. CONCLUSION: This pan-cancer analysis highlights the heterogeneous expression and cancer-specific prognostic significance of MEX3D. MEX3D is associated with immune infiltration, immune regulatory genes, RNA modification-related genes, TMB/MSI, and pathways involved in gene regulation and tumor progression. These findings suggest that MEX3D may participate in cancer-specific post-transcriptional and microenvironmental regulatory networks.

Biomarker↗