Dataset Information

Development of an Autophagy-Related Gene Prognostic Model and Nomogram for Estimating Renal Clear Cell Carcinoma Survival.

ABSTRACT:

Background

Kidney renal clear cell carcinoma (KIRC) is a fatal malignancy of the urinary system. Autophagy is implicated in KIRC occurrence and development. Here, we evaluated the prognostic value of autophagy-related genes (ARGs) in kidney renal clear cell carcinoma.

Materials and methods

We analyzed RNA sequencing and clinical KIRC patient data obtained from TCGA and ICGC to develop an ARG prognostic signature. Differentially expressed ARGs were further evaluated by functional assessment and bioinformatic analysis. Next, ARG score was determined in 215 KIRC patients using univariable Cox and LASSO regression analyses. An ARG nomogram was built based on multivariable Cox analysis. The prognosis nomogram model based on the ARG signatures and clinicopathological information was evaluated for discrimination, calibration, and clinical usefulness.

Results

A total of 47 differentially expressed ARGs were identified. Of these, 8 candidates that significantly correlated with KIRC overall survival were subjected to LASSO analysis and an ARG score built. Functional enrichment and bioinformatic analysis were used to reveal the differentially expressed ARGs in cancer-related biological processes and pathways. Multivariate Cox analysis was used to integrate the ARG nomogram with the ARG signature and clinicopathological information. The nomogram exhibited proper calibration and discrimination (C-index?=?0.75, AUC?=?>0.7). Decision curve analysis also showed that the nomogram was clinically useful.

Conclusions

KIRC patients and doctors could benefit from ARG nomogram use in clinical practice.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7910047 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Development of an Autophagy-Related Gene Prognostic Model and Nomogram for Estimating Renal Clear Cell Carcinoma Survival.

Wang Ying Y Yao Yinhui Y Zhao Jingyi J Cai Chunhua C Hu Junhui J Zhao Yanwu Y

Journal of oncology 20210218

<h4>Background</h4>Kidney renal clear cell carcinoma (KIRC) is a fatal malignancy of the urinary system. Autophagy is implicated in KIRC occurrence and development. Here, we evaluated the prognostic value of autophagy-related genes (ARGs) in kidney renal clear cell carcinoma.<h4>Materials and methods</h4>We analyzed RNA sequencing and clinical KIRC patient data obtained from TCGA and ICGC to develop an ARG prognostic signature. Differentially expressed ARGs were further evaluated by functional a ...[more]

PMID: 33679977

Similar Datasets

Project description:Background: Clear cell renal cell carcinoma (ccRCC) is a common type of malignant tumors in urinary system. Evaluating the prognostic outcome at the time of initial diagnosis is essential for patients. Autophagy is known to play a significant role in tumors. Here, we attempted to construct an autophagy-related prognostic risk signature based on the expression profile of autophagy-related genes (ARGs) for predicting the long-term outcome and effect of precise treatments for ccRCC patients. Methods: We obtained the expression profile of ccRCC from the cancer genome atlas (TCGA) database and extract the portion of ARGs. We conducted differentially expressed analysis on ARGs and then performed enrichment analyses to confirm the anomalous autophagy-related biological functions. Then, we performed univariate Cox regression to screen out overall survival (OS)-related ARGs. With these genes, we established an autophagy-related risk signature by least absolute shrinkage and selection operator (LASSO) Cox regression. We validated the reliability of the risk signature with receiver operating characteristic (ROC) analysis, survival analysis, clinic correlation analysis, and Cox regression. Then we analyzed the function of each gene in the signature by single-gene gene set enrichment analysis (GSEA). Finally, we analyzed the correlation between our risk score and expression level of several targets of immunotherapy and targeted therapy. Results: We established a seven-gene prognostic risk signature, according to which we could divide patients into high or low risk groups and predict their outcomes. ROC analysis and survival analysis validated the reliability of the signature. Clinic correlation analysis found that the risk group is significantly correlated with severity of ccRCC. Multivariate Cox regression revealed that the risk score could act as an independent predictor for the prognosis of ccRCC patients. Correlation analysis between risk score and targets of precise treatments showed that our risk signature could predict the effects of precise treatment powerfully. Conclusion: Our study provided a brand new autophagy-related seven-gene prognostic risk signature, which could perform as a prognostic indicator for ccRCC. Meanwhile, our study provides a novel sight to understand the role of autophagy and suggest therapeutic strategies in the category of precise treatment in ccRCC.

Project description:Abnormal autophagic levels have been implicated in the pathogenesis of multiple cancers, however, its role in tumors is complex and has not yet been explored clearly. Hence, we aimed to explore the prognostic values of autophagy-related genes (ARGs) for kidney renal clear cell carcinoma (KIRC). Differentially expressed ARGs and transcription factors (TFs) were identified in KIRC patients obtaining from the The Cancer Genome Atlas (TCGA) database. Then, networks between TFs and ARGs, gene ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted. Next, we performed consensus clustering, COX regression analysis and Lasso regression analysis to identify the prognostic ARGs. Finally, an individual prognostic index (PI, riskScore) was established. Based on TCGA cohort and ArrayExpress cohort, Survival analysis, ROC curve, independent prognostic analysis, and clinical correlation analysis were also performed to evaluate this PI. Based on differentially expressed ARGs, KIRC patients were successfully divided into two clusters (P = 5.916e-04). AS for PI, it was constructed based on 11 ARGs and significantly classified KIRC patients into high-risk group and low-risk group in terms of OS (P = 4.885e-15 for TCGA cohort, P = 6.366e-03 for ArrayExpress cohort). AUC of its ROC curve reached 0.747 for TCGA cohort and 0.779 for ArrayExpress cohort. What's more, this PI was proven to be a valuable independent prognostic factor in both univariate and multivariate COX regression analysis (P < .001). Prognostic nomograms were also performed to visualize the relationship between individual predictors and survival rates in patients with KIRC. By means of connectivity map database, emetine, cephaeline and co-dergocrine mesilate related to ARGs were found to be negatively correlated with KIRC. This study provided an effective PI for KIRC and also displayed networks between TFs and ARGs. KIRC patients were successfully divided into two clusters based on differentially expressed ARGs. Besides, small molecule drugs related to ARGs were also identified for KIRC.

Project description:BackgroundAs the main histological subtype of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) places a heavy burden on health worldwide. Autophagy-related long non-coding RNAs (ARlncRs) have shown tremendous potential as prognostic signatures in several studies, but the relationship between them and ccRCC still has to be demonstrated.MethodsThe RNA-sequencing and clinical characteristics of 483 ccRCC patients were downloaded download from the Cancer Genome Atlas and International Cancer Genome Consortium. ARlncRs were determined by Pearson correlation analysis. Univariate and multivariate Cox regression analyses were applied to establish a risk score model. A nomogram was constructed considering independent prognostic factors. The Harrell concordance index calibration curve and the receiver operating characteristic analysis were utilized to evaluate the nomogram. Furthermore, functional enrichment analysis was used for differentially expressed genes between the two groups of high- and low-risk scores.ResultsA total of 9 SARlncRs were established as a risk score model. The Kaplan-Meier survival curve, principal component analysis, and subgroup analysis showed that low overall survival of patients was associated with high-risk scores. Age, M stage, and risk score were identified as independent prognostic factors to establish a nomogram, whose concordance index in the training cohort, internal validation, and external ICGC cohort was 0.793, 0.671, and 0.668 respectively. The area under the curve for 5-year OS prediction in the training cohort, internal validation, and external ICGC cohort was 0.840, 0.706, and 0.708, respectively. GO analysis and KEGG analysis of DEGs demonstrated that immune- and inflammatory-related pathways are likely to be critically involved in the progress of ccRCC.ConclusionsWe established and validated a novel ARlncRs prognostic risk model which is valuable as a potential therapeutic target and prognosis indicator for ccRCC. A nomogram including the risk model is a promising clinical tool for outcomes prediction of ccRCC patients and further formulation of individualized strategy.

Dataset Information

Development of an Autophagy-Related Gene Prognostic Model and Nomogram for Estimating Renal Clear Cell Carcinoma Survival.

Background

Materials and methods

Results

Conclusions

Publications

Development of an Autophagy-Related Gene Prognostic Model and Nomogram for Estimating Renal Clear Cell Carcinoma Survival.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets