Pan-organ transcriptome variation across 21 cancer types.

Area of Science:

• Genomics and transcriptomics
• Cancer biology and evolution
• Comparative genomics

Background:

• Messenger RNA (mRNA) conservation across species is established.
• Transcriptome divergence between cancer and normal tissues remains underexplored at a pan-organ level.
• Understanding expression evolution in cancer is crucial for deciphering tumorigenesis.

Purpose of the Study:

• To evaluate expression evolution by analyzing transcriptome divergence between normal and tumor tissues.
• To investigate conserved dysregulations across various cancer types.
• To explore alterations in gene co-regulation networks in cancer.

Main Methods:

• Analysis of a transcriptome sequencing dataset from 675 normal-tumor pairs across 21 solid organs (The Cancer Genome Atlas).
• Assessment of gene expression divergence and organ-specificity.
• Identification of differentially expressed genes and application of weighted gene co-expression network analysis (WGCNA).

Main Results:

• Gene expression divergence and organ-specificity are significantly reduced in most cancer types compared to adjacent normal tissues.
• Cell cycle dysregulation is a common feature across all investigated cancer types.
• Gene modules exhibit substantial structural variations between cancer and normal tissues, indicating disrupted co-regulation.

Conclusions:

• The observed reduction in expression divergence and specificity suggests a loss of regulatory complexity in cancer.
• Disruption of coordinated gene regulatory networks may be a key driver of tumorigenesis and progression.
• Findings offer novel insights into cancer biology and regulatory mechanisms.