Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysis
BackgroundTo comprehensively assess and validate the associations between insulin-like growth factor 2 (IGF2) gene methylation in peripheral blood leukocytes (PBLs) and colorectal cancer (CRC) risk and prognosis.MethodsThe association between IGF2 methylation in PBLs and CRC risk was initially evalu...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.971435/full |
| _version_ | 1827953659289272320 |
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| author | HongRu Sun YanLong Liu YuXue Zhang Yibaina Wang YaShuang Zhao YuPeng Liu |
| author_facet | HongRu Sun YanLong Liu YuXue Zhang Yibaina Wang YaShuang Zhao YuPeng Liu |
| author_sort | HongRu Sun |
| collection | DOAJ |
| description | BackgroundTo comprehensively assess and validate the associations between insulin-like growth factor 2 (IGF2) gene methylation in peripheral blood leukocytes (PBLs) and colorectal cancer (CRC) risk and prognosis.MethodsThe association between IGF2 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 IGF2 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.ResultsPBL IGF2 hypermethylation was associated with an increased risk of CRC in the initial study (ORPS-adjusted, 2.57, 95% CI: 1.65 to 4.03, P<0.0001), and this association was validated using two independent external datasets (ORPS-adjusted, 2.21, 95% CI: 1.28 to 3.81, P=0.0042 and ORPS-adjusted, 10.65, 95% CI: 1.26 to 89.71, P=0.0295, respectively). CRC patients with IGF2 hypermethylation in PBLs had significantly improved overall survival compared to those patients with IGF2 hypomethylation (HRPS-adjusted, 0.47, 95% CI: 0.29 to 0.76, P=0.0019). The prognostic signature was also observed in the EPIC-Italy CRC cohort, although the HR did not reach statistical significance (HRPS-adjusted, 0.69, 95% CI: 0.37 to 1.27, P=0.2359).ConclusionsIGF2 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. |
| first_indexed | 2024-04-09T14:17:00Z |
| format | Article |
| id | doaj.art-11c7c54019bc43f0bdea82e05303775c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-09T14:17:00Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-11c7c54019bc43f0bdea82e05303775c2023-05-05T06:01:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-05-011310.3389/fonc.2023.971435971435Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysisHongRu Sun0YanLong Liu1YuXue Zhang2Yibaina Wang3YaShuang Zhao4YuPeng Liu5Department of Epidemiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Colorectal Surgery, The Third Affiliated Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Hygiene Microbiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Epidemiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Epidemiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Epidemiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang, ChinaBackgroundTo comprehensively assess and validate the associations between insulin-like growth factor 2 (IGF2) gene methylation in peripheral blood leukocytes (PBLs) and colorectal cancer (CRC) risk and prognosis.MethodsThe association between IGF2 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 IGF2 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.ResultsPBL IGF2 hypermethylation was associated with an increased risk of CRC in the initial study (ORPS-adjusted, 2.57, 95% CI: 1.65 to 4.03, P<0.0001), and this association was validated using two independent external datasets (ORPS-adjusted, 2.21, 95% CI: 1.28 to 3.81, P=0.0042 and ORPS-adjusted, 10.65, 95% CI: 1.26 to 89.71, P=0.0295, respectively). CRC patients with IGF2 hypermethylation in PBLs had significantly improved overall survival compared to those patients with IGF2 hypomethylation (HRPS-adjusted, 0.47, 95% CI: 0.29 to 0.76, P=0.0019). The prognostic signature was also observed in the EPIC-Italy CRC cohort, although the HR did not reach statistical significance (HRPS-adjusted, 0.69, 95% CI: 0.37 to 1.27, P=0.2359).ConclusionsIGF2 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.https://www.frontiersin.org/articles/10.3389/fonc.2023.971435/fullIGF2 hypermethylationcolorectal neoplasmsriskprognosispropensity score analysis |
| spellingShingle | HongRu Sun YanLong Liu YuXue Zhang Yibaina Wang YaShuang Zhao YuPeng Liu Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysis Frontiers in Oncology IGF2 hypermethylation colorectal neoplasms risk prognosis propensity score analysis |
| title | Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysis |
| title_full | Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysis |
| title_fullStr | Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysis |
| title_full_unstemmed | Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysis |
| title_short | Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysis |
| title_sort | insulin like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis a propensity score analysis |
| topic | IGF2 hypermethylation colorectal neoplasms risk prognosis propensity score analysis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.971435/full |
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