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Abstract：
BACKGROUND: Despite evidence showing a connection between inflammation and endometrial cancer (EC) risk, the surveys on genetic correlation and cohort studies investigating the impact on long-term outcomes have yet to be refined. We aimed to address the impact of inflammation factors on the pathogenesis, progression and consequences of EC.
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.
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.
摘要：
背景：尽管有证据表明炎症与子宫内膜癌（EC）风险之间存在联系，关于遗传相关性的调查和调查对长期结局影响的队列研究还有待完善.我们旨在解决炎症因素对发病机制的影响，EC的进展和后果。
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。
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。
