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

Kimia Sadat Kazemi1, Marta Miyazawa2, João Adolfo Costa Hanemann2

  • 1College of Dentistry, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.

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Summary
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Researchers identified a 45-gene signature conserved across epithelial cancers, applicable to oral potentially malignant disorders (OPMDs). This discovery offers potential biomarkers for early oral cancer detection and risk stratification.

Keywords:
biomarker discoverycancer-testis antigens (MAGEA family)early cancer detectiongene expression signaturesmalignant transformationoral potentially malignant disorders (OPMDs)oral squamous cell carcinoma (OSCC)pan-cancer transcriptomicspremalignant lesionstranscriptional regulation

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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.