TMPRSS4 as a prognostic biomarker after gastric cancer surgery in a multicenter retrospective study

Transmembrane protease serine 4 (TMPRSS4) is a member of the type II transmembrane serine protease family known to be upregulated in many malignancies. We previously showed that TMPRSS4 may be a prognostic biomarker and therapeutic target for gastric cancer (GC), especially in stage III. In this retrospective study conducted at 10 institutions, all 325 patients underwent R0 resection involving D2 lymph node dissection. TMPRSS4 expression was examined using immunohistochemical analysis. TMPRSS4 expression was upregulated in 44.9% of participants. The 5-year overall survival (OS) of the TMPRSS4-positive group was significantly lower than that of the TMPRSS4-negative group (62.4% vs. 76.4%, respectively; p = 0.0149). Univariate analysis revealed that TMPRSS4 upregulation, tumor size, deeper tumor invasion, lymph node metastasis (N), lymphatic invasion, and tumor stage were significant prognostic factors for OS. Multivariate analysis revealed that N and TMPRSS4 upregulation were significant prognostic factors for OS. The 5-year OS rate was examined in two patient groups: the group with the receiver operating characteristic curve cut-off value ≥ 45% for TS-1 (cancer drug formulation) oral dosage and the group with TS-1 dosage cut-off value < 45%. For the patients in the TS-1 dosage ≥ 45% group, there were significant differences in OS between the TMPRSS4-positive and -negative groups (p = 0.0284): the 5-year OS rates of TMPRSS4-positive and -negative groups were 65.2% and 79.2%, respectively. Our findings suggest that TMPRSS4 overexpression is a useful biomarker for GC, and that an anti-TMPRSS4 antibody may have potential as a novel therapeutic agent.