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pmid:32219036

Identification of a three-m6A related gene risk score model as a potential prognostic biomarker in clear cell renal cell carcinoma.

Yiqiao Zhao · Zijia Tao · Xiaonan Chen

PeerJ · 2020 doi:10.7717/peerj.8827

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Identification of a three-m6A related gene risk score model as a potential prognostic biomarker in clear cell renal cell carcinoma.
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Yiqiao Zhao
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Zijia Tao
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Xiaonan Chen
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2020
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BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignancies worldwide, N6-methyladenosine (m6A) has been shown to play important roles in regulating gene expression and phenotypes in both health and disease. Here, our purpose is to construct a m6A-regulrator-based risk score (RS) for prediction of the prognosis of ccRCC. METHODS: We used clinical and expression data of m6A related genes from The Cancer Genome Atlas (TCGA) dataset and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis to develop an RS to predict survival of patients with ccRCC, and analyzed correlations between RS and other clinical indicators such as age, grade and stage. Validation of this RS was then engaged in another cohort, E-MTAB-1980 from the ArrayExpress dataset. Finally, we used quantitative real-time PCR to analyze the expression profile of genes consists of the RS. RESULTS: A three-gene RS including METTL3, METTL14 and HNRNPA2B1 which can predict overall survival (OS) of ccRCC patients from TCGA. After applying this RS into the validation cohort from Arrayexpress, we found that it successfully reproduced the result; furthermore, the results of PCR validation were in line with our analysis. CONCLUSION: To sum up, our study has identified an RS composed of m6A related genes that may predict the prognosis of ccRCC patients, which might be helpful for future therapeutic strategies. Our results call for further experimental studies for validations.
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We used clinical and expression data of m6A related genes from The Cancer Genome Atlas (TCGA) dataset and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis to develop an RS to predict survival of patients with ccRCC, and analyzed correlations between RS and other clinical indicators such as age, grade and stage.
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We used clinical and expression data of m6A related genes from The Cancer Genome Atlas (TCGA) dataset and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis to develop an RS to predict survival of patients with ccRCC, and analyzed correlations between RS and other clinical indicators such as age, grade and stage.
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Data AvailabilityThe following information was supplied regarding data availability:The RNA-seq transcriptome data and corresponding clinicopathological information of the training cohort were obtained from TCGA: TCGA-KIRC: cases.project.project_id; HTSeq - FPKM: files.analysis.workflow_typ; Gene Expression Quantification: files.data_category; transcriptome profiling: files.data_type; TCGA-KIRC: cases.project.project_id; clinical: files.data_category; bcr xml: files.data_format. For the RNA-seq data, Fragments Per Kilobase of transcript per Million mapped reads (FPKM) values were obtained for the TCGA-KIRC samples.The validation cohort data is also available at ArrayExpress: E-MTAB-1980.The raw data is also available in the Supplemental Files. The raw data includes validation by qRT-PCR of expression of HNRNPA2B1, METTL3 and METTL14 in 16 pairs of ccRCC samples and matched adjacent normal kidney tissues (n = 32).
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Data AvailabilityThe following information was supplied regarding data availability:The RNA-seq transcriptome data and corresponding clinicopathological information of the training cohort were obtained from TCGA: TCGA-KIRC: cases.project.project_id; HTSeq - FPKM: files.analysis.workflow_typ; Gene Expression Quantification: files.data_category; transcriptome profiling: files.data_type; TCGA-KIRC: cases.project.project_id; clinical: files.data_category; bcr xml: files.data_format. For the RNA-seq data, Fragments Per Kilobase of transcript per Million mapped reads (FPKM) values were obtained for the TCGA-KIRC samples.The validation cohort data is also available at ArrayExpress: E-MTAB-1980.The raw data is also available in the Supplemental Files. The raw data includes validation by qRT-PCR of expression of HNRNPA2B1, METTL3 and METTL14 in 16 pairs of ccRCC samples and matched adjacent normal kidney tissues (n = 32).
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Data AvailabilityThe following information was supplied regarding data availability:The RNA-seq transcriptome data and corresponding clinicopathological information of the training cohort were obtained from TCGA: TCGA-KIRC: cases.project.project_id; HTSeq - FPKM: files.analysis.workflow_typ; Gene Expression Quantification: files.data_category; transcriptome profiling: files.data_type; TCGA-KIRC: cases.project.project_id; clinical: files.data_category; bcr xml: files.data_format. For the RNA-seq data, Fragments Per Kilobase of transcript per Million mapped reads (FPKM) values were obtained for the TCGA-KIRC samples.The validation cohort data is also available at ArrayExpress: E-MTAB-1980.The raw data is also available in the Supplemental Files. The raw data includes validation by qRT-PCR of expression of HNRNPA2B1, METTL3 and METTL14 in 16 pairs of ccRCC samples and matched adjacent normal kidney tissues (n = 32).
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We used clinical and expression data of m6A related genes from The Cancer Genome Atlas (TCGA) dataset and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis to develop an RS to predict survival of patients with ccRCC, and analyzed correlations between RS and other clinical indicators such as age, grade and stage.
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Data AvailabilityThe following information was supplied regarding data availability:The RNA-seq transcriptome data and corresponding clinicopathological information of the training cohort were obtained from TCGA: TCGA-KIRC: cases.project.project_id; HTSeq - FPKM: files.analysis.workflow_typ; Gene Expression Quantification: files.data_category; transcriptome profiling: files.data_type; TCGA-KIRC: cases.project.project_id; clinical: files.data_category; bcr xml: files.data_format. For the RNA-seq data, Fragments Per Kilobase of transcript per Million mapped reads (FPKM) values were obtained for the TCGA-KIRC samples.The validation cohort data is also available at ArrayExpress: E-MTAB-1980.The raw data is also available in the Supplemental Files. The raw data includes validation by qRT-PCR of expression of HNRNPA2B1, METTL3 and METTL14 in 16 pairs of ccRCC samples and matched adjacent normal kidney tissues (n = 32).
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We used clinical and expression data of m6A related genes from The Cancer Genome Atlas (TCGA) dataset and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis to develop an RS to predict survival of patients with ccRCC, and analyzed correlations between RS and other clinical indicators such as age, grade and stage.
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Here, our purpose is to construct a m6A-regulrator-based risk score (RS) for prediction of the prognosis of ccRCC.\nMETHODS: We used clinical and expression data of m6A related genes from The Cancer Genome Atlas (TCGA) dataset and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis to develop an RS to predict survival of patients with ccRCC, and analyzed correlations between RS and other clinical indicators such as age, grade and stage. Validation of this RS was then engaged in another cohort, E-MTAB-1980 from the ArrayExpress dataset. Finally, we used quantitative real-time PCR to analyze the expression profile of genes consists of the RS.\nRESULTS: A three-gene RS including METTL3, METTL14 and HNRNPA2B1 which can predict overall survival (OS) of ccRCC patients from TCGA. After applying this RS into the validation cohort from Arrayexpress, we found that it successfully reproduced the result; furthermore, the results of PCR validation were in line with our analysis.\nCONCLUSION: To sum up, our study has identified an RS composed of m6A related genes that may predict the prognosis of ccRCC patients, which might be helpful for future therapeutic strategies. 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