转录组测序揭示早期宫颈癌免疫活性和免疫沉默表型的特征

Q4 Medicine
O. Kurmyshkina, P. Kovchur, T. Volkova
{"title":"转录组测序揭示早期宫颈癌免疫活性和免疫沉默表型的特征","authors":"O. Kurmyshkina, P. Kovchur, T. Volkova","doi":"10.15789/1563-0625-coi-2800","DOIUrl":null,"url":null,"abstract":"Molecular classification, immuneheterogeneity, and the existence of distinct immunophenotypes of virus-associated cervical cancer (CeCa) remain as-yet weakly explored issues, and this is particularly true of its earliest clinical stages and pre-invasive forms: cervical intraepithelial neoplastic (CIN) lesions. The goal of the study was to identify transcriptomic landscapes of invasive CeCa at its initial progression that differ substantially in their immune-related characteristics, patterns of signaling pathways and composition of the microenvironment. Transcriptome profiling was carried out using RNA-sequencing on Illumina platform. A panel of surgical-derived tissue samples comprised human papillomavirus-positive CIN grade 1-3, cancer of FIGO IA1-IIB stages, and morphologically normal epithelium. Transcriptomic profiles were analyzed with the use of bioinformatics tools, such as gene set enrichment (GAGE) for signaling pathways, xCell enrichment for cell composition identification, and PREDA positional analysis of genomic data. Hierarchical clustering revealed heterogeneity of transcriptomic profiles within the early-stage CeCa, namely, the existence of two clusters of tumor samples and three functional patterns of genes showing coordinately altered expression. Pathway enrichment analysis on genes differently expressed between the two clusters/groups of CeCa samples (‘A' and ‘B') and CIN (group ‘C') suggested that invasive tumor progression in groups ‘A' and ‘B' might rely on immunologically dissimilar mechanisms. xCell analysis confirmed heterogeneity of changes in the abundancies of cell populations when comparing CeCa sample groups and CIN, along with differences in immune and stromal scores. PREDA demonstrated that these transcriptomic differences could be linked to different chromosomal regions and co-localized with particular gene families and potentially the reported virus integration hotspots. Overall, the existence and detectability of different transcriptomic immune-based phenotypes of invasive CeCa at its initial stages of progression is shown, which may provide new options to broaden the knowledge and applicability of target and immune anti-cancer therapy.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"34 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Characteristics of immune-active and immune-silent phenotypes of early-stage cervical carcinoma as revealed by transcriptome sequencing\",\"authors\":\"O. Kurmyshkina, P. Kovchur, T. Volkova\",\"doi\":\"10.15789/1563-0625-coi-2800\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Molecular classification, immuneheterogeneity, and the existence of distinct immunophenotypes of virus-associated cervical cancer (CeCa) remain as-yet weakly explored issues, and this is particularly true of its earliest clinical stages and pre-invasive forms: cervical intraepithelial neoplastic (CIN) lesions. The goal of the study was to identify transcriptomic landscapes of invasive CeCa at its initial progression that differ substantially in their immune-related characteristics, patterns of signaling pathways and composition of the microenvironment. Transcriptome profiling was carried out using RNA-sequencing on Illumina platform. A panel of surgical-derived tissue samples comprised human papillomavirus-positive CIN grade 1-3, cancer of FIGO IA1-IIB stages, and morphologically normal epithelium. Transcriptomic profiles were analyzed with the use of bioinformatics tools, such as gene set enrichment (GAGE) for signaling pathways, xCell enrichment for cell composition identification, and PREDA positional analysis of genomic data. Hierarchical clustering revealed heterogeneity of transcriptomic profiles within the early-stage CeCa, namely, the existence of two clusters of tumor samples and three functional patterns of genes showing coordinately altered expression. Pathway enrichment analysis on genes differently expressed between the two clusters/groups of CeCa samples (‘A' and ‘B') and CIN (group ‘C') suggested that invasive tumor progression in groups ‘A' and ‘B' might rely on immunologically dissimilar mechanisms. xCell analysis confirmed heterogeneity of changes in the abundancies of cell populations when comparing CeCa sample groups and CIN, along with differences in immune and stromal scores. PREDA demonstrated that these transcriptomic differences could be linked to different chromosomal regions and co-localized with particular gene families and potentially the reported virus integration hotspots. Overall, the existence and detectability of different transcriptomic immune-based phenotypes of invasive CeCa at its initial stages of progression is shown, which may provide new options to broaden the knowledge and applicability of target and immune anti-cancer therapy.\",\"PeriodicalId\":37835,\"journal\":{\"name\":\"Medical Immunology (Russia)\",\"volume\":\"34 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Medical Immunology (Russia)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.15789/1563-0625-coi-2800\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Immunology (Russia)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.15789/1563-0625-coi-2800","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

摘要

病毒相关性宫颈癌(CeCa)的分子分类、免疫异质性和不同免疫表型的存在仍然是尚未充分探讨的问题,特别是在其早期临床阶段和侵袭前形式:宫颈上皮内肿瘤(CIN)病变。该研究的目的是确定侵袭性CeCa在其初始进展阶段的转录组学景观,这些转录组学景观在其免疫相关特征、信号通路模式和微环境组成方面存在很大差异。在Illumina平台上使用rna测序进行转录组分析。一组手术来源的组织样本包括人乳头瘤病毒CIN 1-3级阳性、FIGO IA1-IIB期癌和形态正常的上皮。转录组学分析使用生物信息学工具,如基因集富集(GAGE)用于信号通路,xCell富集用于细胞组成鉴定,PREDA定位分析基因组数据。分层聚类揭示了早期CeCa中转录组谱的异质性,即存在两类肿瘤样本和三种协调改变表达的基因功能模式。两组CeCa样本(“A”和“B”)和CIN(“C”组)中不同表达基因的途径富集分析表明,“A”组和“B”组的浸润性肿瘤进展可能依赖于不同的免疫机制。xCell分析证实,在比较CeCa样本组和CIN时,细胞群丰度的变化具有异质性,以及免疫和基质评分的差异。PREDA表明,这些转录组差异可能与不同的染色体区域有关,并与特定的基因家族共定位,并可能与已报道的病毒整合热点共定位。综上所述,浸润性CeCa在其发展的初始阶段存在不同的转录组免疫表型并可检测,这可能为扩大靶向和免疫抗癌治疗的知识和适用性提供新的选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Characteristics of immune-active and immune-silent phenotypes of early-stage cervical carcinoma as revealed by transcriptome sequencing
Molecular classification, immuneheterogeneity, and the existence of distinct immunophenotypes of virus-associated cervical cancer (CeCa) remain as-yet weakly explored issues, and this is particularly true of its earliest clinical stages and pre-invasive forms: cervical intraepithelial neoplastic (CIN) lesions. The goal of the study was to identify transcriptomic landscapes of invasive CeCa at its initial progression that differ substantially in their immune-related characteristics, patterns of signaling pathways and composition of the microenvironment. Transcriptome profiling was carried out using RNA-sequencing on Illumina platform. A panel of surgical-derived tissue samples comprised human papillomavirus-positive CIN grade 1-3, cancer of FIGO IA1-IIB stages, and morphologically normal epithelium. Transcriptomic profiles were analyzed with the use of bioinformatics tools, such as gene set enrichment (GAGE) for signaling pathways, xCell enrichment for cell composition identification, and PREDA positional analysis of genomic data. Hierarchical clustering revealed heterogeneity of transcriptomic profiles within the early-stage CeCa, namely, the existence of two clusters of tumor samples and three functional patterns of genes showing coordinately altered expression. Pathway enrichment analysis on genes differently expressed between the two clusters/groups of CeCa samples (‘A' and ‘B') and CIN (group ‘C') suggested that invasive tumor progression in groups ‘A' and ‘B' might rely on immunologically dissimilar mechanisms. xCell analysis confirmed heterogeneity of changes in the abundancies of cell populations when comparing CeCa sample groups and CIN, along with differences in immune and stromal scores. PREDA demonstrated that these transcriptomic differences could be linked to different chromosomal regions and co-localized with particular gene families and potentially the reported virus integration hotspots. Overall, the existence and detectability of different transcriptomic immune-based phenotypes of invasive CeCa at its initial stages of progression is shown, which may provide new options to broaden the knowledge and applicability of target and immune anti-cancer therapy.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Medical Immunology (Russia)
Medical Immunology (Russia) Medicine-Immunology and Allergy
CiteScore
0.70
自引率
0.00%
发文量
88
审稿时长
12 weeks
期刊介绍: The journal mission is to promote scientific achievements in fundamental and applied immunology to various medical fields, the publication of reviews, lectures, essays by leading domestic and foreign experts in the field of fundamental and experimental immunology, clinical immunology, allergology, immunodiagnostics and immunotherapy of infectious, allergy, autoimmune diseases and cancer.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信