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目的:探讨肿瘤干细胞标记基因LGR5在局部晚期直肠癌新辅助放化疗f放疗同时口服卡培他滨)前后表达的变化,及其对新辅助放化疗效果预测的作用。方法:收集2014年1月—2016年2月在新疆医科大学附属肿瘤医院接受新辅助放化疗并手术治疗的94例局部晚期直肠癌患者临床资料,对其新辅助放化疗前肠镜活检组织及新辅助放化疗后手术切除组织标本采用荧光定量PCR(qPCR)法检测LGR5 mRNA的表达,分析其在新辅助放化疗前后表达水平的变化及其与疗效的关系,采用Kaplan-Meier法进行生存分析,Log-rank法进行单因素预后分析和Cox回归进行多因素预后分析。结果:直肠癌患者接受新辅助放化疗后肿瘤病理退缩反应良好,肿瘤退缩有效率达87.2%,其中病理完全缓解率为18.1%。直肠癌癌组织中LGR5 mRNA的相对表达水平从新辅助放化疗前的14.396±9.924减少到手术后的8.847±6.664,总体表达水平显著下降(P<0.05)。放化疗后LGR5 mRNA表达上调者27例,表达下调者67例,表达下调组肿瘤病理退缩程度(TRG)和1、2年生存率均明显优于表达上调组(P<0.05)。单因素生存分析结果显示放化疗前血清CA19-9水平、临床分期、TRG分级和LGR5 mRNA表达差异为直肠癌预后的影响因素(P均<0.05);多因素分析表明放化疗前CA19-9水平和放化疗前后LGR5 mRNA表达差异是直肠癌预后的影响因素(P分别为0.013和0.015)。结论:新辅助放化疗可以诱导LGR5 mRNA表达的改变,检测其表达对于判断直肠癌预后及指导治疗具有参考价值,新辅助放化疗前后LGR5 mRNA表达变化和放化疗前CA19-9水平有可能成为预测局部晚期直肠癌新辅助放化疗效果的参考指标。
Objective: To investigate the changes of tumor stem cell marker gene LGR5 expression before and after neoadjuvant chemoradiation and radiotherapy combined with capecitabine in locally advanced rectal cancer and its effect on neoadjuvant chemoradiation. Methods: The clinical data of 94 patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy and chemotherapy at the Affiliated Tumor Hospital of Xinjiang Medical University from January 2014 to February 2016 were collected. Their neoadjuvant chemoradiation and colonoscopy before colonoscopy and Neoadjuvant chemoradiotherapy after surgical resection of tissue specimens using quantitative PCR (qPCR) detection of LGR5 mRNA expression before and after neoadjuvant chemoradiation changes in the expression level and its relationship with the efficacy of Kaplan-Meier survival analysis , Log-rank method of univariate prognostic analysis and Cox regression multivariate prognostic analysis. Results: Rectal cancer patients received neoadjuvant chemoradiotherapy after tumor radiotherapy. The effective rate of tumor regression was 87.2%, of which pathological complete remission rate was 18.1%. The relative expression level of LGR5 mRNA in rectal cancer tissues decreased from 14.396 ± 9.924 before neoadjuvant chemoradiation to 8.847 ± 6.664 after neoadjuvant chemotherapy, and the overall expression level was significantly decreased (P <0.05). After chemoradiotherapy, 27 cases were up-regulated in LGR5 mRNA expression, 67 cases were down-regulated. The expression of TRG and 1,2 year survival rate of the down-regulated group were significantly higher than that of the up-regulated group (P <0.05). The results of univariate survival analysis showed that the levels of CA19-9, clinical stage, TRG classification and LGR5 mRNA expression before radiotherapy and chemotherapy were the influencing factors of prognosis of rectal cancer (all P <0.05). Multivariate analysis showed that the level of CA19-9 before radiotherapy and chemotherapy The difference of LGR5 mRNA expression before and after chemoradiotherapy was the prognostic factor of rectal cancer (P = 0.013 and 0.015, respectively). Conclusions: Neoadjuvant chemoradiotherapy can induce the change of LGR5 mRNA expression. Detecting the expression of LGR5 mRNA may be valuable in predicting the prognosis and guiding therapy of rectal cancer. Neonadjuvant chemoradiation and chemotherapy before and after LGR5 mRNA expression and the level of CA19-9 before radiotherapy and chemotherapy may be the predictors Reference index for neoadjuvant chemoradiation in locally advanced rectal cancer.