AUTHOR=Sun HongRu , Liu YanLong , Zhang YuXue , Wang Yibaina , Zhao YaShuang , Liu YuPeng 

TITLE=Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysis

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.971435

DOI=10.3389/fonc.2023.971435

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>To comprehensively assess and validate the associations between insulin-like growth factor 2 (<italic>IGF2</italic>) gene methylation in peripheral blood leukocytes (PBLs) and colorectal cancer (CRC) risk and prognosis.</p></sec><sec><title>Methods</title><p>The association between <italic>IGF2</italic> methylation in PBLs and CRC risk was initially evaluated in a case-control study and then validated in a nested case-control study and a twins’ case-control study, respectively. Meanwhile, an initial CRC patient cohort was used to assess the effect of <italic>IGF2</italic> methylation on CRC prognosis and then the finding was validated in the EPIC-Italy CRC cohort and TCGA datasets. A propensity score (PS) analysis was performed to control for confounders, and extensive sensitivity analyses were performed to assess the robustness of our findings.</p></sec><sec><title>Results</title><p>PBL <italic>IGF2</italic> hypermethylation was associated with an increased risk of CRC in the initial study (OR<sub>PS-adjusted</sub>, 2.57, 95% CI: 1.65 to 4.03, <italic>P</italic>&lt;0.0001), and this association was validated using two independent external datasets (OR<sub>PS-adjusted</sub>, 2.21, 95% CI: 1.28 to 3.81, <italic>P</italic>=0.0042 and OR<sub>PS-adjusted</sub>, 10.65, 95% CI: 1.26 to 89.71, <italic>P</italic>=0.0295, respectively). CRC patients with <italic>IGF2</italic> hypermethylation in PBLs had significantly improved overall survival compared to those patients with <italic>IGF2</italic> hypomethylation (HR<sub>PS-adjusted</sub>, 0.47, 95% CI: 0.29 to 0.76, <italic>P</italic>=0.0019). The prognostic signature was also observed in the EPIC-Italy CRC cohort, although the HR did not reach statistical significance (HR<sub>PS-adjusted</sub>, 0.69, 95% CI: 0.37 to 1.27, <italic>P</italic>=0.2359).</p></sec><sec><title>Conclusions</title><p><italic>IGF2</italic> hypermethylation may serve as a potential blood-based predictive biomarker for the identification of individuals at high risk of developing CRC and for CRC prognosis.</p></sec>