Abstract 1499: HOXC6 gene functions as an oncogenic driver in HPV+ head and neck squamous cell carcinoma (HNSCC)

Abstract

Abstract Homeobox C6 (HOXC6) belongs to the member of the homeobox family, a highly conserved transcription factor that plays an essential role in morphogenesis and cellular differentiation during embryonic development. Previous studies reported that the dysregulation of HOXC6 gene expression plays a crucial role in carcinogenesis. HOXC6 is reportedly over-expressed in several types of human cancer, including breast, leukemia, and lung cancers. Moreover, higher expression of HOXC6 leads to lymph node metastasis. In addition, it has been also demonstrated that in prostate cancer cells, HOXC6 downregulation reduced cell proliferation by inducing apoptosis. Although the precise mechanisms of HOXC6 in carcinogenesis still need to be investigated. In a secondary data analysis from our previous study, we identified HOXC6 is upregulated and enriched with tumor type-specific enhancer region in HPV+HNSCC samples. Moreover, we used publicly available TCGA data consisting of 520 HNSCC samples and a JHU cohort with 47 HPV+ HNSCC samples to illustrate that HOXC6 is more highly expressed in HPV+ HNSCC than in adjacent normal samples. We further validated the HOXC6 overexpression through an in vitro study using HPV+HNSCC cell lines and patient tissue samples. Clinicopathological data from TCGA indicated that higher HOXC6 expression correlated with poor overall survival. To explore the function of HOXC6 in HNSCC, we knocked down HOXC6 in HPV+ HNSCC cells via siRNA and performed the cell proliferation assay. We observed that HOXC6 downregulation decreased the cell proliferation rate compared to control samples. In conclusion, our results suggest HOXC6 acts as an oncogenic driver in HPV+ HNSCC progression, which is potentially regulated by tumor type-specific enhancers and may serve as a potential biomarker. Citation Format: Subhendu Roy Choudhury, Vera Mukhina, Iuliia Vyshkvorkina, Jessica Gore, Alexa Anderson, Daria A. Gaykalova. HOXC6 gene functions as an oncogenic driver in HPV+ head and neck squamous cell carcinoma (HNSCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1499.