Abstract 2228: Differential expression of MT-ATPase and COXIV genes in colorectal adenopolyps

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Abstract Therapeutic decisions in colorectal cancer (CRC) will be enhanced if guided by more accurate prognostic and predictive biomarkers during the progression of adenomas to CRC. Given that most CRCs develop from adenopolyps via the adenoma-carcinoma sequence, a mechanism for the inhibition of this sequence in patients with a high risk of developing CRC is a pressing need. Variants in mitochondrial (mt) protein expressions have been correlated with several clinico-pathological features of cancers as the majority of energy for tumor transformation are of mitochondrial origin. Differences in mitochondrial efficiency may be reflected as in adenoma-carcinoma sequence. Reports have shown that cytochrome c oxidase (COX) is a key player in oxidative phosphorylation and reactive oxygen species (ROS) formation. In addition ATPase subunits are also associated with ROS formation and mtDNA maintenance. Here, we specifically searched for differentially expressed ATPase and COX subunits in early adenomas of CRC tissues as compared to late stages of CRC tissues. In addition mitochondria variants were analyzed in mitochondrial encoded subunits of complexes IV and V of the electron transport chain. Direct sequencing, high resolution restriction digestion, RT-qPCR and western blot techniques were used to assess differences in colorectal tumors. Tissue samples used included early adenomas classified as tubular adenoma (TA), tubulovillous adenoma (TV), and villous adenomas (v); cancer tissues, and normal surrounding tissues. Results suggest that most variants of complex IV were found in mitochondrial encoded cytochrome c oxidase subunit III (9207-9990). Of these variants 9414delC found in 60% TA and 20% CA samples was predicted to be disease causing. Furthermore, ATPase6 variant G9055A found abundantly in TA and V samples was confirmed using high resolution restriction digestion. Expression levels of ATPase6 progressively increased from early adenomas to late stage adenomas and cytochrome c oxidase mitochondrial subunits also varied within the adenoma carcinoma sequence. Interestingly, COX subunit 4 isoform 1 protein expression decreased by five-fold in cancer samples when compared to normal tissue and by three-fold when compared to TA. Therefore, this study suggest an important role of ATPase and COX IV-1 in tumor CRC progression in respect to the impact on mitochondrial ROS production and oxidative phosphorylation regulation. Citation Format: Lashanale Wallace, Anju Cherian, Felix Aikhionbare. Differential expression of MT-ATPase and COXIV genes in colorectal adenopolyps [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 2228.