Abstract

Clinical Cancer Research via Integration of Next Generation Sequencing and Proteomic Technologies in Taiwanese Oral Squamous Cell Carcinoma

Yu-Sun Chang, Chair Professor, Graduate Institute of Biomedical Sciences, and Molecular Medicine Research Center, Chang Gung University

Oral squamous cell carcinoma (OSCC) is a prominent cancer worldwide, particularly in Taiwan. By integrating omics analyses in 50 matched samples, we uncover in Taiwanese patients a predominant mutation signature associated with cytidine deaminase APOBEC, which correlates with the up-regulation of APOBEC3A expression in the APOBEC3 gene cluster at 22q13. APOBEC3A expression is significantly higher in tumors carrying APOBEC3B-deletion allele(s). High-level APOBEC3A expression is associated with better overall survival, especially among patients carrying APOBEC3B-deletion alleles, as examined in a second cohort (n=188; p=0.004).  Interestingly, the high frequency (50%) of APOBEC3B-deletion alleles is detected in OSCC-Taiwan samples, but not in OSCC-TCGA samples (5.8%, n= 314). Through the integrated omics analyses, we thus identify a frequent APOBEC mutational profile, which relates to a APOBEC3B-deletion germline polymorphism in Taiwanese OSCC that impacts expression of APOBEC3A, and is shown to be of clinical prognostic relevance. Our study emphasizes the importance of integration of multiple omics data for cancer precision medicine research in the future.