The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress

Xuefeng Lv; Yanyan Jia; Jinpeng Li; Shu Deng; Enwu Yuan

doi:10.3389/fphar.2023.1234181

The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress

Front Pharmacol. 2023 Sep 21:14:1234181. doi: 10.3389/fphar.2023.1234181. eCollection 2023.

Authors

Xuefeng Lv^#¹, Yanyan Jia^#², Jinpeng Li¹, Shu Deng¹, Enwu Yuan¹

Affiliations

¹ Department of Laboratory Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
² Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

^# Contributed equally.

Abstract

Introduction: The immune-related lncRNAs (IRLs) are critical for the development of cervical cancer (CC), but it is still unclear how exactly ILRs contribute to CC. In this study, we aimed to examine the relationship between IRL and CC in detail. Methods: First, the RNAseq data and clinical data of CC patients were collected from The Cancer Genome Atlas (TCGA) database, along with the immune genes from the Import database. We used univariate cox and least absolute shrinkage and selection operator (lasso) to obtain IRLs for prediction after screening the variables. According to the expression levels and risk coefficients of IRLs, the riskscore were calculated. We analyzed the relationship between the model and oxidative stress. We stratified the risk model into two as the high and low-risk groups. We also evaluated the survival differences, immune cell differences, immunotherapeutic response differences, and drug sensitivity differences between the risk groups. Finally, the genes in the model were experimentally validated. Results: Based on the above analyses, we further selected four IRLs (TFAP2A.AS1, AP000911.1, AL133215.2, and LINC02078) to construct the risk model. The model was associated with oxidative-stress-related genes, especially SOD2 and OGG1. Patients in the high-risk group had a lower overall survival than those in the low-risk group. Riskscore was positively correlated with resting mast cells, neutrophils, and CD8+ T-cells. Patients in the low-risk group showed a greater sensitivity to immunosuppression therapy. In addition, we found that patients with the PIK3CA mutation were more sensitive to chemotherapeutic agents such as dasatinib, afatinib, dinaciclib and pelitinib. The function of AL133215.2 was verified, which was consistent with previous findings, and AL133215.2 exerted a pro-tumorigenic effect. We also found that AL133215.2 was closely associated with oxidative-stress-related pathways. Discussion: The results suggested that risk modeling might be useful for prognosticating patients with CC and opening up new routes for immunotherapy.

Keywords: cervical cancer; immune-related lncRNAs; immunotherapy; oxidative stress; prognosis.

Grants and funding

This study was funded by grants from the Scientific and Technological Project of Henan Province (172102310077). Funds for Creative Research Team of Henan Province.