Dataset Information

A Five-Gene Signature Predicts Prognosis in Patients with Kidney Renal Clear Cell Carcinoma.

ABSTRACT: Kidney renal clear cell carcinoma (KIRC) is one of the most common cancers with high mortality all over the world. Many studies have proposed that genes could be used to predict prognosis in KIRC. In this study, RNA expression data from next-generation sequencing and clinical information of 523 patients downloaded from The Cancer Genome Atlas (TCGA) dataset were analyzed in order to identify the relationship between gene expression level and the prognosis of KIRC patients. A set of five genes that significantly associated with overall survival time was identified and a model containing these five genes was constructed by Cox regression analysis. By Kaplan-Meier and Receiver Operating Characteristic (ROC) analysis, we confirmed that the model had good sensitivity and specificity. In summary, expression of the five-gene model is associated with the prognosis outcomes of KIRC patients, and it may have an important clinical significance.

SUBMITTER: Zhan Y

PROVIDER: S-EPMC4619904 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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A Five-Gene Signature Predicts Prognosis in Patients with Kidney Renal Clear Cell Carcinoma.

Zhan Yueping Y Guo Wenna W Zhang Ying Y Wang Qiang Q Xu Xin-jian XJ Zhu Liucun L

Computational and mathematical methods in medicine 20151011

Kidney renal clear cell carcinoma (KIRC) is one of the most common cancers with high mortality all over the world. Many studies have proposed that genes could be used to predict prognosis in KIRC. In this study, RNA expression data from next-generation sequencing and clinical information of 523 patients downloaded from The Cancer Genome Atlas (TCGA) dataset were analyzed in order to identify the relationship between gene expression level and the prognosis of KIRC patients. A set of five genes th ...[more]

PMID: 26539246

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Project description:Background: Oxidative stress is related to oncogenic transformation in kidney renal clear cell carcinoma (KIRC). We intended to identify a prognostic antioxidant gene signature and investigate its relationship with immune infiltration in KIRC. Methods: With the support of The Cancer Genome Atlas (TCGA) database, we researched the gene expression and clinical data of KIRC patients. Antioxidant related genes with significant differences in expression between KIRC and normal samples were then identified. Through univariate and multivariate Cox analysis, a prognostic gene model was established and all patients were divided into high- and low-risk subgroups. Single sample gene set enrichment analysis was adopted to analyze the immune infiltration, HLA expression, and immune checkpoint genes in different risk groups. Finally, the prognostic nomogram model was established and evaluated. Results: We identified six antioxidant genes significantly correlated with the outcome of KIRC patients as independent predictors, namely DPEP1 (HR = 0.97, P < 0.05), GSTM3 (HR = 0.97, P < 0.05), IYD (HR = 0.33, P < 0.05), KDM3B (HR = 0.96, P < 0.05), PRDX2 (HR = 0.99, P < 0.05), and PRXL2A (HR = 0.96, P < 0.05). The high- and low-risk subgroups of KIRC patients were grouped according to the six-gene signature. Patients with higher risk scores had poorer prognosis, more advanced grade and stage, and more abundance of M0 macrophages, regulatory T cells, and follicular helper T cells. There were statistically significant differences in HLA and checkpoint gene expression between the two risk subgroups. The performance of the nomogram was favorable (concordance index = 0.766) and reliably predicted the 3-year (AUC = 0.792) and 5-year (AUC = 0.766) survival of patients with KIRC. Conclusion: The novel six antioxidant related gene signature could effectively forecast the prognosis of patients with KIRC, supply insights into the interaction between cellular antioxidant mechanisms and cancer, and is an innovative tool for selecting potential patients and targets for immunotherapy.

Project description:Clear cell renal cell carcinoma (ccRCC) is considered to be related to the worse prognosis, which might in part be attributed to the early recurrence and metastasis, compared with other type of kidney cancer. Oxidative stress refers to an imbalance between production of oxidants and antioxidant defense. Accumulative studies have indicated that oxidative stress genes contribute to the tumor invasion, metastasis and drug sensitivity. However, the biological functions of oxidative stress genes in ccRCC remain largely unknown. In this study, we identified 1,399 oxidative stress genes from GeneCards with a relevance score ≥7. Data for analysis were accessed from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database, and were utilized as training set and validation set respectively. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox were employed to construct a prognostic signature in ccRCC. Finally, a prognostic signature including four different oxidative stress genes was constructed from 1,399 genes, and its predictive performance was verified through Kaplan-Meier survival analysis and the receiver operating characteristic (ROC) curve. Interestingly, we found that there was significant correlation between the expression of oxidative stress genes and the immune infiltration and the sensitivity of tumor cells to chemotherapeutics. Moreover, the highest hazard ratio gene urocortin (UCN) was chosen for further study; some necessary vitro experiments proved that the UCN could promote the ability of ccRCC proliferation and migration and contribute to the degree of oxidative stress. In conclusion, it was promising to predict the prognosis of ccRCC through the four oxidative stress genes signature. UCN played oncogenic roles in ccRCC by influencing proliferation and oxidative stress pathway, which was expected to be the novel therapeutic target for ccRCC.

Project description:Background: M7G modification is extremely vital for the development of many cancers, especially tumor immunity. M7G modification is a novel functional regulator of miRNA, and the researches on m7G-related miRNAs in kidney renal clear cell carcinoma (KIRC) are still insufficient. This research aims to establish a risk signature on the foundation of m7G-associated miRNAs, which can precisely forecast the prognosis of KIRC patients. Methods: Transcriptome data and clinical data used in this study come from The Cancer Genome Atlas database. Our team utilized univariable Cox, Lasso and multivariable Cox analyses to construct a m7G-associated miRNAs risk signature that can forecast the prognosis of KIRC patients. Kaplan-Meier method, time-dependent receiver operating characteristic (ROC) curve, and the independent analysis of risk signatures were employed to verify the predictability and accuracy of the risk signature. Subsequently, based on CIBERSORT, ESTIMATE and ssGSEA algorithms, we speculated the potential impact of the proposed risk signature on tumor immune microenvironment. Ultimately, by virtue of the risk signature and tumor immunity, the hub genes affecting the prognosis of KIRC patients were screened out. Results: Our team established and verified a prognostic signature comprising 7 m7G-associated miRNAs (miR-342-3p, miR-221-3p, miR-222-3p, miR-1277-3p, miR-6718-5p, miR-1251-5p, and miR-486-5p). The results of the Kaplan-Meier survival analysis revealed that the prognosis of KIRC sufferers in the high-risk group was often unsatisfactory. The accuracy of the prediction ability of the risk signature was verified by calculating the area under the ROC curve. Univariate-multivariate Cox analyses further showed that this risk signature could be utilized as an independent prognosis-related biomarker for KIRC sufferers. The results of the immune analysis revealed that remarkable diversities existed in immune status and tumor microenvironment between high-risk and low-risk groups. On the foundation of the proposed risk signature and other clinical factors, a nomogram was established to quantitatively forecast the survival of KIRC sufferers at 1, 3 and 5 years. Conclusion: Based on m7G-related miRNAs, a risk signature was successfully constructed, which could precisely forecast the prognosis of sufferers and guide personalized immunotherapy for KIRC patients.

Dataset Information

A Five-Gene Signature Predicts Prognosis in Patients with Kidney Renal Clear Cell Carcinoma.

Publications

A Five-Gene Signature Predicts Prognosis in Patients with Kidney Renal Clear Cell Carcinoma.

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