A prognostic lncRNA signature associated with ribonucleotide reductase predicts overall survival and immune landscape in hepatocellular carcinoma
TL;DR
The RR‐related lncRNA signature integrates prognostic, immune, and metabolic features in HCC and may serve as a promising tool for risk stratification and personalized treatment guidance, while the identified lncRNAs provide potential candidates for further mechanistic investigation.
Abstract
Introduction Hepatocellular carcinoma (HCC) is a major cause of cancer‐related mortality, and effective prognostic stratification remains urgently needed. Ribonucleotide reductase (RR), consisting mainly of RRM1 and RRM2, plays a critical role in nucleotide metabolism and tumor progression. This study aimed to develop an RR‐related long non‐coding RNA (lncRNA) signature for predicting prognosis and exploring potential therapeutic implications in HCC. Methods Transcriptomic and clinical data from 377 HCC patients in The Cancer Genome Atlas (TCGA) database were analyzed. Molecular subgroups were identified based on RRM1 and RRM2 expression. Differentially expressed RR‐related lncRNAs were screened, and an RR‐indexed lncRNA prognostic signature (RILPS) was established using univariate Cox and LASSO Cox regression analyses. A nomogram integrating RILPS and M stage was constructed, followed by analyses of immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), pathway enrichment, and drug sensitivity. Results Two distinct RRM1/RRM2‐associated molecular clusters were identified. A 65‐lncRNA‐based RILPS model was developed and effectively stratified HCC patients into different prognostic groups. The RILPS‐M stage nomogram showed favorable predictive performance, with AUC values of 0.767, 0.800, and 0.820 for 1‐, 3‐, and 5‐year overall survival, respectively. The high‐RILPS group exhibited increased immune infiltration, higher TMB, and MSI characteristics, whereas the low‐RILPS group was enriched in metabolic pathways. Key lncRNAs, including NBAT1, LINC01138, and LINC00671, were associated with HCC prognosis and may contribute to tumor progression. Drug sensitivity analysis suggested potential therapeutic differences between RILPS‐defined subgroups. Discussion The RR‐related lncRNA signature integrates prognostic, immune, and metabolic features in HCC. RILPS may serve as a promising tool for risk stratification and personalized treatment guidance, while the identified lncRNAs provide potential candidates for further mechanistic investigation.