Anoikis-related long non-coding RNA signatures to predict prognosis and small molecular drug response in cervical cancer

Background: Cervical cancer (CC) is a major health threat to females, and distal metastasis is common in patients with advanced CC. Anoikis is necessary for the development of distal metastases. Understanding the mechanisms associated with anoikis in CC is essential to improve its survival rate.Meth...

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Main Authors: Hao Liang, Lan Xiang, Huan Wu, Yang Liu, Wei Tian, Jianhua Zeng
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2023.1135626/full
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author Hao Liang
Lan Xiang
Huan Wu
Yang Liu
Wei Tian
Jianhua Zeng
author_facet Hao Liang
Lan Xiang
Huan Wu
Yang Liu
Wei Tian
Jianhua Zeng
author_sort Hao Liang
collection DOAJ
description Background: Cervical cancer (CC) is a major health threat to females, and distal metastasis is common in patients with advanced CC. Anoikis is necessary for the development of distal metastases. Understanding the mechanisms associated with anoikis in CC is essential to improve its survival rate.Methods: The expression matrix of long non-coding RNAs (lncRNAs) from cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients was extracted from The Cancer Genome Atlas (TCGA), and highly relevant anoikis-related lncRNAs (ARLs) were identified by the single sample gene set enrichment analysis (ssGSEA) method. ARLs-related molecular subtypes were discerned based on prognosis-related ARLs. ARLs-related prognostic risk score (APR_Score) was calculated and risk model was constructed using LASSO COX and COX models. In addition, we also assessed immune cell activity in the immune microenvironment (TME) for both subtypes and APR_Score groups. A nomogram was utilized for predicting improved clinical outcome. Finally, this study also discussed the potential of ARLs-related signatures in predicting response to immunotherapy and small molecular drugs.Results: Three ARLs-related subtypes were identified from TCGA-CESC (AC1, AC2, and AC3), with AC3 patients having the highest ARG scores, higher angiogenesis scores, and the worst prognosis. AC3 had lower immune cell scores in TME but higher immune checkpoint gene expression and higher potential for immune escape. Next, we constructed a prognostic risk model consisting of 7-ARLs. The APR_Score exhibited a greater robustness as an independent prognostic indicator in predicting prognosis, and the nomogram was a valuable tool for survival prediction. ARLs-related signatures emerged as a potential novel indicator for immunotherapy and small molecular drug selection.Conclusion: We firstly constructed novel ARLs-related signatures capable of predicting prognosis and offered novel ideas for therapy response in CC patients.
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spelling doaj.art-278b6a74960f4cd6bdf57601390fa9bb2023-03-20T04:56:35ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-03-011410.3389/fphar.2023.11356261135626Anoikis-related long non-coding RNA signatures to predict prognosis and small molecular drug response in cervical cancerHao Liang0Lan Xiang1Huan Wu2Yang Liu3Wei Tian4Jianhua Zeng5Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Tianjin, University of Traditional Chinese Medicine, Tianjin, ChinaDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaBackground: Cervical cancer (CC) is a major health threat to females, and distal metastasis is common in patients with advanced CC. Anoikis is necessary for the development of distal metastases. Understanding the mechanisms associated with anoikis in CC is essential to improve its survival rate.Methods: The expression matrix of long non-coding RNAs (lncRNAs) from cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients was extracted from The Cancer Genome Atlas (TCGA), and highly relevant anoikis-related lncRNAs (ARLs) were identified by the single sample gene set enrichment analysis (ssGSEA) method. ARLs-related molecular subtypes were discerned based on prognosis-related ARLs. ARLs-related prognostic risk score (APR_Score) was calculated and risk model was constructed using LASSO COX and COX models. In addition, we also assessed immune cell activity in the immune microenvironment (TME) for both subtypes and APR_Score groups. A nomogram was utilized for predicting improved clinical outcome. Finally, this study also discussed the potential of ARLs-related signatures in predicting response to immunotherapy and small molecular drugs.Results: Three ARLs-related subtypes were identified from TCGA-CESC (AC1, AC2, and AC3), with AC3 patients having the highest ARG scores, higher angiogenesis scores, and the worst prognosis. AC3 had lower immune cell scores in TME but higher immune checkpoint gene expression and higher potential for immune escape. Next, we constructed a prognostic risk model consisting of 7-ARLs. The APR_Score exhibited a greater robustness as an independent prognostic indicator in predicting prognosis, and the nomogram was a valuable tool for survival prediction. ARLs-related signatures emerged as a potential novel indicator for immunotherapy and small molecular drug selection.Conclusion: We firstly constructed novel ARLs-related signatures capable of predicting prognosis and offered novel ideas for therapy response in CC patients.https://www.frontiersin.org/articles/10.3389/fphar.2023.1135626/fullTCGAcervical canceranoikisLncRNAsprognosisimmunotherapy
spellingShingle Hao Liang
Lan Xiang
Huan Wu
Yang Liu
Wei Tian
Jianhua Zeng
Anoikis-related long non-coding RNA signatures to predict prognosis and small molecular drug response in cervical cancer
Frontiers in Pharmacology
TCGA
cervical cancer
anoikis
LncRNAs
prognosis
immunotherapy
title Anoikis-related long non-coding RNA signatures to predict prognosis and small molecular drug response in cervical cancer
title_full Anoikis-related long non-coding RNA signatures to predict prognosis and small molecular drug response in cervical cancer
title_fullStr Anoikis-related long non-coding RNA signatures to predict prognosis and small molecular drug response in cervical cancer
title_full_unstemmed Anoikis-related long non-coding RNA signatures to predict prognosis and small molecular drug response in cervical cancer
title_short Anoikis-related long non-coding RNA signatures to predict prognosis and small molecular drug response in cervical cancer
title_sort anoikis related long non coding rna signatures to predict prognosis and small molecular drug response in cervical cancer
topic TCGA
cervical cancer
anoikis
LncRNAs
prognosis
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fphar.2023.1135626/full
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