B细胞异位基因2在胰腺癌组织中的表达及临床意义

Expression and clinical significance of B cell ectopic gene 2 in pancreatic cancer tissue

目的检测B细胞异位基因2(BTG2)在胰腺癌组织的表达情况, 分析其与胰腺癌临床病理特征和预后的关系。方法收集2015年6月至2020年12月间湖北医药学院附属国药东风总医院病理科石蜡封存的46例胰腺癌组织、对应的癌旁组织及肝胆胰外科9例行手术切除的新鲜胰腺癌组织、对应的癌旁组织, 采用免疫组织化学染色法检测46例胰腺癌组织及癌旁组织BTG2蛋白表达情况, 根据BTG2表达水平将其分为BTG2高表达组和低表达组。采用RT-PCR法检测9例胰腺癌组织、癌旁组织BTG2基因表达量。分析BTG2蛋白表达水平与患者临床病理特征的相关性, 采用Kaplan-Meier法绘制生存时间图及死亡风险曲线图, 应用单因素和多因素Cox回归模型分析影响胰腺癌患者预后的因素。结果 46例胰腺癌组织中BTG2高表达29例(63.04%), 对应癌旁组织中BTG2高表达38例(82.61%), 癌旁组织BTG2高表达率显著高于癌组织;9例胰腺癌组织中3例为高分化, 6例为中低分化, 高分化胰腺癌组织BTG2表达量显著高于中低分化癌组织(0.66±0.07比0.24±0.18), 癌旁组织表达量显著高于癌组织(1.00±0.00比0.38±0.30), 差异均有统计学意义(P值均<0.001)。胰腺癌BTG2低表达与肿瘤分化程度低、有血管侵犯相关(P值均<0.05), 而与肿瘤位置、大小、淋巴结转移、CA19-9水平、术后肝转移无关。BTG2高表达组中位生存期显著长于BTG2低表达组(525 d比266 d, P<0.001);生存≥300 d患者BTG2高表达组生存时间显著长于BTG2低表达组[(616±135)d比(426±113)d], 差异有统计学意义(P<0.001), 而生存<300 d患者BTG2高表达组与低表达组生存时间差异无统计学意义。单因素分析结果显示, 肿瘤分化程度、血管侵犯、BTG2表达、CA19-9水平、术后肝转移均与胰腺癌患者预后有关;多因素分析结果显示, BTG2表达水平(HR=2.572, 95%CI1.140~5.802, P=0.023)、血管侵犯(HR=0.203, 95%CI0.072~0.572, P=0.003)及术后肝转移(HR=0.240, 95%CI0.102~0.564, P<0.001)为影响胰腺癌患者预后的独立危险因素。结论胰腺癌组织BTG2表达量显著低于癌旁组织, 其低表达与胰腺癌侵袭性强、分化程度低及预后差相关。BTG2对胰腺癌患者预后的影响主要在远期。

Objective To investigate the expression of the B cell ectopic gene 2(BTG2)in the pancreatic cancer tissue and analyze its relationship with the clinicopathological features and prognosis.Methods 46 pairs of pancreatic cancer tissues and corresponding adjacent tissues kept in paraffin in the pathology department,and 9 fresh pancreatic cancer tissues and corresponding adjacent tissues resected by surgery in Department of Pancreatic Surgery of Sinopharm Dongfeng General Hospital from June 2015 to December 2020 were collected.BTG2 gene expression in 46 pairs of pancreatic cancer tissues and corresponding adjacent tissues were detected by immunohistochemical staining,and high and low BTG2 expression groups were divided.BTG2 gene expression in 9 fresh pancreatic cancer tissues and corresponding adjacent tissues were detected by RT-PCR.The correlation between BTG2 protein expression level and clinicopathological features was analyzed.Furthermore,the survival curve and death risk curve were drawn using the Kaplan-Meier method,and the Cox regression hazards model was applied for the univariate and multivariate analysis of the factors affecting the prognosis of pancreatic cancer.Results 29 of 46(63.04%)pancreatic cancer tissues had high BTG2 expression,and 38(82.61%)of corresponding adjacent tissues had high BTG2 expression;and BTG2 high expression rate of adjacent tissues was significantly higher than that of cancer tissues.Three out of 9 pancreatic cancer tissues were highly differentiated,and six cases had medium-and low differentiation.The BTG2 expression of highly differentiated pancreatic carcinoma was significantly higher than that of moderately and poorly differentiated carcinoma tissues(0.66±0.07 vs 0.24±0.18);the expression level of adjacent tissues was significantly higher than that of cancer tissues(1.00±0.00 vs 0.38±0.30),and all differences were statistically significant(all P values<0.001).Low BTG2 expression in pancreatic cancer was associated with low tumor differentiation and vascular invasion(all P values<0.05),but was not correlated with tumor location,volume,lymph node metastasis,CA19-9 level and postoperative liver metastasis.The median survival of high BTG2 expression group was significantly longer than that of low BTG2 expression group(525 d vs 266 d,P<0.001).Among patients with survival time≥300 d,the survival time was significantly higher in the high BTG2 expression group than in the BTG2 low expression group(616±135d vs 426±113 d),and the difference was statistically significant(P<0.001).Among patients with survival time<300 d,there was no significant difference between BTG2 high and low expression group.The results of the univariate analysis showed that tumor differentiation degree,vascular invasion,BTG2 expression,CA19-9 levels,and postoperative liver metastasis were all associated with the prognosis of pancreatic cancer.The results of the multivariate analysis showed that BTG2 expression level(HR=2.572,95%CI1.140-5.802,P=0.023),vascular invasion(HR=0.023,95%CI0.072-0.572,P=0.003)and postoperative liver metastasis(HR=0.240,95%CI0.102-0.564,P<0.001)were independent risk factors affecting the prognosis of patients with pancreatic cancer.Conclusions BTG2 expression in pancreatic cancer tissues was significantly lower than that in adjacent tissues,and its low expression was associated with strong aggressiveness,low differentiation degree and poor prognosis of pancreatic cancer.The effect of BTG2 on the prognosis in pancreatic cancer patients was mainly in the long term.