Oncocytoma-Related Gene Signature to Differentiate Chromophobe Renal Cancer and Oncocytoma Using Machine Learning.

Journal: Cells
PMID: 35053403

Abstract

Publicly available gene expression datasets were analyzed to develop a chromophobe and oncocytoma related gene signature (COGS) to distinguish chRCC from RO. The datasets GSE11151, GSE19982, GSE2109, GSE8271 and GSE11024 were combined into a discovery dataset. The transcriptomic differences were identified with unsupervised learning in the discovery dataset (97.8% accuracy) with density based UMAP (DBU). The top 30 genes were identified by univariate gene expression analysis and ROC analysis, to create a gene signature called COGS. COGS, combined with DBU, was able to differentiate chRCC from RO in the discovery dataset with an accuracy of 97.8%. The classification accuracy of COGS was validated in an independent meta-dataset consisting of TCGA-KICH and GSE12090, where COGS could differentiate chRCC from RO with 100% accuracy. The differentially expressed genes were involved in carbohydrate metabolism, transcriptomic regulation by TP53, beta-catenin-dependent Wnt signaling, and cytokine (IL-4 and IL-13) signaling highly active in cancer cells. Using multiple datasets and machine learning, we constructed and validated COGS as a tool that can differentiate chRCC from RO and complement histology in routine clinical practice to distinguish these two tumors.

Authors

  • Khaled Bin Satter
    Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120 15th Str., Augusta, GA 30912, USA.
  • Paul Minh Huy Tran
    Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120 15th Str., Augusta, GA 30912, USA.
  • Lynn Kim Hoang Tran
    Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120 15th Str., Augusta, GA 30912, USA.
  • Zach Ramsey
    Department of Pathology, Medical College of Georgia, Augusta University, 1120 15th Str., Augusta, GA 30912, USA.
  • Katheine Pinkerton
    Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120 15th Str., Augusta, GA 30912, USA.
  • Shan Bai
    Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120 15th Str., Augusta, GA 30912, USA.
  • Natasha M Savage
    Department of Pathology, Medical College of Georgia, Augusta University, 1120 15th Str., Augusta, GA 30912, USA.
  • Sravan Kavuri
    Department of Pathology, Medical College of Georgia, Augusta University, 1120 15th Str., Augusta, GA 30912, USA.
  • Martha K Terris
    Department of Urology, Medical College of Georgia, Augusta University, 1120 15th Str., Augusta, GA 30912, USA.
  • Jin-Xiong She
    Professor and Director of the Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA.
  • Sharad Purohit
    Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120 15th Str., Augusta, GA 30912, USA.

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