Published online Oct 14, 2019. doi: 10.3748/wjg.v25.i38.5814
Peer-review started: June 3, 2019
First decision: July 21, 2019
Revised: August 16, 2019
Accepted: September 13, 2019
Article in press: September 13, 2019
Published online: October 14, 2019
Gastric cancer (GC) is the most prevalent gastrointestinal tract malignancy. The prognosis of GC patients remains relatively poor. Through bioinformatics data mining and integrated analysis, we found that Wnt1-inducible signaling pathway protein 1 (WISP1) mRNA was upregulated in GC tissues relative to normal gastric tissues. However, it needs to be further verified clinically.
There are insufficient reports about the correlation between WISP1 and GC.
The aim of the present study was to explore the expression pattern and clinical significance of WISP1 in GC.
Public data portals, including Oncomine, the TCGA database, COEXPEDIA, and Kaplan-Meier plotter were analyzed for the expression and clinical significance of WISP1 mRNA levels in GC. One hundred and fifty patients who underwent surgery for GC between February 2010 and October 2012 at the Affiliated Hospital of Jiangnan University were selected for validation study. WISP1 expression was measured at both the mRNA and protein levels by RT-qPCR, Western blot analysis, and immunohistochemistry (IHC). 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. IC50 was detected by CTB assay.
WISP1 expression at both the mRNA and protein levels was 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, distant metastasis, age, sex, 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. The IC50 of oxaliplatin in MKN45 and AGS cell lines were significantly reduced after WISP1 knock-down. In addition, WISP1 knock-down enhanced γH2AX expression and reduced XRCC1 expression.
WISP1 is overexpressed in GC tissues and is associated with a poor prognosis, indicating its potential as a novel prognosis biomarker for GC. Mechanistically, knock-down of WISP1 expression enhances oxaliplatin sensitivity by reducing DNA repair and enhancing DNA damage. WISP1 may be a potential therapeutic target for GC treatment.
The present study suggested that WISP1 is a novel prognostic biomarker for GC, and the significance of WISP1 as a promising therapeutic target for GC is highlighted.