结肠癌组织microRNA-223、FBXW7的表达及与其临床病理参数和预后的关系

Expression of microRNA-223 and FBXW7 in colon cancer tissues and relationship with clinicopathological parameters and prognosis

摘要:

目的 研究结肠癌组织中microRNA-223（miR-223）、FBXW7的表达及其与临床病理参数和预后的关系。方法 收集2015年1月—2017年4月钦州市第一人民医院146例经手术切除的结肠癌组织和癌旁组织，采用实时荧光定量聚合酶链反应（qRT-PCR）检测结肠癌组织中miR-223、FBXW7表达。通过在线网站预测miR-223与FBXW7存在结合位点。Pearson法分析两者表达的相关性及其与临床病理参数的关系。根据结肠癌组织中miR-223、FBXW7表达的均值分为miR-223高表达组与miR-223低表达组，FBXW7高表达组与FBXW7低表达组。用Kaplan-Meier法绘制不同miR-223、FBXW7表达结肠癌患者的生存曲线。多因素Cox回归分析结肠癌患者预后的影响因素。结果 结肠癌组织miR-223 mRNA相对表达量高于癌旁组织（P <0.05），FBXW7 mRNA相对表达量低于癌旁组织（P <0.05）。病理分期Ⅲ期、有淋巴结转移结肠癌组织miR-223 mRNA相对表达量高于Ⅰ、Ⅱ期和无淋巴结转移（P <0.05）；病理分期Ⅲ期、有淋巴结转移结肠癌组织FBXW7 mRNA相对表达量低于Ⅰ、Ⅱ期和无淋巴结转移（P <0.05）。不同性别、年龄、肿瘤大小、分化程度及有无侵犯浆膜结肠癌组织miR-223、FBXW7 mRNA相对表达量比较，差异无统计学意义（P >0.05）。Pearson相关系数分析显示，结肠癌组织miR-223表达与FBXW7表达呈负相关（r =-0.679，P <0.05）。术后随访8～60个月，随访期间死亡35例，总生存率为76.03％（111/146）。miR-223高表达组总生存率低于miR-223低表达组（P <0.05）。FBXW7高表达组总生存率高于FBXW7低表达组（P <0.05）。单因素Cox回归分析结果显示，侵犯浆膜［H^R =1.454（95% CI：1.086，1.947）］、病理分期Ⅲ期［H^R =1.744（95% CI：1.070，2.840）］、淋巴结转移［H^R =2.896（95% CI：1.114，7.531）］、miR-223 ≥ 4.76［HR =2.196（95% CI：1.085，4.445）］为结肠癌患者预后的危险因素（P <0.05），FBXW7 ≥ 1.23［H^R =0.388（95% CI：0.172，0.875）］为保护因素（P <0.05）。多因素Cox回归分析结果显示，侵犯浆膜［H^R =1.490（95% CI：1.154，1.924）］、病理分期Ⅲ期［H^R =1.979（95% CI：1.132，3.460）］、淋巴结转移［H^R =2.401（95% CI：1.015，5.677）］、miR-223≥ 4.76［H^R =2.140（95% CI：1.063，4.309）］为结肠癌患者预后的危险因素（P <0.05），FBXW7 ≥1.23［H^R =0.625（95% CI：0.475，0.823）］为保护因素（P <0.05）。结论 结肠癌组织miR-223高表达、FBXW7低表达与结肠癌患者病理分期、淋巴结转移及预后有关。

Abstract:

Objective To investigate the expression of microRNA-223 (miR-223) and F-Box and WD repeat domain containing 7 (FBXW7) in colon cancer (CC) tissues and the relationship with clinicopathological parameters and prognosis.Methods A total of 146 cases of CC tissues and paracancerous tissues surgically removed were collected, and miR-223 and FBXW7 mRNA expression in the tissues were detected by qRT-PCR. The presence of binding sites for miR-223 and FBXW7 was predicted through an online website to analyze the correlation between their expression and the relationship with clinicopathological parameters. The mean values of miR-223 and FBXW7 mRNA expression in CC tissues were divided into high and low expression groups, and the survival curves of CC patients with different miR-223 and FBXW7 mRNA expression were plotted using the K-M method. Multi-factor Cox regression was used to analyze the factors affecting the prognosis of CC patients.Results The expression of miR-223 in CC tissue was higher than that in paracancerous tissues, while the expression of FBXW7 mRNA was lower than that in paracancerous tissues (P < 0.05). The expression of miR-223 in CC tissues with TNM stage Ⅲ and lymph node metastasis was higher than that in stages I-Ⅱ and without lymph node metastasis, while the expression of FBXW7 mRNA was lower than that in stages Ⅰ-Ⅱ and without lymph node metastasis (P < 0.05). There was no statistically significant difference in the expression of miR-223 and FBXW7 mRNA in CC tissues of different genders, ages, tumor size, degree of differentiation, and presence or absence of invasion of the serosa (P > 0.05). Pearson correlation coefficient analysis showed a negative correlation between miR-223 and FBXW7 mRNA expression in CC tissue (r = -0.679, P < 0.05). During the follow-up period of 8 to 60 months, 35 cases died, the overall survival rate was 76.03% (111/146). The overall survival rate of the miR-223 high expression group was lower than that of the miR-223 low expression group (P < 0.05). The overall survival rate of the FBXW7 mRNA high expression group was higher than that of the FBXW7 mRNA low expression group (P < 0.05). Univariate Cox regression analysis showed that invasion of the serosa [H^R = 1.454 (95% CI: 1.086, 1.947)], TNM stage Ⅲ [H^R = 1.744 (95% CI: 1.070, 2.840) ], lymph node metastasis [H^R = 2.896 (95% CI: 1.114, 7.531)], miR-223 ≥ 4.76 [H^R= 2.196 (95% CI: 1.085, 4.445) ] were risk factors for the prognosis of CC patients, and FBXW7 mRNA ≥ 1.23 [H^R = 0.388 (95% CI: 0.172, 0.875) ] were protective factors (P < 0.05). The results of multivariate Cox regression analysis showed that invasion of the serosa [H^R = 1.490 (95% CI: 1.154, 1.924) ], TNM stage Ⅲ [H^R=1.979 (95% CI: 1.132, 3.460) ], lymph node metastasis [H^R = 2.401 (95% CI: 1.015, 5.677) ], miR-223 ≥ 4.76 [H^R = 2.140 (95% CI: 1.063, 4.309) ] were risk factors for the prognosis of CC patients, and FBXW7 mRNA ≥ 1.23 [H^R = 0.625 (95% CI: 0.475 0.823) ] were protective factors (P < 0.05).Conclusion High miR-223 expression and low FBXW7 expression in CC tissues were associated with TNM stage, lymph node metastasis, and prognosis in CC patients.