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  • TMPRSS15 in Esophageal Carcinoma: A Comprehensive Bioinformatic Analysis of Expression, Diagnostic Value, Prognosis, and Genomic Alterations

  • Fatemeh darvish,1,* Alale jahanpor,2 Mehdi jafari,3
    1. Department of Biochemistry and Biophysics » School of medicine, Golestan University of Medical Sciences » Gorgan, Iran
    2. Department of Biochemistry and Biophysics » School of medicine, Golestan University of Medical Sciences » Gorgan, Iran
    3. Department of Biochemistry and Biophysics » School of medicine, Golestan University of Medical Sciences » Gorgan, Iran


  • Introduction: TMPRSS15 (enteropeptidase) is a serine protease primarily involved in intestinal protein digestion. However, its expression pattern and potential clinical significance in esophageal carcinoma (ESCA) remain poorly characterized. This study aimed to investigate the expression profile, diagnostic value, prognostic significance, and genomic alteration landscape of TMPRSS15 in ESCA using publicly available bioinformatics databases.
  • Methods: Differential expression of TMPRSS15 between tumor and normal esophageal tissues was analyzed using TNMplot with the Mann–Whitney U test. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic ability of TMPRSS15 expression to discriminate tumor from normal tissue. The association between TMPRSS15 expression and tumor stage was assessed using GEPIA2 with one-way analysis of variance (ANOVA). Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan–Meier analysis in GEPIA2 based on the median expression cutoff. Genomic alterations, including mutations, amplifications, and deep deletions, and their associations with survival outcomes were investigated using cBioPortal based on the TCGA PanCancer Atlas dataset (n=182).
  • Results: TMPRSS15 expression was significantly lower in tumor tissue than in normal tissue (median: 23 vs. 33.5; fold change=0.69, p=1.12×10⁻⁴). ROC analysis demonstrated limited-to-moderate diagnostic discrimination, with an area under the curve (AUC) of 0.66. A non-significant trend toward increased TMPRSS15 expression was observed with advancing tumor stage (F=2.26, p=0.0835). No significant association was observed between TMPRSS15 expression and OS (log-rank p=0.79, HR=0.94) or DFS (log-rank p=0.58, HR=1.10). Genomic analysis identified TMPRSS15 alterations in approximately 4–7% of patients, predominantly deep deletions, together with amplifications and one missense mutation (T685M; variant of uncertain significance) located within the trypsin domain. Genomic alteration status was not significantly associated with survival outcomes (all p>0.6).
  • Conclusion: TMPRSS15 was significantly downregulated in esophageal tumor tissue compared with normal tissue and demonstrated limited-to-moderate diagnostic discrimination (AUC=0.66). The presence of recurrent genomic alterations, particularly deep deletions, suggests genomic dysregulation of TMPRSS15 in ESCA; however, its expression and alteration status showed limited prognostic value. Further experimental and clinical validation is warranted.
  • Keywords: TMPRSS15; Enteropeptidase; Esophageal Carcinoma Gene Expression

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