GEMIN4，基底样亚型乳腺癌患者的潜在治疗靶点。

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

机构信息

Department of Emergency Surgery, The Second Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, Qiqihar, People's Republic of China.

Department of International Education School, Qiqihar Medical University, Heilongjiang Province, Qiqihar, People's Republic of China.

出版信息

BMC Womens Health. 2023 Jul 28;23(1):396. doi: 10.1186/s12905-023-02547-1.

DOI:10.1186/s12905-023-02547-1

PMID:37507701

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10386636/

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.

摘要

背景

基底样乳腺癌（BLBC）约占所有乳腺癌（BC）的 10-20%，由于缺乏有效的治疗方法，BLBC 是所有 BC 亚型中生存率最低的。本研究旨在探索可作为早期 BLBC 诊断标志物的分子，并为 BLBC 患者提供优化的治疗策略。

方法

应用加权基因共表达网络分析（WGCNA）鉴定与 BLBC 相关的基因模块；对红色模块中与 BLBC 相关的候选基因进行 GO 数据包和 KEGG 分析的功能富集；对每个 BC 亚型的 URGs 和 WGCNA 的重叠交叉分析鉴定候选基因；将 BCBL 患者分为高危和低危组，分析两组的总生存期（OS）和无复发生存期（RFS）；筛选 GEMIN4 依赖性细胞系；使用 siRNA 转染 GEMIN4 后进行 QRT-PCR 验证；使用 CCK8 测定 GEMIN4 对细胞活力的影响；BrdU 染色检测阳性细胞计数；GEMIN4 的 GO 和 KEGG 富集分析。

结果

“红色模块”与 BLBC 相关性最高，从红色模块中鉴定出 913 个有前途的候选基因；与 BLBC 相关的 913 个红色模块候选基因参与了多个 GO 术语，KEGG 富集分析结果主要富集在雌激素信号通路和癌症途径中；在 1893 个共同 URGs 和 WGCNA 鉴定的 913 个“红色模块”基因中，有 386 个重叠候选基因；在 BLBC 患者中，9 个高表达基因与 OS 相关。有 5 个高表达基因与 RFS 相关。Kaplan-Meier 生存分析表明，GEMIN4 高表达与 BLBC 患者预后不良相关；HCC1143 和 CAL120 细胞系的 GEMIN4 基因依赖性评分呈负低；Si-GEMIN4-1 可显著降低 GEMIN4 的 mRNA 表达；Si-GEMIN4 可抑制细胞活力；Si-GEMIN4 可减少阳性细胞数；GO 富集分析表明，GEMIN4 与 DNA 代谢过程和腺嘌呤结合有关；KEGG 途径富集分析表明，GEMIN4 与真核生物核糖体生物发生有关。