DNA损伤应答下干性的翻译后调控参与了龈颊口腔鳞状细胞癌的复发和进展

Sachendra Kumar , Annapoorni Rangarajan , Debnath Pal
{"title":"DNA损伤应答下干性的翻译后调控参与了龈颊口腔鳞状细胞癌的复发和进展","authors":"Sachendra Kumar ,&nbsp;Annapoorni Rangarajan ,&nbsp;Debnath Pal","doi":"10.1016/j.oor.2025.100730","DOIUrl":null,"url":null,"abstract":"<div><div>Tobacco consumption (smoking and specifically smokeless form) in India contributes to a high prevalence of gingivobuccal oral squamous cell carcinoma (OSCC-GB). OSCC-GB exhibits high rates of locoregional relapse and therapeutic resistance, often attributed to the involvement of cancer stem cells (CSCs). The goal of this study is to leverage the generalizability of the machine learning prediction model for ‘Tumor Status’ for a comparative somatic mutation analysis between ‘With Tumor’ (recurred/relapsed/progressed) and ‘Tumor Free’ (disease-free/complete remission) OSCC-GB patients. Our results showed that support vector machines (SVM) classified the ‘Tumor Status’ classes at a mean accuracy of 89% based on clinical features. Furthermore, RNA-seq based somatic mutation analysis using the classified groups revealed molecular mechanisms underlying tumor progression and remission within OSCC-GB subgroups. The identified mutational signature (C&gt;T mutations) related to DNA damage indicates the influence of tobacco-related carcinogens in OSCC-GB subgroups. The analysis of distinct somatic variants, functional impact predictions, protein-protein interactions, and survival analysis highlights the involvement of DNA damage response (DDR)-related genes in ‘With Tumor’, with particular focus on the significant role of the Mitogen-activated protein kinase associated protein 1 (MAPKAP1) gene, a key player in the mTORC2 signaling pathway. The study indicates that loss-of-function in the identified MAPKAP1 somatic variant may promote stemness and elevated risk of relapse and disease progression in OSCC-GB under conditions of DDR in ‘With Tumor’ OSCC-GB, potentially contributing to increased mortality rates among Indian OSCC-GB patients.</div></div>","PeriodicalId":94378,"journal":{"name":"Oral Oncology Reports","volume":"13 ","pages":"Article 100730"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Post-translational regulation of stemness under DNA damage response contributes to the gingivobuccal oral squamous cell carcinoma relapse and progression\",\"authors\":\"Sachendra Kumar ,&nbsp;Annapoorni Rangarajan ,&nbsp;Debnath Pal\",\"doi\":\"10.1016/j.oor.2025.100730\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Tobacco consumption (smoking and specifically smokeless form) in India contributes to a high prevalence of gingivobuccal oral squamous cell carcinoma (OSCC-GB). OSCC-GB exhibits high rates of locoregional relapse and therapeutic resistance, often attributed to the involvement of cancer stem cells (CSCs). The goal of this study is to leverage the generalizability of the machine learning prediction model for ‘Tumor Status’ for a comparative somatic mutation analysis between ‘With Tumor’ (recurred/relapsed/progressed) and ‘Tumor Free’ (disease-free/complete remission) OSCC-GB patients. Our results showed that support vector machines (SVM) classified the ‘Tumor Status’ classes at a mean accuracy of 89% based on clinical features. Furthermore, RNA-seq based somatic mutation analysis using the classified groups revealed molecular mechanisms underlying tumor progression and remission within OSCC-GB subgroups. The identified mutational signature (C&gt;T mutations) related to DNA damage indicates the influence of tobacco-related carcinogens in OSCC-GB subgroups. The analysis of distinct somatic variants, functional impact predictions, protein-protein interactions, and survival analysis highlights the involvement of DNA damage response (DDR)-related genes in ‘With Tumor’, with particular focus on the significant role of the Mitogen-activated protein kinase associated protein 1 (MAPKAP1) gene, a key player in the mTORC2 signaling pathway. The study indicates that loss-of-function in the identified MAPKAP1 somatic variant may promote stemness and elevated risk of relapse and disease progression in OSCC-GB under conditions of DDR in ‘With Tumor’ OSCC-GB, potentially contributing to increased mortality rates among Indian OSCC-GB patients.</div></div>\",\"PeriodicalId\":94378,\"journal\":{\"name\":\"Oral Oncology Reports\",\"volume\":\"13 \",\"pages\":\"Article 100730\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-02-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oral Oncology Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2772906025000184\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oral Oncology Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2772906025000184","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

印度的烟草消费(吸烟,特别是无烟形式)导致牙龈-口腔鳞状细胞癌(OSCC-GB)的高患病率。OSCC-GB表现出高的局部复发率和治疗耐药性,通常归因于癌症干细胞(CSCs)的参与。本研究的目的是利用“肿瘤状态”机器学习预测模型的通用性,对“有肿瘤”(复发/复发/进展)和“无肿瘤”(无病/完全缓解)OSCC-GB患者进行比较体细胞突变分析。我们的研究结果表明,支持向量机(SVM)基于临床特征对“肿瘤状态”分类的平均准确率为89%。此外,使用分类组进行基于RNA-seq的体细胞突变分析,揭示了OSCC-GB亚组中肿瘤进展和缓解的分子机制。鉴定出的与DNA损伤相关的突变特征(C>;T突变)表明烟草相关致癌物对OSCC-GB亚组的影响。对不同体细胞变异、功能影响预测、蛋白-蛋白相互作用和生存分析的分析强调了DNA损伤反应(DDR)相关基因在“With Tumor”中的参与,特别关注了丝裂原活化蛋白激酶相关蛋白1 (MAPKAP1)基因的重要作用,该基因是mTORC2信号通路的关键参与者。该研究表明,在“伴有肿瘤”的OSCC-GB中,在DDR条件下,鉴定的MAPKAP1体细胞变异的功能丧失可能促进OSCC-GB的干性、复发和疾病进展的风险升高,可能导致印度OSCC-GB患者死亡率增加。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Post-translational regulation of stemness under DNA damage response contributes to the gingivobuccal oral squamous cell carcinoma relapse and progression
Tobacco consumption (smoking and specifically smokeless form) in India contributes to a high prevalence of gingivobuccal oral squamous cell carcinoma (OSCC-GB). OSCC-GB exhibits high rates of locoregional relapse and therapeutic resistance, often attributed to the involvement of cancer stem cells (CSCs). The goal of this study is to leverage the generalizability of the machine learning prediction model for ‘Tumor Status’ for a comparative somatic mutation analysis between ‘With Tumor’ (recurred/relapsed/progressed) and ‘Tumor Free’ (disease-free/complete remission) OSCC-GB patients. Our results showed that support vector machines (SVM) classified the ‘Tumor Status’ classes at a mean accuracy of 89% based on clinical features. Furthermore, RNA-seq based somatic mutation analysis using the classified groups revealed molecular mechanisms underlying tumor progression and remission within OSCC-GB subgroups. The identified mutational signature (C>T mutations) related to DNA damage indicates the influence of tobacco-related carcinogens in OSCC-GB subgroups. The analysis of distinct somatic variants, functional impact predictions, protein-protein interactions, and survival analysis highlights the involvement of DNA damage response (DDR)-related genes in ‘With Tumor’, with particular focus on the significant role of the Mitogen-activated protein kinase associated protein 1 (MAPKAP1) gene, a key player in the mTORC2 signaling pathway. The study indicates that loss-of-function in the identified MAPKAP1 somatic variant may promote stemness and elevated risk of relapse and disease progression in OSCC-GB under conditions of DDR in ‘With Tumor’ OSCC-GB, potentially contributing to increased mortality rates among Indian OSCC-GB patients.
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
CiteScore
0.20
自引率
0.00%
发文量
0
×
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