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Effects of transmembrane serine protease 4 on the survival in patients with pancreatic ductal adenocarcinoma undergoing surgery followed by adjuvant chemotherapy

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Abstract

Purpose

The transmembrane serine protease 4 (TMPRSS4) gene is upregulated in various human cancers. However, its biological functions in pancreatic ductal adenocarcinoma remain unclear. We examined the expression of TMPRSS4 in pancreatic ductal adenocarcinoma tissues and its correlation with clinicopathological parameters in patients with pancreatic ductal adenocarcinoma who underwent surgery.

Methods

The TMPRSS4 expression was immunohistochemically examined in 81 PDAC patients with pancreatic ductal adenocarcinoma. We analyzed the association between the TMPRSS4 expression and clinicopathological factors, the recurrence-free survival (RFS), and the overall survival (OS) and examined the effect of TMPRSS4 expression on cell migration and sensitivity to 5-fluorouracil.

Results

The expression rate of TMPRSS4 in the samples was 62.9% (51/81). The TMPRSS4 expression was not correlated with any clinicopathological feature. The five-year overall and recurrence-free survival rates were significantly lower in the TMPRSS4-positive group than in the TMPRSS4-negative group. On a multivariate analysis, TMPRSS4 positivity, poorly differentiated histology, and non-adjuvant chemotherapy predicted a poor OS, while TMPRSS4 positivity and poorly differentiated histology predicted a poor RFS. TMPRSS4-silenced pancreatic ductal adenocarcinoma cells showed higher sensitivity to 5- fluorouracil than did the control siRNA-transfected cells.

Conclusions

TMPRSS4 can be considered a prognostic factor and therapeutic target for pancreatic ductal adenocarcinoma.

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Abbreviations

TMPRSS4:

Transmembrane serine protease 4

PDAC:

In pancreatic ductal adenocarcinoma

5-FU:

5-Fluorouracil

siControl:

Control siRNA

FdUMP:

Fluorodeoxyuridine monophosphate

TS:

Thymidylate synthase

FBS:

Fetal bovine serum

OS:

Overall survival

RFS:

Recurrence-free survival

NCCN:

National Comprehensive Cancer Network

EMT:

Epithelial-to-mesenchymal transition

SDS:

Sodium dodecyl sulfate

PSM:

Propensity score matching

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Authors and Affiliations

  1. Department of Surgery, Kure Medical Center/Chugoku Cancer Center, National Hospital Organization, 3-1, Kure, Hiroshima, 737-0023, Japan

    Sho Tazuma, Takeshi Sudo, Yoshiyuki Shibata & Hirotaka Tashiro

  2. Department of Diagnostic Pathology, Kure Medical Center/Chugoku Cancer Center, National Hospital Organization, 3-1, Kure, Hiroshima, 737-0023, Japan

    Akira Ishikawa & Kazuya Kuraoka

  3. Department of Gastroenterology, Kure Medical Center/Chugoku Cancer Center, National Hospital Organization, 3-1, Kure, Hiroshima, 737-0023, Japan

    Atsushi Yamaguchi

  4. Institute for Clinical Laboratory, Kure Medical Center/Chugoku Cancer Center, National Hospital Organization, 3-1, Aoyama, Kure, Hiroshima, 737-0023, Japan

    Yuko Ishida

  5. Department of Surgery, Graduate School of Biochemical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan

    Kenichiro Uemura & Shinya Takahashi

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  1. Sho Tazuma
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Correspondence to Hirotaka Tashiro.

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Sho Tazuma and other co-authors have no conflicts of interest.

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Tazuma, S., Sudo, T., Ishikawa, A. et al. Effects of transmembrane serine protease 4 on the survival in patients with pancreatic ductal adenocarcinoma undergoing surgery followed by adjuvant chemotherapy. Surg Today (2024). https://doi.org/10.1007/s00595-024-02824-y

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