Abstract 76: Global LINE-1 Hypomethylation as Novel Biomarker for Cervical Cancer in Nigerian Women Living with HIV
Authors: Zheng Yinan , Musa Jonah , Kim Kyeezu , Qu Yishu , Joyce Brian , Wang Jun , Gursel Demirkan , Silas Olugbenga , Fatimah Abdulkareem , Imade Godwin , Akanmu Alani , Wei Jian-Jun , Kocherginsky Masha , Kim Kwang-Youn , Wehbe Firas , Achenbach Chad , Anorlu Rose , Simon Melissa , Sagay Atiene , Ogunsola Folasade , Murphy Robert , Hou Lifang 
Published: July 2021

Abstract
Purpose: Nigeria faces a high health burden of cervical cancer (CC), which is worsened by high prevalence of human immunodeficiency virus (HIV) infection. Repetitive elements (RE) are DNA sequences that occur in multiple copies throughout the human genome. HIV infection can lead to RE hypomethylation that causes genome instability, an event often seen in the early phase of tumorigenesis. We aim to examine global RE hypomethylation as a novel epigenetic biomarker for CC among HIV-positive women in Nigeria.
Methods: This study involved three groups of women: a) HIV-positive with CC (n=39); b) HIV-positive and cancer-free (n=52); and c) HIV-negative with CC (n=23). We estimated three types of global RE methylation in cervical tissue using genome-wide methylation data: long interspersed nuclear elements (LINE-1), Alu, and human endogenous retrovirus (HERV). We used multiple linear regression adjusting for age, education, parity, employment, cancer stage, body mass index, and sample batch to compare the biomarkers across the HIV/ICC groups and paired t-test to compare 26 pairs of tumor vs. surrounding normal tissues, stratified by HIV status. Receiver operating characteristic curve (ROC) and area under the ROC (AUC) were used to examine the diagnostic value.
Results: Among HIV-positive women, all 3 global RE methylation biomarkers were hypomethylated in CC compared to cancer-free (LINE-1: mean difference [MD]=-0.049, p-value=2.9e-8; Alu: MD=-0.011, p-value=2.0e-4; HERV: MD=-0.013, p-value=1.7e-6). Paired analyses showed a larger, more significant MD in HIV-positive stratum than HIV-negative, especially LINE-1 (MD=-0.048 vs. -0.020, p-value=0.004 vs. 0.254). LINE-1 achieved the highest AUC (0.85, 95% CI: 0.76-0.95) in distinguishing tumor tissue from normal tissue among HIV-positive women, followed by HERV (0.82, 95% CI: 0.73-0.92) and Alu (0.60, 95% CI: 0.47-0.72).
Conclusion: Global LINE-1 hypomethylation may serve as a novel biomarker for CC screening and early detection for women living with HIV in low- and middle-income countries.
Citation Format: Yinan Zheng, Jonah Musa, Kyeezu Kim, Yishu Qu, Brian Joyce, Jun Wang, Demirkan Gursel, Olugbenga Silas, Abdulkareem Fatimah, Godwin Imade, Alani Akanmu, Jian-Jun Wei, Masha Kocherginsky, Kwang-Youn Kim, Firas Wehbe, Chad Achenbach, Rose Anorlu, Melissa Simon, Atiene Sagay, Folasade Ogunsola, Robert Murphy, Lifang Hou. Global LINE-1 Hypomethylation as Novel Biomarker for Cervical Cancer in Nigerian Women Living with HIV [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 76.