Factors related to tumor response rate from TCGA three omics data—variants, expression, methylation

Abstract

The Cancer Genome Atlas (TCGA) and its patient-derived multi-omics datasets have been the backbone of cancer research, and with novel approaches, it continues to shed new insight into the disease. In this study, we delved into a method of multi-omics integration of patient datasets and the association of biological pathways related to the disease. First, across thirty-three types of cancer present in TCGA, we merged genomic mutations and drug response datasets and filtered for the viable variant-drug response combinations available in TCGA, containing more than three samples for each drug response label with RNA sequencing (RNA-seq) and genomic methylation data available for each patient. We identified two distinct combinations in TCGA, one being pancreatic adenocarcinoma patients with/without rs121913529 variant in KRAS gene treated with gemcitabine, and the other low-grade glioma with/without rs121913500 variant in IDH1 gene administered with temozolomide. In these two groups, different patterns of gene expression were observed in the pathways often associated with cancer progression, such as mTOR and PDGF between the patients with complete response and progressive disease. Our result will provide yet another example of the relevance of these biological pathways in cancer drug response and a way for multi-omics integration in cancer datasets.

Keywords:

• Cancer
• variants
• tumor response rate
• gene expression
• DNA methylation

Disclosure statement

This research presented the results of a study conducted as part of the “Introduction to Genetic Epidemiology” class at Korea University School of Medicine, where J.-A.G. is the professor in charge and H.-M.A., I.P., and C.G.K. are students. Y.K.K. declared no conflict of interest.

Data availability statement

All data were collected from public data sources. All source codes will provided to the corresponding author upon request.

Additional information

Funding

This research was supported by the National Research Foundation (NRF) funded by the Ministry of Education (grant number: RS-2023-00246906).