Multi-omics analysis of TMED3 as a potential prognostic biomarker across six cancer types
image: Panels a–f correspond to BLCA, HNSC, KIRC, KIRP, LIHC, and LUAD, respectively; each panel shows normal tissue on the left and corresponding cancer tissue on the right. The staining category reported by HPA is shown beneath each image. Images were obtained from the Human Protein Atlas and are presented for comparative, semi-quantitative assessment. BLCA, bladder cancer; HNSC, head and neck squamous cell carcinoma; HPA, Human Protein Atlas; IHC, immunohistochemistry; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma.
Credit: Lan Chen
Background and objectives
The clinical and genetic characteristics of TMED3, a p24-family protein, across different cancer types remain incompletely understood. This study aimed to evaluate its expression patterns, prognostic relevance, epigenetic regulation, immune associations, genetic alterations, functional networks, and chemical-gene interactions across six cancer types.
Methods
Public, de-identified data from UALCAN, GENT2, the Human Protein Atlas (HPA), Kaplan-Meier Plotter, MEXPRESS, cBioPortal, TIMER2.0, the Comparative Toxicogenomics Database (CTD), STRING, and DAVID were analyzed. The clinical and genetic characteristics of TMED3 in bladder cancer (BLCA), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), and lung adenocarcinoma (LUAD) were analyzed. Database-reported nominal P-values were used because unified multiple-testing correction was not feasible.
Results
In UALCAN analysis, TMED3 mRNA was upregulated in BLCA, KIRP, LIHC, KIRC, and LUAD and downregulated in HNSC. HPA data showed higher TMED3 protein expression in BLCA, HNSC, and LUAD. Kaplan-Meier Plotter analysis showed that higher TMED3 expression was associated with shorter overall survival in HNSC, KIRC, KIRP, LIHC, and LUAD, but not in BLCA, and was not significantly associated with recurrence-free survival in any of the six cancers. MEXPRESS analysis suggested an inverse association between promoter methylation and TMED3 expression. TIMER analysis showed negative correlations between TMED3 expression and CD8+ T-cell infiltration in BLCA, HNSC, and LUAD, but a positive correlation in LIHC. cBioPortal showed low TMED3 alteration frequencies across the six cancers, and STRING and DAVID analyses linked TMED3-associated genes mainly to endoplasmic reticulum-Golgi trafficking and vesicle-mediated transport pathways. CTD analysis identified azacitidine, doxorubicin, and MK-2206 as chemicals associated with altered TMED3 expression.
Conclusions
TMED3 is a cancer-type-specific prognostic candidate associated with shorter OS in HNSC, KIRC, KIRP, LIHC, and LUAD. Protein-level evidence shows higher expression in BLCA, HNSC, and LUAD, while promoter methylation and CD8+ T-cell correlations provide testable regulatory and tumor microenvironment-related hypotheses. Because the analyses relied on database-reported nominal P-values without unified multiple-testing correction and lacked experimental validation, these findings establish TMED3 as a priority candidate for independent mechanistic and clinical validation rather than a clinically validated biomarker or therapeutic target.
Full text
https://www.xiahepublishing.com/2996-3427/OnA-2026-00003
The study was recently published in the Oncology Advances.
Oncology Advances is dedicated to improving the diagnosis and treatment of human malignancies, advancing the understanding of molecular mechanisms underlying oncogenesis, and promoting translation from bench to bedside of oncological sciences. The aim of Oncology Advances is to publish peer-reviewed, high-quality articles in all aspects of translational and clinical studies on human cancers, as well as cutting-edge preclinical and clinical research of novel cancer therapies.
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