Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas.

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Squamous cell carcinomas (SCCs) are a significant group of cancers.
• Understanding their molecular underpinnings is crucial for developing effective treatments.

Purpose of the Study:

• To identify and characterize the distinct molecular features of SCCs from five anatomical sites.
• To correlate these features with etiological factors like smoking and human papillomavirus (HPV) infection.
• To explore potential therapeutic targets and molecular classification strategies.

Main Methods:

• Integrated analysis of multiplatform data from the PanCancer Atlas.
• Co-mapping of chromosomal copy-number alterations (CNAs), DNA mutations, and gene/microRNA methylation.
• Correlation of molecular alterations with gene expression programs.

Main Results:

• SCCs exhibit recurrent CNAs (e.g., 3q, 5p), mutations, and aberrant methylation.
• Low-CNA SCCs are often HPV(+), showing hypermethylation and mutations in key genes (e.g., TET1, FANCF, CASP8, RAS-MAPK).
• Hypomethylation of the ΔNp63 oncogene promoter and co-expression of immune suppressive cell signatures were observed, potentially impacting immunotherapy efficacy.

Conclusions:

• Distinct molecular profiles differentiate SCCs based on etiology.
• Aberrant molecular pathways, including stemness, differentiation, and immune suppression, are implicated in SCC development.
• These findings support molecular-based classification and novel therapeutic strategies for SCCs.