GEMIN4, a potential therapeutic targets for patients with basal-like subtype breast cancer

Abstract

Abstract Background Basal-like breast cancer (BLBC) takes up about 10–20% of all breast cancer(BC), what’s more, BLBC has the lowest survival rate among all BC subtypes because of lacks of efficient treatment methods. We aimed to explore the molecules that can be used as diagnostic maker for BLBC at early stage and provide optimized treatment strategies for BLBC patients in this study. Methods Apply weighted gene co-expression network analysis (WGCNA) to identify gene modules related to BLBC;The functional enrichment of candidate genes related to BLBC in the red module of Go data package and KEGG analysis;Overlapping cross analysis of URGs and WGCNA to identify candidate genes in each BC subtype;Divide BCBL patients into high-risk and low-risk groups, and analyze the two groups of overall survival (OS) and relapse free survival (RFS);Screening of GEMIN4 dependent cell lines; QRT PCR was used to verify the expression of GEMIN4 transfected with siRNA; CCK8 was used to determine the effect of GEMIN4 on cell viability; Positive cell count detected by BrdU staining;GO and KEGG enrichment analysis of GEMIN4. Results The "red module" has the highest correlation with BLBC, with 913 promising candidate genes identified from the red module;913 red module candidate genes related to BLBC participated in multiple GO terms, and KEGG enrichment analysis results mainly enriched in estrogen signaling pathways and pathways in cancer;There are 386 overlapping candidate genes among the 913 "red module" genes identified by 1893 common URG and WGCNA;In BLBC patients, 9 highly expressed genes are associated with OS. Five highly expressed genes are associated with RFS. Kaplan Meier survival analysis suggests that high GEMIN4 expression levels are associated with poor prognosis in BLBC patients;The GEMIN4 gene dependency score in HCC1143 and CAL120 cell lines is negative and low; Si-GEMIN4-1 can significantly reduce the mRNA expression of GEMIN4; Si-GEMIN4 can inhibit cell viability; Si-GEMIN4 can reduce the number of positive cells;GO enrichment analysis showed that GEMIN4 is associated with DNA metabolism processes and adenylate binding; KEGG pathway enrichment analysis shows that GEMIN4 is related to ribosome biogenesis in eukaryotes. Conclusion We hypothesized that GEMIN4 may be the potential target for the treatment of BLBC.

Keywords

• Basal-like breast cancer
• GEMIN4
• Weighted gene co-expression network analysis
• Prognosis