TMPRSS4 Expression Predicts Survival and Benefit from Neoadjuvant Chemotherapy in Pancreatic Cancer

Transmembrane serine protease 4 (TMPRSS4) is known to promote epithelial-mesenchymal transition, invasion, and metastasis in pancreatic cancer and has been linked to chemotherapy resistance. However, whether TMPRSS4 status affects the efficacy of neoadjuvant chemotherapy (NAC) in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study aimed to evaluate the clinical significance of TMPRSS4 expression in patients with resected PDAC, focusing on its prognostic impact and interaction with NAC.

This retrospective study included consecutive patients who underwent curative-intent resection for PDAC between November 2015 and October 2024. Expression of TMPRSS4 was assessed immunohistochemically. The study examined its associations with clinicopathologic factors, survival, and NAC efficacy.

Among 154 patients screened, the study included 152 patients with evaluable TMPRSS4 expression. In 95 patients (63 %), TMPRSS4 expression was positive. The TMPRSS4-positive tumors were significantly larger than the TMPRSS4-negative tumors. The 5-year overall survival rate was significantly lower in the TMPRSS4-positive group than in the TMPRSS4-negative group. Larger tumor size, TMPRSS4 positivity, lymph node metastasis, and non-adjuvant chemotherapy were independently associated with poor overall survival. Among the patients with resectable PDAC (n = 119), NAC significantly improved survival for the TMPRSS4-positive patients, whereas no significant benefit was observed for the TMPRSS4-negative patients. A significant interaction was observed between TMPRSS4 expression and NAC (hazard ratio, 0.25; 95 % confidence interval, 0.07-0.88; p = 0.032).

In PDAC, TMPRSS4 expression was associated with poor prognosis. The survival benefit of NAC appeared to be greater for the TMPRSS4-positive patients, suggesting that TMPRSS4 may serve as a potential exploratory marker for treatment stratification.