Di-san junyi daxue xuebao (Nov 2021)
Expression and function of Niemann-Pick disease type C2 protein in gastric cancer
Abstract
Objective To observe the expression profile of Niemann-Pick disease type C2 (NPC2) protein in gastric cancer, analyze its prognostic significance, and explore its regulatory function in the disease. Methods Expression difference of NPC2 in gastric cancer and normal gastric tissue was explored based on the Gene Expression Omnibus (GEO) database (GSE15459, GSE33335, GSE63089, GSE54129, GSE62254 and GSE84437), the Cancer Genome Atlas (TCGA) database and the tissue gastric cancer (GSE15459, GSE33335, GSE63089, GSE54129, GSE62254 and GSE84437) and the tissue chip of gastric cancer. The correlation between the expression of NPC2 and clinicopathological characteristics of gastric cancer was analyzed by contingency table analysis. Kaplan-Meier survival analysis and multivariate Cox regression analysis were performed to explore the prognostic significance of NPC2 expression in the cancer. The possible molecular mechanism of NPC2 regulating gastric cancer was analyzed by gene set enrichment analysis (GSEA). Transwell assay was carried out to measure the migration ability of gastric cancer cell line SGC7901 after down-regulation of NPC2. Results NPC2 was highly expressed in gastric cancer (GSE33335: 7.917±0.077 vs 7.601±0.074, P=0.009 6; GSE63089: 9.083±0.123 vs 8.435±0.148, P=0.000 1; the tissue chip: 4.596±0.230 vs 3.336±0.176, P < 0.000 1). Its expression level was correlated to the clinical stage of American Joint Committee on Cancer (AJCC) (GSE15459: P=0.009; the tissue chip: P=0.04) and number of nearby lymph nodes (pN, the tissue chip: P=0.04). Gastric cancer patients with high NPC2 level had a poor prognosis (TCGA: P < 0.0001; GSE15459: P=0.002 3; the tissue chip: P=0.0032), and the protein was an independent prognostic predictor of gastric cancer (TCGA: HR=2.140, 95%CI: 1.523~3.006, P < 0.000 1; the tissue chip: HR=1.926, 95%CI: 1.108~3.348, P=0.02). Cell adhesion molecules-related genes were was significantly enriched in the gastric cancer tissue with high expression of NPC2, suggesting it may be involved in the invasion and migration of gastric cancer cells. Down-regulation of NPC2 significantly reduced the migration ability of SGC7901 cells (NC vs si-1: P=0.000 04; NC vs si-2: P=0.000 449). Conclusion The expression of NPC2 is closely associated with the prognosis of gastric cancer and plays an important regulatory role in cell migration. NPC2 might serve as a potential biomarker for the diagnosis and treatment of gastric cancer.
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