A Novel Necroptosis-related Long Non-coding RNA Signature Predicts Prognosis and Immune Response in Cervical Cancer Patients

Background: Necroptosis has been linked to the development of tumors. Long non-coding RNAs (IncRNAs) have been identified as having a major role in numerous biological and pathological procedures. Despite this, the precise role that necroptosis-related lncRNAs (NRLs) have in cervical cancer (CC) and their potential for predicting its prognosis is still to a large extent unclear.

Methods: Gene expression RNA-sequencing data, mutational data, and clinical profiles for 309 CC patients were obtained from the Cancer Genome Atlas (TCGA) database. The NRLs were then identified with Pearson correlation analysis followed by splitting of the patients into training and validation sets in a 3:2 ratio. Cox and LASSO regression models were performed to construct a cervical cancer prognostic signature based on NRLs. This 5-NRLs signature was then verified by Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curve, and nomogram for prognostic prediction. Further, a correlation study between the risk score (RS) and immune cell infiltration, immune checkpoint molecules, tumor mutation burden (TMB), and the sensitivity of chemotherapy drug was conducted. To validate the 5-NRLs, a quantitative reverse transcription polymerase chain reaction (qRT-PCR) was finally performed.

Results: The 5-NRLs signature was designed to accurately predict the prognosis of CC. It consists of AC092153.1, AC007686.3, LINC01281, AC009097.2, and RUSC1-AS1 and was found to be highly predictive using ROC and Kaplan-Meier curves. Furthermore, when analyzed through stratified survival analysis, it was confirmed to be an independent risk factor for prognosis. The nomogram and calibration curves further validated its clinical utility. Moreover, distinct differences between two risk groups were observed when examining immune cell infiltration, immune checkpoint molecules, somatic gene alterations and half-inhibitory concentration of anticancer drug.

Conclusions: The 5-NRLs signature is a novel and valuable tool for evaluating the prognosis of CC patients, providing clinicians with an informed decision-making framework to formulate tailored treatment plans for their patients.