Background

Transmembrane serine protease 4 (TMPRSS4) belongs to the family of type II transmembrane serine proteases that are known to be upregulated in many malignant tumors. However, there is a paucity of studies documenting the clinical impact and biological effects of TMPRSS4 on gastric cancer (GC) patients who underwent surgery.

Methods

Tissues samples were obtained from 105 patients with GC who underwent gastrectomy followed by adjuvant chemotherapy, excluding those at stage I. The expression of TMPRSS4 was examined through immunohistochemical analysis. The association between TMPRSS4 expression and clinico-pathological features as well as prognosis was assessed. Moreover, the effects of TMPRSS4 expression on cell migration and sensitivity to 5-FU were investigated.

Results

The expression rate of TMPRSS4 was 56.3% (59/105) in GC cases. The expression of TMPRSS4 was positively correlated with the depth of tumor (T) and venous (V) invasion. The 5-year overall survival (OS) and recurrence-free survival (RFS) rates of the TMPRSS4-positive group was significantly lower than that of the TMPRSS4-negative group (p=0.0001 and p=0.005, respectively). Especially, there was significant differences in OS and RFS of patients with stage III cancer between the two groups (p=0.0064 and 0.012, respectively). Multivariate analysis demonstrated that TMPRSS4 expression and the stage of cancer were crucial prognostic factors for RFS. TMPRSS4-silenced GC cells exhibited increased sensitivity to 5-FU when compared with the non-specific control siRNA-transfected cells.

Conclusion

TMPRSS4 can be considered as a potential prognostic biomarker, especially for stage III, and a promising therapeutic target for GC.

中文翻译：

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TMPRSS4作为胃癌患者预后生物标志物和潜在治疗靶点的效用

背景

跨膜丝氨酸蛋白酶 4 (TMPRSS4) 属于已知在许多恶性肿瘤中上调的 II 型跨膜丝氨酸蛋白酶家族。然而，很少有研究记录 TMPRSS4 对接受手术的胃癌 (GC) 患者的临床影响和生物学效应。

方法

组织样本取自 105 名接受胃切除术和辅助化疗的 GC 患者，不包括 I 期患者。通过免疫组织化学分析检查 TMPRSS4 的表达。评估了 TMPRSS4 表达与临床病理特征以及预后之间的关联。此外，研究了 TMPRSS4 表达对细胞迁移和对 5-FU 敏感性的影响。

结果

TMPRSS4在GC病例中的表达率为56.3%（59/105）。TMPRSS4的表达与肿瘤（T）和静脉（V）浸润深度呈正相关。TMPRSS4阳性组的5年总生存率（OS）和无复发生存率（RFS）显着低于TMPRSS4阴性组（分别为p = 0.0001和p = 0.005）。尤其是两组III期癌症患者的OS和RFS存在显着差异（p= 0.0064 和 0.012，分别）。多变量分析表明，TMPRSS4 表达和癌症分期是 RFS 的关键预后因素。与非特异性对照 siRNA 转染的细胞相比，TMPRSS4 沉默的 GC 细胞对 5-FU 的敏感性增加。

结论

TMPRSS4 可以被认为是一种潜在的预后生物标志物，特别是对于 III 期，以及 GC 的有希望的治疗靶点。