Abstract 2263: The dysregulation of circadian genes across cancers

As the daily oscillation in physiological processes, circadian is critical for health while disruption of the circadian rhythm has been associated with cancer in humans. Generally, circadian rhythm was proposed to play important roles in tumor suppression, while there were also evidences that disruption of canonical circadian pathway have anti-cancer effects. In this study, we systematically analyzed the aberrances including mutation, somatic copy number alternation, differential DNA methylation and differential expression of circadian genes across cancers based on TCGA data. It is observed that core circadian network genes (CCNGs) such as PER1/2/3, CLOCK, CRY1/2, ARNTL were highly mutated in a number of cancers such as uterine corpus endometrial carcinoma, skin cutaneous melanoma, stomach adenocarcinoma and colon adenocarcinoma. Generally, the expression for the majority of CCNGs was down regulated in a variety of the cancers such as bladder urothelial carcinoma, head and neck squamous cell carcinoma, breast invasive carcinoma, cervical and endocervical cancers, prostate adenocarcinoma, glioblastoma multiforme and stomach adenocarcinoma, while the expression of a number of CCNGs were related with overall survival in various cancers. The alternations of somatic copy number and DNA methylation were observed to be consistent with the differential expression of these CCNGs. Furthermore, the PCA based circadian gene expression signature was found to be related with the overall survivals and immunophenotypes among cancers, which indicated that circadian rhythm might play critical roles in regulation of immune signaling state in tumor environment. Taken together, our study provided comprehensive analyses of the aberrances and functional roles of circadian genes in cancer, while the results should be helpful for further investigation of the molecular mechanisms and therapy development for cancer. Citation Format: Zexian Liu, Huan Lin, Zekun Liu, Kai Yu, Qi Zhao, Xiaolong Zhang, Yan Wang, Zhixiang Zuo. The dysregulation of circadian genes across cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2263.