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PubMed2026

Estrogen Receptor, GATA-3, TTF-1, and KRAS in Endometrial Carcinoma of No Specific Molecular Profile: Prognostic or Diagnostic Markers?

Endometrial carcinoma with no specific molecular profile (NSMP) is a clinicopathologically heterogeneous group of diseases with an overall intermediate prognosis. Prognostic refinement is needed for better personalized treatment. The updated European Society of Gynecological Oncology-European Society for Radiotherapy and Oncology-European Society of Pathology guidelines for endometrial carcinoma stratify NSMP according to histotype and estrogen receptor (ER) status. ER (with other ancillary markers) also helps differentiate histotypes of endometrial carcinoma. This study describes clinicopathological characteristics of ER-positive and -negative-NSMP endometrial carcinoma. Furthermore, we investigate the prognostic and diagnostic significance of ER, GATA3, TTF1, and KRAS in a large and relatively unselected NSMP carcinoma cohort. POLE sequencing results and immunohistochemistry for p53, mismatch repair proteins, and ER were available for 930 samples of endometrial carcinoma. Within NSMP cases (n = 377), 22 samples presented ER staining in <1% of the carcinoma cells, 5 cases in 1% to 9%, and 350 cases in ≥10%. ER expression ≥10% predicted an excellent outcome (comparable with POLE-mutated cases) in univariable analysis, where ER negativity (<10%) was associated with a poor outcome (comparable with p53 abnormal cases). Most ER-positive NSMP cases were low-grade endometrioid carcinomas, whereas most ER-negative NSMP cases were nonendometrioid or high-grade endometrioid carcinomas. In addition to high-risk histotype, ER negativity was associated with various other clinicopathological risk factors. In multivariable analysis adjusting for histotype and other risk factors, ER did not independently predict disease progression (P = .814). No disease-related deaths were observed in the rare (n = 3) patients with ER-negative-low-grade endometrioid carcinoma. GATA3/TTF1 positivity and KRAS mutation were discovered not only in mesonephric-like carcinoma but also in endometrioid carcinoma. No prognostic relevance was found for these markers. In conclusion, the different prognosis of ER-positive vs ER-negative-NSMP endometrial carcinoma is not attributable to ER status itself but rather to its strong correlation with histotype and other clinicopathological risk factors. Limited specificity of GATA3, TTF1, and KRAS warrants caution in their use as diagnostic markers of mesonephric-like carcinoma.

Humans↗

PubMed2026

Potential evaluation of SULT1A3 as an early diagnostic marker for nasopharyngeal carcinoma: a study based on serum proteomics screening and ELISA validation.

BACKGROUND: Nasopharyngeal carcinoma (NPC) represents a highly prevalent and aggressive malignancy endemic to Southeast Asia. Early and accurate diagnosis is critical to improving survival outcomes; however, the absence of robust, stage-specific biomarkers remains a key obstacle to clinical implementation of early screening strategies. METHODS: We performed untargeted serum proteomic profiling using mass spectrometry in 15 treatment-naïve early-stage NPC patients and 15 VCA-IgA-positive healthy controls. Bioinformatics analyses were conducted to identify differentially expressed proteins (DEPs). Machine learning (random forest combined with recursive feature elimination) was employed to prioritize candidate biomarkers, which were subsequently verified using enzyme-linked immunosorbent assay (ELISA) in independent sample cohorts. RESULTS: In total, 1,428 serum proteins were identified, among which 1,410 were reliably quantified. We observed 31 upregulated and 189 downregulated proteins in NPC patients relative to controls. Spearman correlation analysis revealed significant associations: LTA4H (leukotriene A4 hydrolase) levels correlated with serum cell infiltration (r = 0.383, p = 0.032) and CD8 + T-cell abundance (r = 0.408, p = 0.021); both SULT1A3 (sulfotransferase family 1 A member 3) and FGL1 (fibrinogen-like protein 1) levels were positively associated with M1 macrophage infiltration (r = 0.510, p = 0.003 and r = 0.430, p = 0.015, respectively). In a preliminary validation cohort (n = 80), ELISA yielded AUC values of 0.631 (95% CI: 0.515-0.736, p = 0.04) for LTA4H, 0.787 (95% CI: 0.681-0.871, p < 0.001) for SULT1A3, and 0.688 (95% CI: 0.575-0.787, p = 0.002) for FGL1. In large-scale independent validation, SULT1A3 achieved an AUC of 0.826 (95% CI: 0.766-0.876; sensitivity = 78.89%, specificity = 75.47%) in cohort 1 (n = 196) and 0.796 (95% CI: 0.723-0.857; sensitivity = 76.67%, specificity = 76.67%) in cohort 2 (n = 150). CONCLUSIONS: Through an integrated workflow combining proteomic screening, machine learning prioritization, and multi-stage ELISA validation, we identified SULT1A3 as a candidate serum-based biomarker for early detection of NPC. Preliminary findings suggest that SULT1A3 may have potential utility in clinical screening, though further validation in independent, multi‑center cohorts is required.

Humans↗

PubMed1979

Cystic fibrosis protein, a confirmed diagnostic marker for detecting heterozygote carriers: significance in relation to future screening and to a proposed primary defect in alpha 2-macroglobulin.

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Blood Proteins↗

PubMedDate not supplied

Plasminogen activator as a diagnostic marker for preneoplastic cells in human gynecologic specimens.

A modified fibrin-agar overlay assay was used to measure the fibrinolytic activity in human cervical epithelial cells. The fibrinolytic activity results from a cell-associated serine protease that acts as a plasminogen activator. An enzymatic and morphologic comparison of individual normal and abnormal cells reveals that about 50% of the dysplastic and carcinoma in situ cells contain high levels of the activator. Forty percent of morphologically normal metaplastic cells also exhibit high activities of plasminogen. Forty percent of morphologically normal metaplastic cells also exhibit high activities of plasminogen activator. Most normal intermediate and superficial epithelial cells and all erythrocytes and leukocytes are inactive. The frequency of plasminogen activator-containing cells was somewhat higher in cytomorphologically abnormal samples than in normal samples.

Carcinoma in Situ↗

PubMed1979

Angiogenesis capacity as a diagnostic marker for human eye tumors.

Solid tumors have the capacity to continuously stimulate the proliferation of new capillaries. Aliquots (0.1 cc) of aqueous humor were aspirated from the anterior chamber of the eye of 38 patients undergoing elective ophthalmologic surgery. The material was lyophilized and then inplanted on the chorioallantoic membrane (CAM) of 10-day-old chick embryos for bioassay. The angiogenesis capacity of each sample was graded as negative or positive. Nine of 10 patients with histologically proven retinoblastoma had positive vascular responses. Seven of 11 patients with choroidal malignant melanoma had a positive response to their aqueous humor on the CAM. Aqueous samples from eyes with an iris and ciliary body malignant melanoma and a metastatic breast carcinoma to the iris had a positive angiogenic response. By contrast, only one of 15 patients undergoing operation for cataracts, glaucoma, or other nonmalignant ocular disease showed an angiogenesis response. The one patient who a positive assay later developed lymphocytic leukemia. These studies show that certain intraocular tumors display angiogenesis capacity before clinically evident neovascular changes of floating tumor cells are seen. Patients without tumors showed no angiogenesis response.

Angiogenesis Inducing Agents↗

PubMed2026

Exploring the Genetic Link between Irritable Bowel Syndrome and Polycystic Ovary Syndrome: Bidirectional Mendelian Randomization and Machine Learning Approaches.

BACKGROUND: Research has shown a certain correlation between polycystic ovary syndrome (PCOS) and irritable bowel syndrome (IBS). The study aims to determine the directionality and underlying biological processes influencing the relationship between these two disorders. METHODS: We explored the causal relationship between IBS and PCOS by conducting a comprehensive bidirectional Mendelian randomization (MR) analysis using five different methods and conducted robustness assessments. We extracted differentially expressed genes from the IBS and PCOS datasets for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Additionally, we developed a protein-protein interaction (PPI) network and applied the Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine (SVM) methodologies to pinpoint key diagnostic markers. Diagnostic efficacy was further assessed through Receiver Operating Characteristic (ROC) curve analysis for selected genes. Finally, single-sample gene set enrichment analysis (ssGSEA) was carried out to examine immune cell infiltration in IBS and PCOS. RESULTS: MR analysis identified a causal effect of PCOS on IBS (IVW, OR = 1.034, 95% CI: 1.003-1.065, P = 0.029). Conversely, no relationship between IBS and PCOS was observed in the reverse analysis. Furthermore, integrative bioinformatics and machine learning analyses identified CD14 and CASP1 as key diagnostic biomarkers for both IBS and PCOS, which were significantly associated with immune cell infiltration. CONCLUSION: MR analysis has demonstrated a significant positive causal relationship between PCOS and IBS, though the reverse causality from IBS to PCOS appeared non-significant. The genes CD14 and CASP1 emerged as potential shared diagnostic markers between these two conditions.

Polycystic Ovary Syndrome↗

PubMed2026

Integrated multi-omics identification of m6A-SNP-related diagnostic biomarkers in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) lacks reliable and minimally invasive biomarkers for early diagnosis. m6A-associated single-nucleotide polymorphisms (m6A-SNPs) may influence RNA methylation and gene expression, offering opportunities to identify clinically relevant diagnostic markers. METHODS: We integrated eQTLGen cis-eQTL data, RMVar m6A-SNP annotations, and ALS transcriptomic datasets to identify m6A-SNP-related genes. Random Forest and LASSO regression were combined to screen robust diagnostic markers. A nomogram was constructed and validated using independent cohorts. Immune infiltration, predicted m6A modification sites, and potential RBP-SNP interactions were assessed. Peripheral blood samples from ALS patients were used for exploratory validation of gene expression and global m6A levels. RESULTS: We identified 109 ALS-associated m6A-SNP-related genes with cis-eQTL signals and narrowed these to seven candidate diagnostic markers (TMED5, OXR1, BRI3, FEM1C, SUZ12, EIF2AK4, and TJAP1). The seven-gene model outperformed the individual markers in the training cohort and retained moderate discrimination in the independent validation cohort. ALS samples showed differences in inferred immune-cell composition, including monocytes, neutrophils, and T-cell subsets. The selected SNP loci were located near predicted m6A sites and annotated RBP-binding regions. Exploratory clinical validation showed significant upregulation of FEM1C and SUZ12 at both mRNA and protein levels, accompanied by reduced global m6A modification. CONCLUSIONS: Through multi-omics integration and exploratory clinical validation, this study identifies m6A-SNP-related candidate markers associated with ALS. The findings support further evaluation of m6A-related signatures for ALS discrimination and molecular characterization, while larger independent cohorts and additional calibration are required before clinical application.

Humans↗

PubMed2026

Predicting diagnostic gene biomarkers associated with immune infiltration in patients with diabetes.

Diabetes is a global public health problem with various complications, which can lead to disability and mortality. This study identified potential diagnostic markers for diabetes and explored the immunometabolic mechanisms in the pathological process. The gene expression of 17 diabetes cases and 16 normal controls were obtained from the Gene Expression Omnibus (GEO) database. The "limma" package was employed for screening differentially expressed genes (DEGs). Gene functions and enriched pathways of DEGs were analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Candidate key genes were screened using the least absolute shrinkage and selection operator (LASSO) regression model and support vector machine recursive feature elimination (SVM-RFE) analysis. The diagnostic effectiveness of identified markers was further verified via the receiver operating characteristic (ROC) curve. The compositional patterns of immune cell infiltration and signaling pathway enrichment associated with key genes were explored via single sample Gene Set Enrichment Analysis (ssGSEA) and GSEA analysis, respectively. Possible miRNAs interacting with key genes were predicted via miRcode database. B2M, FTL, SH3BGRL3, and SOD2 were recognized as diagnostic markers for diabetes based on LASSO regression and the support vector machine recursive feature elimination (SVM-RFE) feature selection algorithm. Analysis of immune cell infiltration demonstrated that the four key genes were related to B cells, neutrophils, macrophages, and CD8+ T cells. The diagnostic value of B2M, FTL, and SOD2 for diabetes was higher than that of SH3BGRL3 according to the ROC curve. Validation experiments indicated that the mRNA expression of B2M and FTL was increased in liver tissues of diabetic mice. B2M and FTL can act as diagnostic markers for diabetes and contribute to new understandings of the disease's molecular mechanisms.

Humans↗

PubMed1978

Immunology, tumor markers, and breast cancer.

Although our knowledge of immunologic processes in breast cancer is still inadequate, many preliminary studies described here may yield valuable information after long-term patient follow-up. At present, there is no specific tumor marker diagnostic of breast cancer, but markers such as CEA, ferritin, immune complexes, and specially estrogen receptors have strong potential as prognostic indicators. As a group, breast cancer patients, as do those with other malignancies, demonstrate reduced immunologic capacity, therefore assays of nonspecific immune function may not be relevant. Assays of "specific" reactivity to breast tumor antigens, however, warrant further investigation as clinical tools. Application of immunotherapy to breast cancer is relatively recent and few trials have more than preliminary data. Determination of estrogen receptors should be included in future clinical immunotherapy protocols so that true evaluation of immunologic responses may benefit, hopefully, from our awareness of the endocrine milieu.

Antigens, Neoplasm↗

PubMed2026

Identification and characterization of PsFwC9 conferring Fusarium wilt resistance in pea.

Pea (Pisum sativum L.) is one of the most important edible legumes in China, with both planting area and total yield ranking among the highest in the world. Fusarium wilt, caused by Fusarium oxysporum f. sp. pisi (Fop), is a severe factor limiting pea production. The deployment of resistant pea cultivars is the most effective and sustainable strategy for controlling this disease. In the present study, a novel resistance gene PsFwC9, conferring resistance to Fop race 5, was identified in the resistant pure line Chengwan 9-8 (CW9-8), and its candidate gene Psat4g213640 was characterized and functionally validated to be associated with disease resistance. Genetic analysis of the F₂ population derived from the cross between the resistant parent CW9-8 and the susceptible parent Chengwan 9-1 (CW9-1) revealed that PsFwC9 was controlled by a single dominant gene. Based on whole-genome resequencing, bulked segregant analysis sequencing (BSA-seq) and fine mapping, PsFwC9 was localized to an 817.06-kb region on chromosome 4 (i.e. linkage group IV, chr4LG4), flanked by KASP markers A016508 and A016511, and co-segregated with four markers. Haplotype analysis revealed that only the marker A016615 was significantly associated with Fusarium wilt resistance, and this marker was designated as a diagnostic marker for PsFwC9. Marker A016615 was located at 425 699 725 bp on chr4LG4, corresponding to the 277 bp within Psat4g213640, where a 'A/G' single-nucleotide polymorphism caused an amino acid substitution leading to an alteration in protein structure; therefore, Psat4g213640 was identified as the PsFwC9 candidate gene. Quantitative real-time PCR analysis showed no significant difference in the expression levels of Psat4g213640 between CW9-8 and CW9-1. Overexpression of the candidate gene Psat4g213640CW9-8 in the hairy root system significantly enhanced the resistance of CW9-1 to Fusarium wilt, whereas RNA interference-mediated silencing of Psat4g213640CW9-8 reduced the resistance of CW9-8, indicating that Psat4g213640CW9-8 played a crucial role in pea resistance to Fusarium wilt. In addition, subcellular localization showed that the protein encoded by Psat4g213640 was targeted to the endoplasmic reticulum. Collectively, these findings not only enriched the gene resources for disease resistance in pea and provided an important foundation for elucidating the molecular mechanism of PsFwC9-mediated resistance, but also provided important technical support for the practical application of molecular breeding for disease resistance in pea.

Journal Article↗

PubMed2025

Discovery of novel diagnostic biomarkers of hepatocellular carcinoma associated with immune infiltration.

OBJECTIVE: Diagnosis of hepatocellular carcinoma (HCC) remains challenging for clinicians. Machine learning approaches and big data analyses are viable strategies for identifying HCC diagnostic markers. MATERIALS AND METHODS: In this study, we downloaded mRNA expression profiles of HCC from the GEO database and used random forest and machine learning algorithms, such as least absolute shrinkage and selection operator, to screen for reliable diagnostic genes. Disease Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis enrichment analyses were performed to explore differential gene functions and disease pathways. CIBERSORT was performed to calculate the immune cell infiltration of HCC and the correlation between diagnostic genes and immune cells. Cell experiments were performed to evaluate the function of R-spondin 3 (RSPO3) in HCC cells. Immunohistochemical staining was used to evaluate the protein expression of CD138, CD206 and iNOS. RESULTS: The results indicated that extracellular matrix protein 1 (ECM1), Niemann-Pick C1-Like 1 (NPC1L1) and RSPO3 were down-regulated in HCC compared with the normal group (p < 0.05), which was validated in clinical tissue samples. Moreover, ECM1, NPC1L1 and RSPO3 had high diagnostic values (AUC > 0.75) for HCC in both training and test groups. Immuno-infiltration analysis revealed that ECM1 and RSPO3 were highly positively correlated with neutrophil and macrophage M2 levels, whereas they were negatively correlated with Tregs. RSPO3-si affected cell proliferation and apoptosis in HCC. Furthermore, RSPO3 exhibited a positive correlation with tumour progression, the proportion of plasma cells and M2 macrophages in mice, while showing a negative association with M1 macrophages. CONCLUSION: The present study identified ECM1, NPC1L1 and RSPO3 as new diagnostic biomarkers for HCC based on normal and diseased samples from HCC, meanwhile the pro-oncogenic function of RSPO3 and its regulation on immune infiltration have been confirmed.

Carcinoma, Hepatocellular↗

PubMed1979

Human endodermal sinus tumour in nude mice and its markers for diagnosis and management.

Two human endodermal sinus tumours (yolk sac tumours) were transplanted successfully into nude mice. The transplanted tumours maintained not only morphological characters, such as Schiller-Duval bodies, but also the ability to synthesise alpha-fetoprotein, lactic dehydrogenase 1, liver and bone type alkaline phosphatase, and some human serum proteins. Since these tumours produced lactic dehydrogenase 1 but not the other four isozymes of lactic dehydrogenase, this isozyme, like alpha-fetoprotein, seems to be a good marker for the diagnosis and management of cases of endodermal sinus tumour. One of the two tumours produced another fetal antigen or carcinoembryonic antigen in addition to alpha-fetoprotein. These two endodermal sinus tumours, with their various markers in nude mice, will be useful in studies on diagnostic markers.

Alkaline Phosphatase↗

PubMed1979

Mammalian endogenous peroxidases as cellular markers and as biosynthetic endpoints of hormone-mediated activity: viewpoint from cytochemistry.

Aldehyde-resistant, diaminobenzidine-stained endogenous peroxidases form ideal markers for the biochemical endpoints of hormone stimulation and differentiation of certain mammalian cells and tissues. The lactoperoxidase (LPO)-type of endogenous peroxidases are synthesized by the acinar cells of the salivary, Harderian, lacrimal and mammary glands and are present in their secretions. These LPO-type enzymes, that are inhibited by cyanide and aminotriazole, appear to operate extracellularly as bactericidal agents in milk and in other biological fluids. In the mammary gland, lactoperoxidase is a consistent marker enzyme for differentiated acinar cells engaged in lactogenesis. Myeloperoxidase (MPO)-type endogenous peroxidases are prominent markers for the GERL endomembrane system and differentiated lysosomes in certain cells of the reticuloendothelial system and phagocytes. MPO is prominent within eosinophils, peritoneal macrophages and in Kupffer cells. The MPO-type endogenous peroxidases function primarily within lysosomes as bactericidal agents. Thyroid peroxidase (TPO) is relegated to the cisternae of the granular endoplasmic reticulum and Golgi apparatus, to apical cytoplasmic vesicles and to the luminar cell membrane surface of acinar cells. The enzyme is probably activated at release and functions both in the organification reaction (T leads to To) and in the biosynthesis of thyroxine. Thyroid stimulating hormone (TSH) appears to play a key role in the regulation of TPO levels and activity in the thyroid gland. Certain tissues displaying growth-dependency on estrogen (i.e., uterus, cervix, vagina and the DMBA-induced rat mammary tumor) synthesize and secrete endogenous peroxidase into their lumina. These enzymes serve as important marker proteins of estrogen action, in that they occur distal to the binding of estrogen to its receptor protein. Estrogen antagonists, particularly CI-628 (Parke-Davis) and Nafoxidine (Upjohn) that appear to function through the estrogen receptor mechanism, also induce synthesis of the reproductive tract endogenous peroxidase but inhibit growth of these tissues. Progesterone antagonizes the synthesis of the reproductive tract peroxidases and inhibits growth of the tissues as well, in part, through the reduction of the cytosol estrogen receptor protein. Endogenous peroxidase activity appears to represent a reliable marker for rodent breast cancer tissues displaying dependency for estrogen and is of potential interest as a diagnostic marker protein in human breast cancer. Rat uterine peroxidase (UP) has been investigated by microelectrophoretic techniques. The molecular weight of UP has been determined in the range of 100,000 by using polyacrylamide gradient gels in the absence and presence of nonionic and anionic detergents. The isoelectric point of UP is located between pH 4.5 and 5.9. Employing the two-dimensional combination of isoelectric focusing and gel gradient electrophoresis, UP was separated into two subunits, one having a molecular weight of 70,000, the other less than 20,000.

Animals↗

PubMed2025

Diversity of Salmonella enterica isolates from urban river and sewage water in Blantyre, Malawi.

BACKGROUND: Salmonella enterica encompasses over 2,600 serovars, including several commonly associated with severe infection in humans. Salmonella is a major cause of sepsis in Africa; however, diagnosis requires clinical microbiology facilities. Environmental surveillance has the potential to play a role in Salmonella surveillance. METHODS: We undertook water-based environmental surveillance in Blantyre, Malawi, from 2018-2020, taking samples from rivers (87.9%), a sewage plant (8.85%) and other water sources (3.24%), isolating and storing 1,042 non-typhoidal Salmonella (NTS) isolates in this period. Of these, 341 NTS isolates were whole genome sequenced, genome quality was checked, duplicate genomes from any given sample were removed and core genome phylogeny was reconstructed. AMRFinder, PathogenWatch and SISTR were used to further investigate serovar, sequence type and antimicrobial resistance determinants. RESULTS: After quality checks, and removal of duplicate genomes, 270 NTS genomes remained for further analysis. Multiple Salmonella serovars associated with human infection were detected, of which S. Typhimurium (55/270 isolates) was the most common, including 44 of Sequence Type (ST) 313, a serovar commonly associated with severe invasive disease (iNTS). Six lineage 2 ST313 genomes possessed AMR genes predicting multidrug resistance (MDR), while 29 lineage 3 isolates contained no AMR predictive genes. PCR based detection of staG has been proposed as a diagnostic marker of S. Typhi; however, all eight genomes that contained staG identified as Salmonella enterica serovar Orion, raising concerns about the specificity of this marker as a monoplex for environmental surveillance of S. Typhi. DISCUSSION: The study identified diverse Salmonella serovars in the environment, including those reported to cause invasive disease, emphasizing the complex but potentially valuable contribution of implementing environmental surveillance for Salmonella in high burden areas lacking diagnostic microbiology capacity.

Sewage↗

PubMed2024

LINC00887 promotes GCN5-dependent H3K27cr level and CRC metastasis via recruitment of YEATS2 and enhancing ETS1 expression.

Recent observations have revealed upregulation of H3K27cr in colorectal cancer (CRC) tissues; however, the underlying cause remains elusive. This study aimed to investigate the mechanism of H3K27cr upregulation and its roles in CRC metastasis. Clinically, our findings showed that H3K27cr served as a highly accurate diagnostic marker to distinguish CRC tissues from healthy controls. Elevated levels of LINC00887 and H3K27cr were associated with a poorer prognosis in CRC patients. Functionally, LINC00887 and H3K27cr facilitated the migration and invasion of CRC cells. Mechanistically, LINC00887 interacted with SIRT3 protein. Overexpressed of LINC00887 obstructed the enrichment of SIRT3 within GCN5 promoter, thereby elevating H3K27ac but not H3K27cr level within this region, subsequently activating GCN5 expression. This activation increased the global level of H3K27cr, promoting the enrichment of GCN5, H3K27cr, and YEATS2 within ETS1 promoter, activating ETS1 transcription and ultimately promoting the metastasis of CRC. The in vivo study demonstrated that inhibition of LINC00887 suppressed CRC metastasis, but this inhibitory effect was nullified when mice were treated with NaCr. In conclusion, our results confirmed the diagnostic biomarker potential of H3K27cr in individuals with CRC, and proposed a functional model to elucidate the involvement of LINC00887 in promoting CRC metastasis by elevating H3K27cr level.

Humans↗

PubMed2026

Plasma proteins are integral to cross-tissue gene regulatory networks implicated in cardiometabolic disorders and coronary artery disease.

The plasma proteome has demonstrated promise for identifying diagnostic markers for cardiometabolic disorders (CMDs) and coronary artery disease (CAD). However, identifying the organ of origin for these biomarkers is critical for establishing biological relevance. We performed a multi-omic integrative analysis across multiple tissues from the STARNET study by profiling 974 plasma proteins in 532 CAD patients, integrating RNA sequencing (RNA-seq) data from the arterial wall, major metabolic organs, and blood. We identified 144 cis-protein quantitative trait loci in plasma, colocalizing with tissue cis-expression quantitative trait loci. Additionally, by mapping tissue mRNA "seed genes," we traced 262 plasma proteins to their source organs, primarily the liver. Crucially, we found that 851 plasma proteins are associated with the activity of cross-tissue gene regulatory networks (GRNs), including GRNs implicated in CMD and CAD development. Our findings demonstrate that plasma proteins are integral components of GRNs, with potential for developing reliable diagnostics and precise therapeutic targets. A record of this paper's transparent peer review process is included in the supplemental information.

cardiometabolic disorders↗

PubMed1979

Elevation of brain-type creatine kinase in serum from patients with carcinoma.

The brain isoenzyme of creatine kinase (CK BB) occurs in trace amounts in normal serum and is moderately increased in only a small number of non-oncological conditions. Although many tissues and tumors contain CK BB, we observed serum elevations only in certain carcinomas. Eleven patients with tissue-proven small cell anaplastic carcinoma (SCAC) of the lung had striking elevations of serum CK BB and no evidence of central nervous system (CNS) metastases. Significant increases were also observed in three cases of prostatic carcinoma with no apparent CNS involvement, and in one case each of adenocarcinoma and SCAC of the lung with proven CNS metastases. Three patients with SCAC of lung without distant metastases, three with SCAC of the esophagus with distant metastases but no known CNS involvement, and 17 patients with oncological conditions other than SCAC of the lung or adenocarcinoma of the prostate have failed to show elevation in serum CK BB activity. Serum CK BB may be useful as a diagnostic marker or indicator of metastases for some carcinomas.

Adenocarcinoma↗

PubMed2026

Cribriform tumors of the skin: CD38 expression distinguishes from histologic mimics in a multi-institutional series.

Cribriform tumor of the skin (formerly primary cutaneous cribriform carcinoma/primary cutaneous cribriform apocrine carcinoma) is a rare adnexal neoplasm of uncertain malignant potential. Recent studies have identified recurrent co-deletion of the long arm of chromosomes 6 and 9 and CD38 overexpression as potential diagnostic features, but their sensitivity and specificity remain incompletely defined. We identified 11 cribriform tumors with classic morphologic features, including several previously reported molecular characterized cases and additional unpublished cases, from multiple institutions. CD38 immunohistochemistry was performed on all tumors and compared with a panel of morphologic mimics, including adenoid cystic carcinoma (n = 8), digital papillary adenocarcinoma (n = 8), eccrine/apocrine adenomas (n = 7), hidradenoma (n = 2), and endocrine mucin-producing sweat gland carcinoma (n = 3). SNP array analysis was available in nine cases. Patients had a median age of 47 years with a slight female predominance (64%). Tumors commonly involved the extremities and ranged from 0.3 to 2.0 cm. Histologically, all cases demonstrated a well-circumscribed dermal neoplasm of bland epithelial cells arranged in cribriform architecture with characteristic thread-like intraluminal bridging, without high-grade features. CD38 expression was identified in 9/11 cases (82%), typically with moderate-to-strong diffuse cytoplasmic staining. All morphologic mimics (n = 28) were CD38 negative. Recurrent chromosomal deletions involving 6q and/or 9q were identified in 7/8 (88%) successfully tested cases. Two morphologically classic cribriform tumors lacked CD38 expression, including one with confirmed 6q/9q codeletion, while one CD38-positive case lacked detectable genomic copy number alterations. These findings further support cribriform tumors as a molecularly distinct, low-grade adnexal neoplasm characterized by recurrent 6q/9q deletions and frequent CD38 expression. CD38 appears to be a useful adjunctive diagnostic marker with high specificity among the selected mimics tested, although its sensitivity is incomplete, and absence of staining does not exclude the diagnosis.

Adnexal tumors↗