A clonal expression biomarker associates with lung cancer mortality

Area of Science:

• Genomics
• Cancer Biology
• Biomarker Discovery

Background:

• Molecular biomarkers stratify cancer patients, improving diagnostic precision.
• Transcriptomic intratumor heterogeneity (RNA-ITH) confounds existing expression-based biomarkers in multiple cancer types.

Purpose of the Study:

• To explore and control for RNA-ITH in non-small cell lung cancer.
• To identify homogeneous gene expression modules for robust biomarker development.

Main Methods:

• Analysis of multi-region whole-exome and RNA sequencing data from 156 tumor regions in 48 non-small cell lung cancer patients.
• Investigated chromosomal instability as a driver of RNA-ITH.
• Identified homogeneously expressed genes associated with cancer cell proliferation.

Main Results:

• Chromosomal instability is a major driver of RNA-ITH, making current prognostic signatures vulnerable to tumor sampling bias.
• Homogeneously expressed genes form proliferation modules driven by early DNA copy-number gains.
• Clonal transcriptomic biomarkers overcome sampling bias and associate with survival independently of other risk factors.

Conclusions:

• Clonal transcriptomic biomarkers offer a strategy to refine biomarker design across cancer types.
• Addressing RNA-ITH is crucial for developing precise and reliable cancer biomarkers.
• This approach may enhance patient stratification and improve cancer outcome prediction.