Integrative transcriptomic analysis for linking acute stress responses to squamous cell carcinoma development

Area of Science:

• Dermatology
• Oncology
• Molecular Biology

Background:

• Cutaneous squamous cell carcinoma (cuSCC) is the second most common skin cancer.
• Chronic UV exposure and wounds are primary risk factors for cuSCC development.

Purpose of the Study:

• To identify overlapping molecular signatures between acute UV exposure, skin wounding, and cuSCC.
• To uncover common pathways and potential drivers contributing to cuSCC initiation and progression.

Main Methods:

• Transcriptomic analysis of acutely UV-exposed human skin.
• Integration of transcriptomic data from wounded skin and cuSCC tumors.
• Functional pair analysis, Gene Set Enrichment Analysis (GSEA), and pathway analysis.

Main Results:

• Significant molecular overlap was identified between UV-exposed skin, wounded skin, and cuSCC datasets.
• Oncostatin M (OSM) was identified as a potential common upstream driver of cuSCC.
• OSM expression correlated with poorer survival in head and neck SCC patients and promoted keratinocyte invasiveness and suppressed apoptosis in vitro.

Conclusions:

• Integrated analysis highlights shared molecular pathways in cuSCC development.
• OSM is a potential therapeutic target for inhibiting cuSCC progression.
• An integrated, biologically-informed approach can identify key tumorigenesis promoters.