Wang Fei, Hu Yi-Lin, Feng Ying, Guo Yi-Bing, Liu Yi-Fei, Mao Qin-Sheng, Xue Wan-Jiang
Department of Gastrointestinal Surgery, The Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
J Surg Oncol. 2019 Jun;119(8):1108-1121. doi: 10.1002/jso.25448. Epub 2019 Mar 25.
Serine protease-3 (PRSS3) is a known contributor to the genesis and development of malignant tumors, although its role in gastric cancer (GC) is still unclear.
PRSS3 expression in GC tissue samples and its relationship with clinicopathological features were analyzed. Effects of GC cellular responses to the introduction of small interfering RNA (siRNA)-mediated and short hairpin RNA (shRNA)-mediated interference with tumor PRSS3 expression were also assessed.
PRSS3 was significantly upregulated in GC tissues, and PRSS3 protein levels were higher in tumors that developed metastases soon after the surgery compared with those that remained metastasis-free. High expression of PRSS3 was associated with tumor N staging and independently predictive of postoperative prognosis in patients with GC. The V1 variant of PRSS3 was primarily detected in GC tissue and cell lines, the others (V2-V4) being scarcely detectable. Methylation and demethylation drugs had no impact on expression levels of any PRSS3 transcriptional variant. The downregulated PRSS3 expression suppressed GC cell growth, migration, and invasion in vitro and in vivo.
PRSS3 appears to act as an oncogene of GC. High PRSS3 expression portends postoperative metastasis, serving as an effective biomarker of poor therapeutic outcomes.
丝氨酸蛋白酶-3（PRSS3）是已知的恶性肿瘤发生和发展的促成因素，尽管其在胃癌（GC）中的作用仍不清楚。
分析PRSS3在GC组织样本中的表达及其与临床病理特征的关系。还评估了GC细胞对小干扰RNA（siRNA）介导和短发夹RNA（shRNA）介导的肿瘤PRSS3表达干扰的反应效果。
PRSS3在GC组织中显著上调，与术后很快发生转移的肿瘤相比，未发生转移的肿瘤中PRSS3蛋白水平更高。PRSS3的高表达与肿瘤N分期相关，并且可独立预测GC患者的术后预后。PRSS3的V1变体主要在GC组织和细胞系中检测到，其他变体（V2-V4）几乎检测不到。甲基化和去甲基化药物对任何PRSS3转录变体的表达水平均无影响。PRSS3表达下调在体外和体内均抑制了GC细胞的生长、迁移和侵袭。
PRSS3似乎是GC的一种癌基因。PRSS3高表达预示术后转移，是治疗效果差的有效生物标志物。
