Abstract 2169: NAD(P)H: quinone oxidoreductase 1 (NQO1)- A viable biomarker in colorectal cancer

Abstract

Abstract Background/Objective: Colorectal cancer (CRC) is aggressive and widespread (3rd among malignancies) in the United States. NAD(P)H: Quinone Oxidoreductase 1 (NQO1) is an enzyme that contributes to chemoprotection for CRC. The aim of this meta-analysis is to test the connection between NQO1 C609T polymorphisms and CRC risk. Furthermore, the study explores the binding capacity and efficacy of BBI 608 against NQO1 in CRC through molecular docking. The inhibitor will then be tested in vitro. Methods: PubMed, Web of Science, and Google Scholar were used in bibliographic searches. For the NQO1 C609T analysis, a total of 18 studies were used. Data was gathered and subsequently calculated using the pooled odds ratio (OR) (95% confidence interval, CI). Molecular docking, Western Blot and QRT-PCR were used to determine the molecular function of BBI 608 and NQO1. Results: The relation between NQO1 polymorphism and CRC risk (TT + CT vs. CC: OR=1.19, 95% CI =1.06-1.34, p<0.001) was significant. Furthermore, stratified investigation based on ethnicity indicated significant association between NQO1 polymorphism and CRC risk (TT + CT vs. CC: OR=1.17, 95% CI =1.08-1.27, p<0.001). This study indicates that the C609T polymorphism of NQO1 is linked with CRC risk in Asians and Caucasians. To observe the molecular properties of BBI 608 (NQO1 inhibitor) and to analyze the exact mechanism of NQO1 on CRC, computational approaches were applied. This investigation provides a detailed understanding of the interaction between NQO1 and BBI 608 and its implication in CRC therapy. To support this computational analysis, in vitro studies were performed. BBI 608 creates higher cytotoxicity in a dose dependent manner in CRC cell lines. BBI 608 treatment significantly (p<0.001) reduced the NQO1 expression at protein and messenger levels in both CRC (HCT 116 and RKO) cell lines. Conclusion: Based on meta-analysis and computational approach, NQO1 is a viable biomarker and targeted molecule in CRC. In vitro results showed that inhibiting NQO1 with the drug BBI 608 decreased cell proliferation in both CRC cell lines. Knockout or overexpression or site directed mutagenesis is essential for a better understanding about BBI 608 targeted NQO1 and its amino acids. Citation Format: Chaithanya Ganji, Bhaskar VK Lakkakula, Santosh Kumar Behera, Bassel F. El-Rayes. NAD(P)H: quinone oxidoreductase 1 (NQO1)- A viable biomarker in colorectal cancer [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 2169.