Comprehensive genomic and digital pathology profiling of tobacco-chewer female oral cancer patients simultaneously with integration of single-cell datasets identifies clinically actionable patient subgroups Ghosh A, Singh S, Mallick TR, Chakravarty S, Varsha Bhagat S, Das C, Gopinath KS, Mohiyuddin A, Maitra A, Majumder PP, Kundu TK, Biswas NK. Clin Transl Med. 2025 Jul;15(7):e70386. doi: 10.1002/ctm2.70386. PMID: 40621643.
Abstract
Genomic alteration landscape of oral squamous cell carcinoma (OSCC) among female patients remains understudied, although certain regions - southeast Asia, including India, show high burden of OSCC among females. Through generation of whole exome sequencing (WES) and copy-number-array from paired tumour and paired normal tissues, and integrative analysis with digital pathology image from same tumour sections, this study identified somatic alterations associated with differential immune infiltration (identified through applying deep-learning models on whole slide image of tumour H&E) profiles of these tumours. EGFR copy-number amplification status was shown to be significantly associated with low abundance of tumour infiltrating leukocytes (TILs); whereas patient subgroup with CASP8 mutations with co-occurrences of oncogenic somatic mutations in PIK3CA, HRAS, or TP53, shown to have higher abundance of TILs. Large scale publicly available single-cell RNAseq (scRNAseq) data was further utilized to understand the mechanisms of EGFR-driven immune suppression in oral tumours, which led to identification of key epithelial-immune interactions influenced by EGFR amplification and expression. Based on the integrative analysis, clinically actionable subgroups among Indian female OSCC patients, who may be benefitted through repurposing FDA-approved targeted or immunotherapy drugs, some of which are currently available or in clinical-trials.
