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Background <p>Cuproptosis, a novel form of cell death, induces protein-toxic stress before leading to cell demise. However, studies exploring long noncoding RNA (LncRNA) related to cuproptosis in Rectum adenocarcinoma (READ) are limited. This study aims to identify prognostic markers associated with cuproptosis-related LncRNAs and their relationship with the immune microenvironment in READ using bioinformatics approaches.</p> Methods <p>RNA sequencing, genetic mutations, copy number variations, and clinical data for TCGA_READ were obtained from The Cancer Genome Atlas (TCGA). READ patients were randomly assigned to either a training cohort or a validation cohort. In the training cohort, the prognostic model was developed using least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression models. The prognostic significance of the model was further validated in both the validation and full cohorts. Tumor mutation burden (TMB), immune-related activities, and functional enrichment analyses (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG]) were performed to explore the relationship between LncRNAs and cuproptosis.</p> Results <p>From existing literature, we identified 22 genes associated with cuproptosis. Using co-expression analysis, we identified 421 LncRNAs related to cuproptosis. Cox regression analysis led to the identification of four cuproptosis-related LncRNAs (GPRACR, LINC01555, NIHCOLE, and MPC1-DT) as prognostic markers. Patients were stratified into high- and low-risk groups based on the median risk score. Kaplan–Meier survival analysis showed that patients in the high-risk group had significantly worse overall survival (OS) and progression-free survival (PFS), with higher mortality rates. Univariate and multivariate Cox regression analyses confirmed that the risk score was an independent prognostic factor. A nomogram was constructed using multivariate Cox regression to predict the survival outcomes of READ patients. The TMB in the low-risk group was significantly higher than in the high-risk group, and patients with low-risk scores and high TMB had the best OS. Using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm, we observed significant differences in immune markers, including TAM_M2, IFNG, and CD8, between the high- and low-risk groups.</p> Conclusion <p>In conclusion, the four cuproptosis-related LncRNAs identified in this study serve as reliable prognostic markers for READ patients. These findings provide novel insights into potential immunotherapeutic strategies and clinical applications in the management of READ.</p>

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A novel LncRNA signature associated with cuproptosis for prognostic prediction and immune response assessment in rectum adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月24日

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  • Minghe Lv,
  • Ruping Zhao

摘要

Background

Cuproptosis, a novel form of cell death, induces protein-toxic stress before leading to cell demise. However, studies exploring long noncoding RNA (LncRNA) related to cuproptosis in Rectum adenocarcinoma (READ) are limited. This study aims to identify prognostic markers associated with cuproptosis-related LncRNAs and their relationship with the immune microenvironment in READ using bioinformatics approaches.

Methods

RNA sequencing, genetic mutations, copy number variations, and clinical data for TCGA_READ were obtained from The Cancer Genome Atlas (TCGA). READ patients were randomly assigned to either a training cohort or a validation cohort. In the training cohort, the prognostic model was developed using least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression models. The prognostic significance of the model was further validated in both the validation and full cohorts. Tumor mutation burden (TMB), immune-related activities, and functional enrichment analyses (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG]) were performed to explore the relationship between LncRNAs and cuproptosis.

Results

From existing literature, we identified 22 genes associated with cuproptosis. Using co-expression analysis, we identified 421 LncRNAs related to cuproptosis. Cox regression analysis led to the identification of four cuproptosis-related LncRNAs (GPRACR, LINC01555, NIHCOLE, and MPC1-DT) as prognostic markers. Patients were stratified into high- and low-risk groups based on the median risk score. Kaplan–Meier survival analysis showed that patients in the high-risk group had significantly worse overall survival (OS) and progression-free survival (PFS), with higher mortality rates. Univariate and multivariate Cox regression analyses confirmed that the risk score was an independent prognostic factor. A nomogram was constructed using multivariate Cox regression to predict the survival outcomes of READ patients. The TMB in the low-risk group was significantly higher than in the high-risk group, and patients with low-risk scores and high TMB had the best OS. Using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm, we observed significant differences in immune markers, including TAM_M2, IFNG, and CD8, between the high- and low-risk groups.

Conclusion

In conclusion, the four cuproptosis-related LncRNAs identified in this study serve as reliable prognostic markers for READ patients. These findings provide novel insights into potential immunotherapeutic strategies and clinical applications in the management of READ.