Abstract

BackgroundClear-cell Renal Cell Carcinoma (ccRCC) is the most- prevalent, chemotherapy resistant and lethal adult kidney cancer. There is a need for novel diagnostic and prognostic biomarkers for ccRCC, due to its heterogeneous molecular profiles and asymptomatic early stage. This study aims to develop classification models to distinguish early stage and late stage of ccRCC based on gene expression profiles. We employed supervised learning algorithms- J48, Random Forest, SMO and Naïve Bayes; with enriched model learning by fast correlation based feature selection to develop classification models trained on sequencing based gene expression data of RNAseq experiments, obtained from The Cancer Genome Atlas.ResultsDifferent models developed in the study were evaluated on the basis of 10 fold cross validations and independent dataset testing. Random Forest based prediction model performed best amongst the models developed in the study, with a sensitivity of 89%, accuracy of 77% and area under Receivers Operating Curve of 0.8.ConclusionsWe anticipate that the prioritized subset of 62 genes and prediction models developed in this study will aid experimental oncologists to expedite understanding of the molecular mechanisms of stage progression and discovery of prognostic factors for ccRCC tumors.

Highlights

  • Clear-cell Renal Cell Carcinoma is the most- prevalent, chemotherapy resistant and lethal adult kidney cancer

  • Gene expression data matrix The RNAseq dataset for 475 clinically diagnosed Clear-cell Renal Cell Carcinoma (ccRCC) patients were retrieved from TCGA data portal

  • Training-cum-validation We evaluated training models by 10 fold cross-validation for the classifiers trained on the four supervised machine learning algorithms- Sequential Minimal Optimization (SMO), Random Forest, J48 and Naïve Bayes

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Summary

Introduction

Clear-cell Renal Cell Carcinoma (ccRCC) is the most- prevalent, chemotherapy resistant and lethal adult kidney cancer. Renal cell carcinoma is a common adult kidney cancer, accounting for 2-3% of all new cancer cases diagnosed worldwide [1]. Detection of renal cell carcinoma at an early stage is difficult and generally diagnosed incidentally [2]. Nih.gov/) enables systematic studies on genomic, epigenomic and transcriptomic levels for different cancer types that hold clinical and societal importance globally [6]. These projects are making data available to researchers in different levels 1, 2, 3, 4 (i.e. raw, processed, interpreted and summarized respectively) enabling genome informed personalized cancer medicine research [7,8]

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