TRANSCRIPTOME ANALYSIS REVEALED THE MOLECULAR SIGNATURES OF CISPLATIN-FLUOROURACIL COMBINED CHEMOTHERAPY RESISTANCE IN GASTRIC CANCER.

ABSTRACT

Gastric cancer (GC) is among the top five malignant tumors worldwide in terms of morbidity and death. Chemotherapy is the primary treatment for unresectable or advanced postoperative GC. Chemotherapy resistance developed against cisplatin-fluorouracil (CF) combined chemotherapy is one of the most common clinical issues in patients with GC, leading to poor prognosis. Two different methods were used to analyze GSE14210, and two gene sets were obtained. The first method involved performing the traditional difference analysis (adjusted p<0.05, |log2FC|>=1) by Network Analyst to obtain gene set 1, followed by conducting gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis on the obtained gene set. The second method involved using iDEP to make the weighted gene co-expression network analysis (WGCNA) and performing GO and KEGG enrichment analysis, to obtain gene set 2. Thereafter, the STRING database and Cytoscape were used to construct Protein-Protein Interaction (PPI) networks, screen core clusters, and hub genes of the two gene sets. Furthermore, the hub genes were verified in GSE14210 by the survival analysis method of the Kaplan-Meier plotter database. Finally, we analyzed the mRNA expression of the hub genes by UALCAN and the protein expression of the same by Human Protein Atlas (HPA). Three real hub genes with the same mRNA expression as that of protein were identified, including CENPB, MTA1, and GCNT3. Finally, we performed single gene GO and KEGG enrichment analyses to explore the possible mechanisms of action of these three genes. The mRNA and protein expressions of CENPB, MTA1, and GCNT3 were upregulated in CF-resistant GC patients, and they were significantly associated with bad overall survival (OS). CENPB, MTA1 and GCNT3 are expected to be biomarkers with promising clinical applications as potential therapeutic targets for patients with refractory GC treated with CF combined chemotherapy.