Mapping cancer dynamics from normal tissue to malignancy using N- and T-gene expression markers

Area of Science:

• Genomics
• Cancer Biology
• Bioinformatics

Background:

• Carcinogenesis progresses through somatic evolution and tumor progression.
• Standard methods struggle to differentiate these two phases of cancer development.
• N- and T-genes are proposed as novel markers for these distinct carcinogenic phases.

Purpose of the Study:

• To identify and characterize N- and T-genes using TCGA RNA-Seq data.
• To develop a framework for mapping the dynamics of normal tissue evolution and tumor progression.
• To enable a molecular taxonomy of normal and tumor samples.

Main Methods:

• Utilized TCGA RNA-Seq data from prostate adenocarcinoma, lung adenocarcinoma, and liver hepatocellular carcinoma.
• Identified N- and T-genes based on statistically significant exclusive expression intervals in normal and tumor samples.
• Discretized gene expression and analyzed gene counts to infer pseudo-temporal coordinates for somatic evolution and tumor progression.

Main Results:

• Discovered distinct gene expression attractors for normal and tumor samples, yielding large sets of N- and T-genes.
• Observed a continuous decrease in active N-genes and increase in active T-genes during carcinogenesis.
• Demonstrated that N- and T-gene activity counts provide a measure of somatic evolution and tumor progression, respectively.

Conclusions:

• The N- and T-gene framework naturally decomposes carcinogenesis into somatic evolution and tumor progression.
• Active N- and T-gene counts serve as indicators for these distinct phases.
• Gene panels facilitate sample taxonomy and identification of active biological programs across cancer types.