B细胞急性淋巴瘤9L蛋白在结肠癌中的表达和临床意义及其与预后的关系

Expression and clinical significance of B-cell CLL/lymphoma 9-like(BCL9L)protein in colon cancer and its relationship with prognosis

目的探讨B细胞急性淋巴瘤9L(BCL9L)蛋白在结肠癌中的表达和临床意义及其对患者术后预后的影响。方法选取2012年1月—2014年1月行手术治疗的68例结肠癌患者。对患者结肠癌组织和癌旁正常组织标本行免疫组织化学染色、蛋白质印迹法检测BCL9L蛋白表达、实时荧光定量(qRT)-PCR检测BCL 9 L mRNA。采用多因素Cox回归分析影响结肠癌手术预后的因素,Kaplan-Meier法绘制生存曲线,Spearman检验分析BCL9L蛋白与肿瘤复发转移的相关性。结果结肠癌组织BCL9L蛋白表达评分显著低于癌旁正常组织(P<0.001)。与BCL9L蛋白高表达患者相比,低表达患者的淋巴结转移、TNM分期为晚期(Ⅲ或Ⅳ期),以及切缘肿瘤细胞阳性比例更高(P值均<0.05)。患者术后随访8~59个月(中位随访时间38个月),36例肿瘤无复发,32例复发;复发的患者中30例死亡。多因素Cox回归分析显示,淋巴结转移、临床分期为晚期、切缘肿瘤细胞阳性和BCL9L蛋白低表达均是结肠癌术后患者3年总体生存率的独立危险因素(P值均<0.05)。术后3年总体复发率和生存率分别为52.94%和55.88%,而BCL9L蛋白低表达和高表达结肠癌患者术后3年的生存率分别为38.10%和84.62%。生存曲线显示,BCL9L蛋白高表达的结肠癌患者总体生存率显著高于低表达患者(log rank P=0.0058)。Spearman相关性分析结果显示,BCL9L蛋白低表达与结肠癌术后肿瘤复发和死亡明显相关(r=0.862、0.640,P值均<0.05)。结论BCL9L蛋白在结肠癌中的表达水平与术后肿瘤复发相关,可作为结肠癌患者肿瘤复发与转移的预测指标。

Objective To investigate the expression and clinical significance of B-cell CLL/lymphoma 9-like(BCL9L)protein in colon cancer.Methods A total of 68 patients with colon cancer who underwent surgical treatment between January 2012 and January 2014 were enrolled in this study.Immunohistochemical staining and Western Blot were performed on colon cancer tissues and adjacent normal tissue specimens of patients to detect BCL9L protein expression,and real-time quantitative polymerase chain reaction(qRT-PCR)was performed to detect BCL9L mRNA expression.Multivariate Cox regression analyses were used to detect the factors affecting the prognosis of colon cancer after surgery.Survival curve was drawn by Kaplan-Meier method.The correlation between BCL9L protein and tumor recurrence and metastasis was assessed by Spearman test.Results The expression of BCL9L protein in colon cancer tissues was significantly lower than that in adjacent tissues(P<0.001).Compared with patients with high BCL9L protein expression,patients with low BCL9L protein expression had higher proportion of lymph node metastasis,advanced TNM stage,and positive surgical margin(all P<0.05).The median follow-up time was 38 months(range,8-59 months).And 36 patients had no tumor recurrence in and 32 patients had recurrence;and 30 patients who had relapse died.Multivariate analyses showed that lymph node metastasis,clinical staging,positive surgical margin,and BCL9L protein expression level were key factors affecting 3-year survival rate of colon cancer(all P<0.05).The overall 3-year postoperative recurrence and survival rates were 52.94%and 55.88%,respectively.The 3-year survival rate in patients with low-and high-BCL9L protein expression was 38.10%and 84.62%,respectively.Survival curve showed that the overall survival rate of colon cancer patients with high BCL9L protein expression was significantly higher than that of patients with low BCL9L protein expression(log rank P=0.0058).Spearman correlation analysis showed that low expression of BCL9L protein was significantly correlated with tumor recurrence and mortality in patients with colon cancer after surgery(r=0.862,0.640,both P<0.05).Conclusion The expression level of BCL9L protein in colon cancer is related to postoperative tumor recurrence.BCL9L protein can be used as a predictive indicator of tumor recurrence and metastasis in patients with colon cancer.