SEARCH · Search PubMed

Results for “Cancer genomics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources

PubMed2002

Expression profile of EFNB1, EFNB2, two ligands of EPHB2 in human gastric cancer.

PURPOSE: We have previously reported that EPHB2 is overexpressed in gastric cancer; however, the expression profiles of its ligands, EFNB1 and EFNB2, are unknown. This study was designed to investigate the expression of EPHB2 and its ligands, EFNB1 and EFNB2, in human gastric cancer. METHODS: Semi-quantitative RT-PCR using (32)P was performed on human gastric cancer tissues and corresponding normal tissues (29 gastric cancer patients). RESULTS: EPHB2 was more highly expressed in tumor tissues than in normal tissues in 21 out of 29 (72.4%), in gastric cancer patients ( P = 0.01); EFNB1 and EFNB2 were highly expressed in 21 out of 29 (72.4%) ( P = 0.037) and 14 out of 29 (48.3%) patients, respectively. The overexpression of EPHB2 was frequently detected in both well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma [10/13 (76.9%) and 9/14 (64.3%), respectively]. On the other hand, the overexpression of EFNB1 was more frequently detected in poorly differentiated adenocarcinoma than in well-differentiated adenocarcinoma [12/14 (85.7%) and 7/13 (53.8%), respectively. P =0.027]. Elevated levels of EPHB2 and EFNB1 were detected in substantial subsets of early gastric cancers. Genomic alterations to these three genes in gastric cancer specimens were either not found or rarely found except for several rare variations of EPHB2. CONCLUSIONS: These findings suggest that not only the expression of EPHB2, but the expression of its ligand EFNB1 may have some relation with the oncogenesis of gastric cancer.

Base Sequence↗

PubMed2026

OLR1 drives gastric cancer progression through NF-κB activation and immunosuppressive macrophage polarization.

Gastric cancer remains a leading cause of cancer-related mortality worldwide, and the identification of clinically relevant biomarkers is critical for improving patient outcomes. Oxidized low-density lipoprotein receptor 1 (OLR1) has been implicated in tumor progression; however, its role in gastric cancer and the tumor microenvironment remains unclear. OLR1 expression and clinical significance were analyzed using The Cancer Genome Atlas (TCGA) dataset and validated in gastric cancer cell lines. Gain- and loss-of-function experiments, together with in vitro and in vivo assays, were performed to investigate the biological functions and underlying mechanisms of OLR1 in gastric cancer progression. OLR1 was significantly upregulated in gastric cancer and associated with unfavorable prognosis. Functional analyses demonstrated that OLR1 promoted gastric cancer cell proliferation, migration, and tumor growth. Mechanistically, OLR1 activated NF-κB signaling and facilitated macrophage polarization toward the M2 phenotype, thereby contributing to a protumorigenic microenvironment. OLR1 promotes gastric cancer progression through activation of NF-κB signaling and modulation of macrophage polarization. These findings identify OLR1 as a potential prognostic biomarker and therapeutic target for gastric cancer.

Humans↗

PubMed2004

Tamoxifen down-regulates CaMKII messenger RNA levels in normal human breast tissue.

Tamoxifen was proven to reduce the incidence of breast cancer by 49% in women at increased risk of the disease in the Breast Cancer Prevention Trial. In order to identify potential candidates to explain the preventive effect induced by tamoxifen on breast cancer, normal breast tissue obtained from 42 fibroadenoma patients, randomly assigned to receive placebo or tamoxifen, was analyzed by the reverse Northern blot and RT-PCR techniques. The cDNA fragments used on Northern blot membranes were generated by the Human Cancer Genome Project funded by the Ludwig Institute for Cancer Research and FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil). Total RNA was obtained from normal breast tissue from patients with clinical, cytological and ultrasound diagnosis of fibroadenoma. After a 50-day treatment with tamoxifen (10 or 20 mg/day) or placebo, normal breast tissue adjacent to the tumor was collected during lumpectomy with local anesthesia. One differentially expressed gene, Calcium/calmodulin-dependent protein kinase II (CaMKII), was found to be down-regulated during TAM treatment. CaMKII is an ubiquitous serine/threonine protein kinase that has been implicated in the diverse effects of hormones utilizing Ca2+ as a second messenger as well as in c-fos activation. These results indicate that the down-regulation of CaMKII induced by TAM might represent alternative or additional mechanisms of the action of this drug on cell cycle control and response to hormones in normal human breast tissue.

Antineoplastic Agents, Hormonal↗

PubMedDate not supplied

Genomic instability and breast cancer.

The loss of genomic stability is accepted as being one of the most important aspects of cancer. The correlation between genomic instability and cancer proneness in cases of known genetic syndromes (e.g. ataxia telengectasia, Fanconi anemia) is well established. This study was conducted to assess genomic instability in 19 patients with sporadic breast cancer. We used the comet assay on the lymphocytes of patients before radiotherapy and/or chemotherapy. The alkaline comet assay (single-cell gel electrophoresis) is a sensitive and rapid method for detecting DNA damage (single strand breaks and alkali-labile sites) in G(0) cells, at a single-cell level. This assay was achieved in vitro without irradiation and after exposure (dose ranging from 50 cGy to 5 Gy). The results show that the patients have higher baseline values than controls. At 2 Gy, the mean tail moment, score and the percentage of DNA in the tail increase for both groups but these values are much higher for patients. Our results show that the lymphocyte DNA of cancer patients is more damaged than that of controls with or without irradiation. Our hypothesis is that this baseline DNA damage reflect a genomic instability in sporadic breast cancer. This instability seems to increase after in vitro irradiation.

Aged↗

PubMed2000

A polymorphism of the interleukin-1 beta gene influences survival in pancreatic cancer.

Pro-inflammatory cytokines contribute to the cachexia associated with pancreatic cancer and stimulate the acute phase response which has been associated with shortened survival in such patients. Polymorphisms of cytokine genes may influence their production. The present study examined the effect of a polymorphism of the interleukin (IL)-1b gene upon the inflammatory state and survival in pancreatic cancer. Genomic DNA was obtained from 64 patients with pancreatic cancer and 101 healthy controls. Using the polymerase chain reaction and subsequent TaqI restriction enzyme digestion the subject's genotype for a diallelic polymorphism of the interleukin-1b gene was established. IL-1b production by peripheral blood mononuclear cells and serum C-reactive protein (CRP) levels from patients were also examined and survival noted. Patients homozygous for allele 2 of the IL-1b gene had significantly shorter survival than other groups (P = 0.0001). These patients also exhibited higher IL-1b production (P = 0.022). Possession of allele 2 was also associated with significantly shorter survival (median 144 vs 256 days, P = 0.034) and significantly higher CRP level (P = 0.0003). The possession of a genotype resulting in increased IL-1b production was associated with shortened survival and increased serum CRP level. This may reflect the role of IL-1b in inducing an acute phase protein response and cachexia in cancer or may be related to changes in tumour phenotype.

Adult↗

PubMed2025

TCGA molecular subtypes in endometriosis-associated ovarian cancer: a systematic review and meta-analysis.

BACKGROUND: Endometriosis-associated ovarian cancer (EAOC) mainly includes endometrioid ovarian cancer (ENOC) and clear cell ovarian cancer (CCOC). The Cancer Genome Atlas (TCGA) revealed four molecular subtypes of endometrial cancer (EC) in 2013, which have been proven pivotal in the diagnostic, prognostic and therapeutic domains of EC. Existing evidence indicates that EC and EAOC molecular analysis have similar significance. This review aims to investigate the distribution, staging and prognostic characteristics of molecular subtypes in EAOC. METHODS: PubMed, Embase and Web of Science were systematically searched from January 2013 to December 2023 using predefined keywords. Patient characteristics, including stage and prognostic characteristics, were extracted from the selected studies. Data analysis was carried out using Stata 14MP. RESULTS: A total of 6 studies involving 1,133 patients with ENOC and 4 studies comprising 377 patients with CCOC were included. ENOC had a higher frequency of the POLE mutation (POLEmut) subtype (odds ratio (OR) = 2.29, 95% CI: 1.03-5.11, p = 0.043) and the mismatch repair deficient (MMRd) subtype (OR = 3.54, 95% CI: 2.05-6.11, p = 0.000) than CCOC; ENOC had a lower frequency of the no specific molecular profile (NSMP) subtype (OR = 0.55, 95% CI: 0.41-0.73, p = 0.000) and the p53 abnormal (p53abn) subtype (OR = 0.97, 95% CI: 0.67-1.42, p = 0.893). The hazard ratios (HR) of the p53abn subtype in ENOC were disease-free survival (DFS) (HR = 3.25, 95% CI: 1.46-7.21, p = 0.004) and progression-free survival (PFS) (HR = 4.11, 95% CI: 2.86-5.92, p = 0.000). The DFS of the p53abn subtype in CCOC was calculated (HR = 5.52, 95% CI: 3.43-8.90, p = 0.000). CONCLUSION: The TCGA subtypes of EC may exhibit similarities in prognosis between ENOC and CCOC.

Humans↗

PubMed2026

The European Health Data Space and the Secondary Use of Sensitive Health Data.

INTRODUCTION: The European Health Data Space (EHDS) is one of the European Union's most ambitious data-governance projects. It aims to create a common framework through which electronic health data can be accessed and reused across Member States for care, research, innovation, policy, and public-interest purposes. Its practical viability depends not only on digital infrastructure, but also on legal, ethical, and organisational harmonisation, particularly for genetic and genomic data. METHODS: This paper examines the EHDS with emphasis on the secondary use of health data. It reviews the EHDS institutional architecture, discusses Finland's Findata as a national model for structured access, and analyses challenges for data holders and data donors, including interoperability, governance burdens, privacy protection, residual re-identification risk, and genomic-data sensitivity. RESULTS: A cross-border cancer-genomics case study shows that the EHDS can streamline data discovery and the routing of access requests, but does not by itself eliminate legal fragmentation, heterogeneous ethics review, and consent-related barriers. DISCUSSION: Effective implementation will require harmonisation beyond infrastructure, including clearer consent standards, more consistent ethics procedures, interoperable metadata, and proportionate safeguards for genomic data.

Electronic Health Records↗

PubMed2026

Integrated multi-omics analysis and functional experiments reveals PPAP2C as a potential prognostic biomarker and therapeutic target in breast cancer.

BACKGROUND: This study aims to systematically elucidate the clinical significance and biological function of the phospholipid phosphatase (PLPP) family member (PPAP2C) phosphatidic acid phosphatase type 2C in breast cancer, and to evaluate its potential as a prognostic biomarker and therapeutic target. METHODS: Gene expression data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases were integrated to characterize the expression profile of PLPP family members, focusing on PPAP2C in breast cancer. The prognostic value of PPAP2C, initially identified at the mRNA level (TCGA, (METABRIC) Molecular Taxonomy of Breast Cancer International Consortium, Gene Expression Omnibus (GEO)), was confirmed at the protein level by immunohistochemistry (IHC) on tissue microarrays (TMA). The oncogenic functions of PPAP2C were investigated in triple-negative breast cancer (TNBC) cells through CRISPR-Cas9-mediated knockout and ectopic overexpression, with assessment of key phenotypes including proliferation, colony formation, migration, and invasion. In vivo validation was subsequently performed using an MDA-MB-231 xenograft model. RESULTS: PPAP2C exhibits the most significant overexpression pattern across 33 cancer types (upregulated in 16 cancers, downregulated in only 3). Compared with normal tissues, PPAP2C showed specific overexpression in breast cancer tissues and was significantly associated with advanced clinical stages and aggressive subtypes (HER2+ and TNBC). Survival analysis demonstrated that high PPAP2C expression correlated with significantly shorter overall survival and disease-free survival, which was further validated in METABRIC and GEO cohorts. Tissue microarray analysis confirmed higher PPAP2C protein positivity in tumor tissues (94.7%) than in adjacent normal tissues (59.7%), with worse OS and RFS in high-expression groups. Multivariate analysis identified PPAP2C as an independent prognostic factor for OS. Functional experiments revealed that PPAP2C knockout (via 5-bp/1-bp frameshift mutations) suppressed TNBC cell proliferation, colony formation, migration, and invasion, while overexpression enhanced these phenotypes. In vivo studies further demonstrated complete tumor regression in MDA-MB-231 xenografts upon PPAP2C knockout. CONCLUSION: This study identifies PPAP2C as a key oncogenic driver and a robust independent prognostic biomarker in breast cancer. The findings provide compelling evidence that PPAP2C represents a promising therapeutic target, offering a new strategic avenue for precision therapy, particularly for aggressive breast cancer subtypes.

PLPP2↗

PubMed2004

Chromosome segregation and genomic stability.

The acquisition of genomic instability is a crucial step in the development of human cancer. Genomic instability has multiple causes of which chromosomal instability (CIN) and microsatellite instability (MIN) have received the most attention. Whereas the connection between a MIN phenotype and cancer is now proven, the argument that CIN causes cancer remains circumstantial. Nonetheless, the ubiquity of aneuploidy in human cancers, particularly solid tumors, suggests a fundamental link between errors in chromosome segregation and tumorigenesis. Current research in the field is focused on elucidating the molecular basis of CIN, including the possible roles of defects in the spindle checkpoint and other regulators of mitosis.

Animals↗

PubMed2000

Chromosomal alterations in ulcerative colitis-related and sporadic colorectal cancers by comparative genomic hybridization.

Both ulcerative colitis (UC)-related and sporadic colorectal cancers are thought to evolve through a multistep process of genomic instability, accumulation of genomic alterations, and clonal expansion. This process may involve different genomic changes in UC-related cancers than in sporadic cancers because of the origin of UC-related cancers in an inflammatory field. This study was designed to define the specific genomic events occurring in UC-related cancers. Comparative genomic hybridization (CGH) was performed on 32 UC-related and 42 stage-matched sporadic colorectal cancers. The mean number of chromosomal alterations per case was similar in the UC-related and sporadic tumor groups (8.6 in UC, 8.1 in sporadic). The 2 tumor groups shared many chromosomal alterations: losses on 18q (78% UC v69% sporadic), 8p (53% v50%), 17p (44% v57%), and gains on 8q (63% v45%), 20q (44% UC v67%), and 13q (44% UC v38%). However, differences in the frequency and timing of specific alterations were observed. Chromosome 5q was lost in 56% of UC-related but in only 26% of sporadic cancers. Alterations of chromosome 8 were associated with stage progression in UC-related, but not in sporadic cancers. In contrast, 18q loss was associated with stage progression in sporadic cancers only. Thus, differences in the frequency and timing of individual chromosomal alterations suggest that genetic progression in these 2 tumor groups may follow multiple pathways.

Adult↗

PubMed2026

Overexpression of a subset of long intergenic noncoding RNAs in uterine serous carcinoma predicts poor prognosis.

The evaluation and prediction of uterine serous carcinoma (USC), a type of endometrial cancer that is more severe than endometrioid adenocarcinoma, remain challenging. Long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers. This study assessed the expression patterns and prognostic values of long intergenic noncoding RNAs (lincRNAs) in USC. RNA sequencing, copy number variation (CNV), and clinical data from The Cancer Genome Atlas were used to investigate various lncRNAs in endometrial cancer. LincRNAs, a major subclass of lncRNAs, exhibit specific expression patterns modulated by CNVs and act as predictors of poor prognosis, survival, and recurrence in USC. Functional analyses were conducted to investigate the roles of lncRNAs in USC. Finally, the expression of these lincRNAs was verified in 32 pairs of USCs collected from the hospital over 3 years. A series of lincRNAs were found to be specifically expressed in USC compared with other lncRNAs and regulated by CNV. Moreover, these specific upregulated lincRNAs, particularly ENSG00000281406, ENSG00000226791, ENSG00000269903, and ENSG00000204277, demonstrated poor prognoses for survival and recurrence in USC. Functionally, our analysis showed that ENSG00000281406 positively correlated with the Wnt signaling pathway, whereas ENSG00000226791, ENSG00000269903, and ENSG00000204277 negatively correlated with the T-cell receptor signaling pathway. Importantly, we confirmed that ENSG00000204277 negatively correlated with CD8+ T-cell immune infiltration in USC. Our results highlight that these lincRNAs can serve as new biomarkers for the prognostic prediction of USC. In particular, ENSG00000204277 may be used as a therapeutic target for USC.

Humans↗

PubMed2025

TMSB10 drives prostate cancer aggressiveness via immune microenvironment regulation.

Thymosin β10 (TMSB10) has emerged as a key player in the progression of prostate cancer, significantly influencing the tumor immune microenvironment. Pan-cancer analysis from The Cancer Genome Atlas (TCGA) revealed that TMSB10 is upregulated across multiple cancer types, particularly in prostate cancer, where high TMSB10 expression correlates with poorer patient outcomes. Functional assays using prostate cancer cell lines LNCaP and DU145 showed that TMSB10 silencing suppresses cell proliferation, migration, and invasion, while overexpression enhances these oncogenic processes. Furthermore, co-culture experiments demonstrated that TMSB10 overexpression skews macrophage polarization, decreasing the population of M1-type macrophages while increasing M2-type macrophages. This shift reduces immune cell cytotoxicity and alters cytokine secretion, highlighting TMSB10's role in immune evasion. These findings establish TMSB10 as a pivotal factor in prostate cancer biology, promoting tumor aggressiveness and modulating the immune response within the tumor microenvironment. TMSB10 presents a promising therapeutic target for prostate cancer, offering new avenues for treatments aimed at altering the tumor immune landscape. This research also provides a foundation for further exploration of TMSB10's role in other cancers.

Male↗

PubMed2003

Allelotype of 28 human breast cancer cell lines and xenografts.

Heterozygous loss of relatively large chromosomal regions is a hallmark of the inactivation of tumour suppressor genes. Searching for deletions in cancer genomes therefore provides an attractive option to identify new tumour suppressor genes. Here, we have performed a genome-wide survey for regions exhibiting allelic loss in 24 commercially available breast cancer cell lines and four breast cancer xenografts, using microsatellite analysis. The assembled allelotype revealed an average fractional allelic loss of 0.34. A total of 19 arms had low allelic loss frequencies (<25%) and 17 arms had moderate allelic loss frequencies (25-50%). Five chromosomal arms were deleted in more than half of the breast cancer samples (8p, 10q, 13q, 17p, and 17q). Three of these frequently lost chromosomal arms had not been identified as such by comparative genome hybridisation, illustrating the higher sensitivity of microsatellite analysis for the detection of allelic losses. As we present allelic loss data of individual samples, our allelotype should not only aid the identification of new breast cancer genes but also provides a baseline for myriad studies involving these breast cancer cell lines.

Alleles↗

PubMed2001

Intrachromosomal genomic instability in human sporadic colorectal cancer measured by genome-wide allelotyping and inter-(simple sequence repeat) PCR.

We have used genome-wide allelotyping with 348 polymorphic autosomal markers spaced, on average, 10 cM apart to quantitate the extent of intrachromosomal instability in 59 human sporadic colorectal carcinomas. We have compared instability measured by this method with that measured by inter-(simple sequence repeat) PCR and microsatellite instability assays. Instability quantitated by fractional allelic loss rates was found to be independent of that detected by microsatellite instability analyses but was weakly associated with that measured by inter-(simple sequence repeat) PCR. A set of seven loci were identified that were most strongly associated with elevated rates of fractional allelic loss and/or inter-(simple sequence repeat) PCR instability; these seven loci were on chromosomes 3, 8, 11, 13, 14, 18, and 20. A lesser association was seen with two loci flanking p53 on chromosome 17. Coordinate loss patterns for these loci suggest that at least two separate sets of cooperating loci exist for intrachromosomal genomic instability in human colorectal cancer.

Alleles↗

PubMed2005

Going on a cancer gene hunt.

NIH is preparing to announce plans for the pilot phase of their proposed Human Cancer Genome Project. This initiative seeks to provide a complete list of the mutations that give rise to cancer.

Genes, Neoplasm↗

PubMed2026

MRI-based radiomics model for predicting VEGFA expression and prognosis in lower-grade glioma.

BACKGROUND: Gliomas are the most common primary tumors of the central nervous system. Their treatment remains highly challenging, with high rates of associated disability and mortality. Conventional prognostic indicators no longer adequately satisfy the clinical demands of precision medicine. Therefore, it is essential to further explore novel prognostic biomarkers to enable accurate risk stratification and to provide new reference indicators for personalized precision therapy. PURPOSES: This study aimed to investigate the prognostic significance of vascular endothelial growth factor A (VEGFA) in patients diag nosed with lower-grade gliomas (LGGs) using an MRI based radiomics model. METHODS: Data regarding VEGFA expression and clinical records of LGG patients were retrieved from The Cancer Genome Atlas (TCGA). Corresponding preoperative MRI data were obtained from The Cancer Imaging Archive (TCIA) for radiomic feature extraction. Patients were stratified into high- and low- VEGFA expression groups based on survival information from the current cohort using the survminer package. The overall survival (OS) was assessed using Kaplan-Meier analysis and Cox proportional hazards regression. Predictive models were developed using logistic regression (LR), and model performance was evaluated via receiver operating characteristic (ROC) curve analysis, with area under the curve (AUC) values reported. An optimized model incorporating the Akaike information criterion (AIC) was also constructed (AIC-LR). RESULTS: VEGFA expression was significantly associated with OS (P = 0.002). Multivariate Cox regression confirmed VEGFA as an independent prognostic factor (hazard ratio [HR] = 2.545, 95% confidence interval: 1.422-4.555). Furthermore, VEGFA expression correlated with immune infiltration levels, particularly of M1 and M2 macrophages and T follicular helper cells, and was associated with enrichment in Wnt signaling and B cell receptor signaling pathways. The LR and AIC-LR models demonstrated acceptable predictive performance, with AUCs of 0.728 (95% CI: 0.612-0.843) and 0.725(95% CI: 0.612-0.839) in the training cohort, and 0.704 (95% CI: 0.562-0.847) and 0.718(95% CI: 0.576-0.861) in the validation cohort, respectively. CONCLUSIONS: The MRI based radiomics model showed potential for noninvasive assessment of VEGFA expression and may provide auxiliary information for prognostic evaluation in LGG. Further validation in larger samples and independent external cohorts is required before clinical application.

Radiomics↗

PubMed2025

The protective role of γδ T cells in endometrial cancer.

Γδ T cells are non-conventional T cells that are not MHC restricted and have T cell receptors (TCRs) that are stimulated by phosphoantigens, stress-induced proteins, lipids, and other antigens. These cells are prognostic across cancer types in The Cancer Genome Atlas (TCGA) but have not been well studied in endometrial cancer, which has a rising incidence and mortality rate. Endometrial cancer patients have variable responses to checkpoint inhibitors which are related to the molecular subtype of their cancer. As such, there is a pressing need to understand the immune microenvironment in endometrial cancer. This study addresses this gap in knowledge by investigating γδ T cell repertoires and transcriptomes in this disease site. γδ T cell repertoires were obtained for 543 endometrial cancer patients within the TCGA and from 5 endometrial cancer patients in the single cell dataset SRP349751 using TRUST4. GLIPH2 was used to identify TCRs predicted to bind the same antigen. Transcriptomes were investigated in the single cell dataset. DNA Polymerase Epsilon Exonuclease (POLE) and Microsatellite Instability High (MSI-H) endometrial cancer subtypes had the most γδ T cell infiltration. Vδ1 and Vδ3 γδ T cell infiltration was prognostic independent of stage and molecular subtype. GLIPH2 analysis revealed TCRδ motifs for TDK, YTD, and GEL were public across all four molecular subtypes and were present in the single cell data set. Vδ1 γδ T cell transcriptomes were associated with cytotoxicity and recent TCR stimulation. These data support further investigation of immunotherapies targeting γδ T cells in endometrial cancer.

Humans↗

PubMed2026

SYT8 Drives Colorectal Cancer Progression and Immune Evasion via the SETD1A-H3K4me3 Axis.

By integrating transcriptomic data from The Cancer Genome Atlas, Gene Expression Omnibus, and a self-established colorectal cancer (CRC) cohort, it was identified that synaptotagmin 8 (SYT8) is significantly up-regulated in tumors and is predictive of poor prognosis. Single-cell RNA sequencing, immunohistochemistry, and immunofluorescence experiments demonstrate that SYT8 expression is largely confined to tumor cells, predominantly in the nucleus. Functional assays reveal that depletion of SYT8 impairs, whereas its overexpression enhances, CRC cell proliferation and invasion. Transcriptomic profiling indicates an enrichment of cell cycle and epithelial-mesenchymal transition signatures. Mechanistically, co-immunoprecipitation/mass spectrometry identifies SET domain containing 1A (SETD1A) as a direct SYT8-interacting partner. The SYT8-SETD1A axis forms a positive-feedback loop that increases histone H3 lysine 4 trimethylation (H3K4me3) levels and drives the transcription of protumorigenic genes. Immune profiling further indicates that high SYT8 expression correlates with increased regulatory T-cell infiltration, suggesting an immunosuppressive microenvironment and potential resistance to immunotherapy. Collectively, SYT8 promotes CRC progression through the SETD1A/H3K4me3-mediated activation of the cell cycle, induction of epithelial-mesenchymal transition, and remodeling of the immune microenvironment. Therefore, SYT8 is established as a prognostic biomarker and serves as a therapeutic target in colorectal cancer.

Humans↗