Up-regulated Wnt1-inducible signaling pathway protein 1 correlates with poor prognosis and drug resistance by reducing DNA repair in gastric cancer

作者：Lihua Zhang, Yan Wang, Qianqian Fan, Yankui Liu, Longhai Li, Xiaowei Qi, Yong Mao, Hua Dong · 发表于：World Journal of Gastroenterology · 年份：2019 · DOI：10.3748/wjg.v25.i38.5814 · 被引用次数：25 · 研究领域：Connective Tissue Growth Factor Research、Wnt/β-catenin signaling in development and cancer、Liver physiology and pathology

BACKGROUND: Wnt1-inducible signaling pathway protein 1 (WISP1) is upregulated in several types of human cancer, and has been implicated in cancer progression. However, its clinical implications in gastric cancer (GC) remain unclear. AIM: To explore the expression pattern and clinical significance of WISP1 in GC. METHODS: expression of WISP1 in the GC tissues was determined by IHC, and the patients were accordingly classified into high- and low-expression groups. The correlation of WISP1 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses. WISP1 was knocked down by RNA interference. The 50% inhibitory concentration of oxaliplatin was detected by CellTiter-Blue assay. RESULTS: WISP1 levels at both the mRNA and protein levels were remarkably upregulated in GC tissues compared to normal tissues. Moreover, IHC revealed that WISP1 expression was associated with T stage and chemotherapy outcome, but not with lymph node metastasis, age, gender, histological grade, or histological type. GC patients with high WISP1 expression showed a poor overall survival. Multivariate survival analysis indicated that WISP1 was an important prognostic factor for GC patients. Mechanistically, knock-down of WISP1 expression enhanced sensitivity to oxaliplatin by reducing DNA repair and enhancing DNA damage. CONCLUSION: Significantly upregulated WISP1 expression is associated with cancer progression, chemotherapy outcome, and prognosis in GC...