升高的类解聚素金属蛋白酶-1（ADAMDEC1）表达与乳腺癌患者化疗敏感性增加及预后改善相关。

Elevated ADAM-like Decysin-1 (ADAMDEC1) expression is associated with increased chemo-sensitivity and improved prognosis in breast cancer patients.

作者信息

Chai Na, Xie Peilin, Chen Heyan, Li Yijun, Zhao Yuting, He Jianjun, Zhang Huimin

机构信息

Department of Breast Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

Ann Transl Med. 2023 Jan 15;11(1):14. doi: 10.21037/atm-22-6319.

DOI:10.21037/atm-22-6319

PMID:36760254

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9906202/

Abstract

BACKGROUND

Chemoresistance is problematic and its mechanisms are unclear in breast cancer. More predictive markers are urgently required.

METHODS

GSE32646, GSE34138, and GSE20271 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) between chemosensitive and chemoresistant tumors. LinkedOmics was used to analyze ADAM-like Decysin-1 (ADAMDEC1) expression among patients with different clinical characteristics and detect co-expression genes for functional analysis. Tumor Immune Estimation Resource (TIMER) and an integrated repository portal for tumor-immune system interactions (TISIDB) were used to investigate the association between the target gene and the immune response. Gene Set Cancer Analysis (GSCA) was utilized to explore the related pathways of ADAMDEC1 and evaluate the correlation between the expression of ADAMDEC1 and drug sensitivity. RNA22, miRWalk, and miRmap were used to predict the upstream micro ribonucleic acids (miRNAs) regulating ADAMDEC1 expression, while DIANA-LncBase v2 was applied to predict the upstream long non-coding ribonucleic acids (lncRNAs). Kaplan-Meier curve analysis was applied to determine the survival time.

RESULTS

We identified that ADAMDEC1 was upregulated among chemosensitive triple-negative breast cancer (TNBC) tissues in GSE32646, GSE34138, and GSE20271. Higher expression of ADAMDEC1 indicated longer survival in breast cancer. Next, we found that ADAMDEC1 was significantly related to the immune response in breast cancer through functional enrichment analysis and further meta-data validation. Moreover, we recognized that hsa-miR-4534 was the potential upstream miRNA regulating ADAMDEC1 expression and Taurine Up-Regulated 1 (TUG1) was the most likely upstream lncRNA of ADAMDEC1 and hsa-miR-4534. Finally, the correlation between ADAMDEC1 and chemosensitivity was confirmed through drug database analysis.

CONCLUSIONS

Elevated ADAMDEC1 expression is associated with increased chemosensitivity and better prognosis in breast cancer patients.

摘要

背景

化疗耐药是个问题，且其机制在乳腺癌中尚不清楚。迫切需要更多的预测标志物。

方法

从基因表达综合数据库（GEO）下载GSE32646、GSE34138和GSE20271，以鉴定化疗敏感和化疗耐药肿瘤之间的差异表达基因（DEG）。利用LinkedOmics分析不同临床特征患者中类解整合素金属蛋白酶1（ADAMDEC1）的表达，并检测共表达基因以进行功能分析。使用肿瘤免疫估计资源（TIMER）和肿瘤 - 免疫系统相互作用综合知识库门户（TISIDB）来研究靶基因与免疫反应之间的关联。利用基因集癌症分析（GSCA）探索ADAMDEC1的相关途径，并评估ADAMDEC1表达与药物敏感性之间的相关性。使用RNA22、miRWalk和miRmap预测调节ADAMDEC1表达的上游微小核糖核酸（miRNA），而应用DIANA-LncBase v2预测上游长链非编码核糖核酸（lncRNA）。应用Kaplan-Meier曲线分析来确定生存时间。

结果

我们发现在GSE32646、GSE34138和GSE20271中，化疗敏感的三阴性乳腺癌（TNBC）组织中ADAMDEC1表达上调。ADAMDEC1表达较高表明乳腺癌患者生存期较长。接下来，通过功能富集分析和进一步的元数据验证，我们发现ADAMDEC1与乳腺癌的免疫反应显著相关。此外，我们认识到hsa-miR-4534是调节ADAMDEC1表达的潜在上游miRNA，而牛磺酸上调基因1（TUG1）是ADAMDEC1和hsa-miR-4534最可能的上游lncRNA。最后，通过药物数据库分析证实了ADAMDEC1与化疗敏感性之间的相关性。