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

Frontiers in Pharmacology

Pharmacology

Yanyan Jia¹  Enwu Yuan²  Shu Deng²  Jinpeng Li²  Xuefeng Lv² 

[1] Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China;Department of Laboratory Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China;

关键词: cervical cancer;    immune-related lncRNAs;    prognosis;    immunotherapy;    oxidative stress;   

DOI  :  10.3389/fphar.2023.1234181

 received in 2023-06-03, accepted in 2023-09-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Lv, Jia, Li, Deng and Yuan.