Abstract 2430: HOXC6 promotes tumorigenesis of right-sided colon cancer

Abstract

Abstract Colorectal cancer (CRC) is a common malignant tumor of the digestive tract, with high heterogeneity. The significant difference in prognosis and therapeutic response of left and right colon cancer is a hot spot in the field of colorectal cancer (CRC) in recent years. The prognosis and drug response of right-sided colon cancer were significantly worse than that of the left-sided colon cancer. Clinical trials have proved that MSI-H colon cancer is mainly seen in the right-sided colon cancer, and the prognosis is better than that of MSS. Because MSS and MSI-H patients have different molecular characteristics and prognosis, we searched for key genes of RCC and LCC in MSS and MSI-H groups respectively. The difference between the prognosis and the curative effect of the left and right-sided colon cancer is essentially the difference between the molecular pathology and the immune environment. Therefore, the aim of this study is to explore the molecular mechanism related to the prognosis of left and right-sided colon cancer in order to provide a molecular target for accurate treatment of left and right-sided colon cancer. First of all, bioinformatics methods were used to screen the right and left-sided CRC differentially expressed genes in MSS and MSI-H. The expression levels of these key genes in clinical samples and cell lines were detected by RT-qPCR and IHC, and their correlation with survival prognosis was analyzed. Homeobox C6(HOXC6)were selected. First, HOXC6 stable overexpressed and knockout colorectal cancer cell lines were established and its biological function was preliminarily studied, including transwell, wound-healing assay and CCK-8 tests. Finally, the ChIP-seq data were used to analyze the carcinogenic mechanism of HOXC6. Bioinformatics methods were used to screen 30 differentially expressed genes in MSS right and left CRC, of which HOXC6 in the right colon cancer was significantly higher than that in the left-sided colon cancer, which was positively correlated with TNM staging and lymph node metastasis. Kaplan-Meier survival analysis showed that the expression of HOXC6 was negatively correlated with the total survival of CRC patients (p=0.002). RT-qPCR and IHC showed that the expression of HOXC6 in the right-sided colon cancer was higher than that in the left, P<0.05. Functional experiments showed that Hoxc6 promoted the growth, invasion and migration. ChIP-seq data and real-time PCR results showed that SPOCD1 and S100A1 were the target genes of HOXC6. Citation Format: Xin li, Jinhong Xia, Dengbo Ji, Jin Gu. HOXC6 promotes tumorigenesis of right-sided colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2430.