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

Hao Liang; Lan Xiang; Huan Wu; Yang Liu; Wei Tian; Jianhua Zeng

doi:10.3389/fphar.2023.1135626

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

Front Pharmacol. 2023 Mar 20:14:1135626. doi: 10.3389/fphar.2023.1135626. eCollection 2023.

Authors

Hao Liang¹, Lan Xiang², Huan Wu¹, Yang Liu¹, Wei Tian³, Jianhua Zeng¹

Affiliations

¹ Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
² Department of Hepatobiliary Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
³ Department of General Surgery, The Second Affiliated Hospital of Tianjin, University of Traditional Chinese Medicine, Tianjin, China.

Abstract

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.

Keywords: LncRNAs; TCGA; anoikis; cervical cancer; immunotherapy; prognosis; small molecular drug.

Grants and funding

The subject was funded by the General Program of Chongqing Natural Science Foundation: Study on the Role of CircRNA-0008193 Targeting miR-1226-5p in Regulating PD-L1 in Immune Escape of Cervical Cancer(cstc2021jcyj-msxmX0219). We are grateful for the support of the Tianjin Municipal Education Commission Scientific Research Program Project (2018KJ036).