人激肽释放酶5（KLK5）在化生三阴性乳腺癌症中表达的生物信息学分析

Cancer Innovation Pub Date : 2023-10-15 DOI:10.1002/cai2.96

Yue Song, Guiying Bai, Xiaoqing Li, Liyan Zhou, Yiran Si, Xiaohui Liu, Yilin Deng, Yehui Shi

{"title":"人激肽释放酶5（KLK5）在化生三阴性乳腺癌症中表达的生物信息学分析","authors":"Yue Song, Guiying Bai, Xiaoqing Li, Liyan Zhou, Yiran Si, Xiaohui Liu, Yilin Deng, Yehui Shi","doi":"10.1002/cai2.96","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype; most cases are triple-negative breast cancers (TNBCs) and are poorly responsive to conventional systemic therapy. Few potential diagnostic and prognostic markers for distinguishing between metaplastic TNBC and nonmetaplastic TNBC have been discovered. We performed bioinformatic analysis to explore the underlying mechanism by which metaplastic TNBC differs from nonmetaplastic TNBC and provides potential pathogenic genes of metaplastic TNBC.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Differentially expressed genes (DEGs) in metaplastic tumors and nonmetaplastic tumors from TNBC patients were screened using GSE165407. The GSE76275 data set and The Cancer Genome Atlas (TCGA) database were used to screen DEGs in TNBC and non-TNBC. Metascape and DAVID were used for the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) analysis of DEGs. Online databases, including UALCAN, GEPIA, HPA, Breast Cancer Gene-Expression Miner, and quantitative PCR and western blot, were used to examine <i>KLK5</i> messenger RNA and protein expression in breast cancer. Analysis of <i>KLK5</i>‑associated genes was performed with TCGA data, and the LinkedOmics database was used to detect the genes co-expressed with <i>KLK5</i>. STRING (Search Tool for the Retrieval of Interacting Genes) and Cytoscape were used to screen for hub genes. Kaplan‑Meier plotter was used for survival analysis.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p><i>KLK5</i> was identified among the DEGs in nonmetaplastic TNBC and metaplastic TNBC. The <i>KLK5</i> gene was overexpressed in nonmetaplastic TNBC but downregulated in metaplastic TNBC. KEGG and GO analyses revealed that epithelial-to-mesenchymal transition was a pathogenic mechanism in metaplastic TNBC and an important pathway by which <i>KLK5</i> and its associated genes <i>DSG1</i> and <i>DSG3</i> influence metaplastic TNBC progression. Prognosis analysis showed that only low expression of <i>KLK5</i> in metaplastic TNBC had clinical significance.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our research indicated that <i>KLK5</i> may be a pivotal molecule with a key role in the mechanism of tumorigenesis in metaplastic TNBC.</p>\n </section>\n </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"2 5","pages":"376-390"},"PeriodicalIF":0.0000,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Bioinformatics analysis of human kallikrein 5 (KLK5) expression in metaplastic triple-negative breast cancer\",\"authors\":\"Yue Song, Guiying Bai, Xiaoqing Li, Liyan Zhou, Yiran Si, Xiaohui Liu, Yilin Deng, Yehui Shi\",\"doi\":\"10.1002/cai2.96\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype; most cases are triple-negative breast cancers (TNBCs) and are poorly responsive to conventional systemic therapy. Few potential diagnostic and prognostic markers for distinguishing between metaplastic TNBC and nonmetaplastic TNBC have been discovered. We performed bioinformatic analysis to explore the underlying mechanism by which metaplastic TNBC differs from nonmetaplastic TNBC and provides potential pathogenic genes of metaplastic TNBC.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Differentially expressed genes (DEGs) in metaplastic tumors and nonmetaplastic tumors from TNBC patients were screened using GSE165407. The GSE76275 data set and The Cancer Genome Atlas (TCGA) database were used to screen DEGs in TNBC and non-TNBC. Metascape and DAVID were used for the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) analysis of DEGs. Online databases, including UALCAN, GEPIA, HPA, Breast Cancer Gene-Expression Miner, and quantitative PCR and western blot, were used to examine <i>KLK5</i> messenger RNA and protein expression in breast cancer. Analysis of <i>KLK5</i>‑associated genes was performed with TCGA data, and the LinkedOmics database was used to detect the genes co-expressed with <i>KLK5</i>. STRING (Search Tool for the Retrieval of Interacting Genes) and Cytoscape were used to screen for hub genes. Kaplan‑Meier plotter was used for survival analysis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p><i>KLK5</i> was identified among the DEGs in nonmetaplastic TNBC and metaplastic TNBC. The <i>KLK5</i> gene was overexpressed in nonmetaplastic TNBC but downregulated in metaplastic TNBC. KEGG and GO analyses revealed that epithelial-to-mesenchymal transition was a pathogenic mechanism in metaplastic TNBC and an important pathway by which <i>KLK5</i> and its associated genes <i>DSG1</i> and <i>DSG3</i> influence metaplastic TNBC progression. Prognosis analysis showed that only low expression of <i>KLK5</i> in metaplastic TNBC had clinical significance.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Our research indicated that <i>KLK5</i> may be a pivotal molecule with a key role in the mechanism of tumorigenesis in metaplastic TNBC.</p>\\n </section>\\n </div>\",\"PeriodicalId\":100212,\"journal\":{\"name\":\"Cancer Innovation\",\"volume\":\"2 5\",\"pages\":\"376-390\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-10-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Innovation\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cai2.96\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Innovation","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cai2.96","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

摘要

背景Metaplastic乳腺癌（MBC）是一种罕见的癌症亚型；大多数病例是三阴性乳腺癌（TNBCs），对传统的全身治疗反应不佳。很少有潜在的诊断和预后标志物可以区分化生TNBC和非化生TNBC。我们进行了生物信息学分析，以探索化生TNBC与非化生TNBC不同的潜在机制，并提供了化生TN不列颠哥伦比亚省的潜在致病基因。方法应用GSE165407筛选TNBC患者化生肿瘤和非化生肿瘤的差异表达基因。GSE76275数据集和癌症基因组图谱（TCGA）数据库用于筛选TNBC和非TNBC中的DEG。Metascape和DAVID用于京都基因和基因组百科全书（KEGG）的DEG富集分析和基因本体论（GO）分析。在线数据库，包括UALCAN、GEPIA、HPA、乳腺癌症基因表达Miner，以及定量PCR和蛋白质印迹，用于检测KLK5信使RNA和蛋白质在癌症中的表达。利用TCGA数据对KLK5相关基因进行分析，并使用LinkedOmics数据库检测与KLK5共表达的基因。STRING（检索相互作用基因的搜索工具）和Cytoscape用于筛选枢纽基因。Kaplan‑Meier绘图仪用于生存分析。结果KLK5在非转化性TNBC和化生性TNBC的DEG中均有表达。KLK5基因在非转化性TNBC中过表达，但在化生TNBC中下调。KEGG和GO分析表明，上皮-间质转化是化生TNBC的致病机制，也是KLK5及其相关基因DSG1和DSG3影响化生TNBC进展的重要途径。预后分析显示，只有KLK5在化生TNBC中的低表达才具有临床意义。结论KLK5可能是化生TNBC肿瘤发生机制中的关键分子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

摘要图片

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

Bioinformatics analysis of human kallikrein 5 (KLK5) expression in metaplastic triple-negative breast cancer

Background

Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype; most cases are triple-negative breast cancers (TNBCs) and are poorly responsive to conventional systemic therapy. Few potential diagnostic and prognostic markers for distinguishing between metaplastic TNBC and nonmetaplastic TNBC have been discovered. We performed bioinformatic analysis to explore the underlying mechanism by which metaplastic TNBC differs from nonmetaplastic TNBC and provides potential pathogenic genes of metaplastic TNBC.

Methods

Differentially expressed genes (DEGs) in metaplastic tumors and nonmetaplastic tumors from TNBC patients were screened using GSE165407. The GSE76275 data set and The Cancer Genome Atlas (TCGA) database were used to screen DEGs in TNBC and non-TNBC. Metascape and DAVID were used for the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) analysis of DEGs. Online databases, including UALCAN, GEPIA, HPA, Breast Cancer Gene-Expression Miner, and quantitative PCR and western blot, were used to examine KLK5 messenger RNA and protein expression in breast cancer. Analysis of KLK5‑associated genes was performed with TCGA data, and the LinkedOmics database was used to detect the genes co-expressed with KLK5. STRING (Search Tool for the Retrieval of Interacting Genes) and Cytoscape were used to screen for hub genes. Kaplan‑Meier plotter was used for survival analysis.

Results

KLK5 was identified among the DEGs in nonmetaplastic TNBC and metaplastic TNBC. The KLK5 gene was overexpressed in nonmetaplastic TNBC but downregulated in metaplastic TNBC. KEGG and GO analyses revealed that epithelial-to-mesenchymal transition was a pathogenic mechanism in metaplastic TNBC and an important pathway by which KLK5 and its associated genes DSG1 and DSG3 influence metaplastic TNBC progression. Prognosis analysis showed that only low expression of KLK5 in metaplastic TNBC had clinical significance.