A Pan-Cancer Transcriptomic Signature for Conserved Molecular Programs Underlying Premalignant-Malignant Progression...

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Oral squamous cell carcinoma (OSCC) often develops from oral potentially malignant disorders (OPMDs).
• Predictive molecular biomarkers for malignant transformation in OPMDs are currently limited.
• Conserved transcriptional pathways across epithelial cancers may offer insights into early oral tumorigenesis.

Purpose of the Study:

• To identify shared transcriptional signatures across various carcinomas.
• To evaluate the applicability of these signatures to the progression from precancerous lesions to carcinoma.
• To discover novel biomarkers for early detection and risk stratification of oral precancer.

Main Methods:

• Utilized bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) for five carcinoma types.
• Identified shared differentially expressed genes (DEGs) using stringent statistical criteria.
• Analyzed independent Gene Expression Omnibus (GEO) datasets with premalignant and malignant samples, including OPMD and OSCC cohorts.

Main Results:

• A conserved 45-gene signature was identified, enriched in transcriptional regulation and chromatin organization pathways.
• Key regulatory genes (e.g., ZIC5, MYBL2) and cancer-testis antigens were significantly upregulated.
• Thirteen genes showed consistent dysregulation from normal tissue through OPMD to OSCC, indicating stable biomarker potential.

Conclusions:

• Identified conserved transcriptional programs across epithelial cancers that are also detectable in OPMDs.
• These conserved programs highlight promising biomarker candidates for early oral precancer detection.
• Findings address a critical need for improved risk stratification and management of OSCC.