Abstract 6306: Genomic analysis markers of stemness in oral cancer progression

Abstract

Abstract Introduction: In clinical cancer treatment there is an continuing effort to identify limited gene sets from high dimensional data to predict risk, treatment response, etc. Oral carcinogenesis is a multistep process of mutations, disordered growth, and the development of invasion. In the oral cancer milieu, inflammation and stemness has been demonstrated to be cooperative during carcinogenesis. We hypothesized that differences in inflammation, stemness, and EMT might distinguish lesion and adjacent normal mucosa in our RNA Seq data on preneoplastic lesions. Once candidate genes are identified they might be applied to other oral mucosal specimens to identify risk for malignancy development. Materials and Methods: We collected lesion and adjacent normal mucosal tissues from 16 subjects with high risk leukoplakia and early oral cancer (T1N0 and T2N0). Sequencing libraries were generated using the Illumina Truseq Stranded mRNA library prep kit. Sequencing was performed on an Illumina Hiseq 3000 instrument with paired-end 75bp read and sequenced to an overall depth of 30 million reads per sample. Results: After developing a biospecimen collection procedure that functions in the senior author’s clinic flow, we were able to isolate sequenceable total RNA from 100% of the specimens we collected. We identified several hundred differentially expressed genes between lesion and adjacent normal. With regard to stemness, inflammation, and EMT we multiple candidate genes that could be incorporated into a limited gene set for further studies. Aldehyde dehydrogenase family members were of particular interest in the stemness candidate genes, for example. ALD 1A1 and ALD 3B1, were significantly upregulated in lesion versus normal (P< 0.02). Conclusions: We conclude there are differentially expressed inflammatory, EMT, and stemness in oral preneoplastic specimens. We have identified multiple candidate genes that could be assembled into a limited gene panel (12-24 genes) for further studies of oral cancer risk in mucosal lesions Citation Format: Gretchen Unger, Beverly G. Wuertz, Patrick Gaffney, Frank G. Ondrey. Genomic analysis markers of stemness in oral cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6306.