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Identification of a Four Hypoxia-Associated Long Non-Coding RNA Signature and Establishment of a Nomogram Predicting Prognosis of Clear Cell Renal Cell Carcinoma.

ABSTRACT: To identify novel hypoxia-associated long non-coding RNAs (lncRNAs) as potential biomarkers, we developed a risk stratification signature and constructed a prognosis prediction nomogram of clear cell renal cell carcinoma (ccRCC). Hypoxia-related lncRNAs were identified through Pearson correlation analysis between the expression profiles of hypoxia-related differentially expressed genes and lncRNAs from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset. Then, a signature of four key lncRNAs (COMETT, EMX2OS, AC026462.3, and HAGLR) was developed. The four lncRNAs were downregulated in high-grade, advanced stage, and high-risk ccRCC. The signature had an independent and long-standing prognosis prediction ability up to a 10-year follow-up. Notably, the risk score was significantly positively correlated with the infiltration abundances of six immune cells from the Tumor IMmune Estimation Resource (TIMER). The gene set enrichment analysis (GSEA) also suggested that the signature was involved in metabolism and tumorigenesis, which were closely related to the hypoxic tumor microenvironment. Ultimately, a nomogram of signature, age, stage, and grade, was built to predict the individual long-term survival possibility. Finally, the expressions of four lncRNAs were validated by quantitative real-time PCR (qRT-PCR). Our study identified a four-lncRNA signature and established a prognostic nomogram that reliably predicts survival in ccRCC. The findings may be beneficial to therapeutic customization and medical decision-making.

SUBMITTER: Chen H

PROVIDER: S-EPMC8353455 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeThe present study aims to comprehensively investigate the prognostic value of a radiomic nomogram that integrates contrast-enhanced computed tomography (CECT) radiomic signature and clinicopathological parameters in kidney renal clear cell carcinoma (KIRC).MethodsA total of 136 and 78 KIRC patients from the training and validation cohorts were included in the retrospective study. The intraclass correlation coefficient (ICC) was used to assess reproducibility of radiomic feature extraction. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) as well as multivariate Cox analysis were utilized to construct radiomic signature and clinical signature in the training cohort. A prognostic nomogram was established containing a radiomic signature and clinicopathological parameters by using a multivariate Cox analysis. The predictive ability of the nomogram [relative operating characteristic curve (ROC), concordance index (C-index), Hosmer-Lemeshow test, and calibration curve] was evaluated in the training cohort and validated in the validation cohort. Patients were split into high- and low-risk groups, and the Kaplan-Meier (KM) method was conducted to identify the forecasting ability of the established models. In addition, genes related with the radiomic risk score were determined by weighted correlation network analysis (WGCNA) and were used to conduct functional analysis.ResultsA total of 2,944 radiomic features were acquired from the tumor volumes of interest (VOIs) of CECT images. The radiomic signature, including ten selected features, and the clinical signature, including three selected clinical variables, showed good performance in the training and validation cohorts [area under the curve (AUC), 0.897 and 0.712 for the radiomic signature; 0.827 and 0.822 for the clinical signature, respectively]. The radiomic prognostic nomogram showed favorable performance and calibration in the training cohort (AUC, 0.896, C-index, 0.846), which was verified in the validation cohort (AUC, 0.768). KM curves indicated that the progression-free interval (PFI) time was dramatically shorter in the high-risk group than in the low-risk group. The functional analysis indicated that radiomic signature was significantly associated with T cell activation.ConclusionsThe nomogram combined with CECT radiomic and clinicopathological signatures exhibits excellent power in predicting the PFI of KIRC patients, which may aid in clinical management and prognostic evaluation of cancer patients.

Dataset Information

Identification of a Four Hypoxia-Associated Long Non-Coding RNA Signature and Establishment of a Nomogram Predicting Prognosis of Clear Cell Renal Cell Carcinoma.

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