Cancers in Agreement? Exploring the Cross-Talk of Cancer Metabolomic and Transcriptomic Landscapes Using Publicly Available Data.

Abstract

Simple SummaryChanges in metabolism are a well-known characteristic of cancer cells. Different cancer types are unique in their genetic aspects, but also in their metabolism, which is in turn, governed by genetics. The aim of our study was to find these differences in metabolic behavior across different cancer types and uncovering intersections between gene expression and metabolic deregulations. We scoured the public domain for metabolomics and transcriptomics data from clinical profiling studies to perform a comprehensive comparison study. By combining evidence from both the genetic and the metabolic aspects, we described the most prominently aberrated pathways across eight different cancer types together with their metabolomic and transcriptomics similarities.One of the major hallmarks of cancer is the derailment of a cell’s metabolism. The multifaceted nature of cancer and different cancer types is transduced by both its transcriptomic and metabolomic landscapes. In this study, we re-purposed the publicly available transcriptomic and metabolomics data of eight cancer types (breast, lung, gastric, renal, liver, colorectal, prostate, and multiple myeloma) to find and investigate differences and commonalities on a pathway level among different cancer types. Topological analysis of inferred graphical Gaussian association networks showed that cancer was strongly defined in genetic networks, but not in metabolic networks. Using different statistical approaches to find significant differences between cancer and control cases, we highlighted the difficulties of high-level data-merging and in using statistical association networks. Cancer transcriptomics and metabolomics and landscapes were characterized by changed macro-molecule production, however, only major metabolic deregulations with highly impacted pathways were found in liver cancer. Cell cycle was enriched in breast, liver, and colorectal cancer, while breast and lung cancer were distinguished by highly enriched oncogene signaling pathways. A strong inflammatory response was observed in lung cancer and, to some extent, renal cancer. This study highlights the necessity of combining different omics levels to obtain a better description of cancer characteristics.