METHODS: For the genetic correlation analyses, a two-sample of Mendelian randomization (MR) study was applied to investigate inflammation-related single-nucleotide polymorphisms involved with endometrial cancer from GWAS databases. The observational retrospective study included consecutive patients diagnosed with EC (stage I to IV) with surgeries between January 2010 and October 2020 at the Cancer Hospital of Shantou University Medical College.
RESULTS: The 2-sample MR surveys indicated no causal relationship between inflammatory cytokines and endometrial cancer. 780 cases (median age, 55.0 years ) diagnosed with EC were included in the cohort and followed up for an average of 6.8 years. Increased inflammatory parameters at baseline were associated with a higher FIGO stage and invasive EC risk (odds ratios [OR] 1.01 to 4.20). Multivariate-cox regression suggested that multiple inflammatory indicators were significantly associated with overall survival (OS) and progression-free survival (PFS) (P < 0.05). Nomogram models based on inflammatory risk and clinical factors were developed for OS and PFS with C-index of 0.811 and 0.789, respectively. LASSO regression for the validation supported the predictive efficacy of inflammatory and clinical factors on the long-term outcomes of EC.
CONCLUSIONS: Despite the fact that the genetic surveys did not show a detrimental impact of inflammatory cytokines on the endometrial cancer risk, our cohort study suggested that inflammatory level was associated with the progression and long-term outcomes of EC. This evidence may contribute to new strategies targeted at decreasing inflammation levels during EC therapy.
方法:对于遗传相关性分析,我们采用孟德尔随机化(MR)研究的两个样本,从GWAS数据库中调查与子宫内膜癌相关的炎症相关单核苷酸多态性.观察性回顾性研究包括2010年1月至2020年10月在汕头大学医学院肿瘤医院接受手术的连续诊断为EC(I至IV期)的患者。
结果:2个样本的MR调查显示炎性细胞因子与子宫内膜癌之间没有因果关系。780例(中位年龄,55.0年)诊断为EC的患者被纳入队列,平均随访6.8年。基线炎症参数增加与较高的FIGO分期和侵袭性EC风险相关(比值比[OR]1.01至4.20)。多因素Cox回归分析显示,多个炎症指标与总生存期(OS)和无进展生存期(PFS)显著相关(P<0.05)。基于炎症风险和临床因素,开发了OS和PFS的列线图模型,C指数分别为0.811和0.789。LASSO回归验证支持炎症和临床因素对EC长期结局的预测功效。
结论:尽管基因调查没有显示炎性细胞因子对子宫内膜癌风险的有害影响,我们的队列研究提示炎症水平与EC的进展和长期结局相关.这些证据可能有助于在EC治疗期间降低炎症水平的新策略。