结直肠癌患者组蛋白H3K9me3和H3K27me3的表达及临床意义

Expressions and clinical significances of histone marks H3K9me3 and H3K27me3 in colorectal cancer patients

目的探讨组蛋白H3K9me3和H3K27me3在结直肠癌中的表达及临床意义。方法回顾性病例对照研究。回顾性分析2008年5月至2017年7月山西省肿瘤98例结直肠癌患者临床资料,其中未转移单纯手术组35例,同时性肝寡转移组29例,广泛转移组34例。选择2017年进行结肠镜检查的33例结直肠良性病变患者作为对照组。采用免疫组织化学方法检测各组H3K9me3及H3K27me3蛋白的表达;分析不同临床病理特征的结直肠癌患者H3K9me3及H3K27me3蛋白的表达情况;采用Kaplan-Meier法进行生存分析,并行log-rank检验。结果结直肠癌组H3K9me3蛋白阳性表达率为11.2%(11/98),低于对照组[60.6%(22/33)](χ^(2)=33.33,P<0.001);结直肠癌组H3K27me3蛋白阳性表达率为10.6%(13/98),低于对照组[97.0%(32/33)](χ^(2)=76.70,P<0.001)。对照组、未转移单纯手术组、同时性肝寡转移组和广泛转移组中,H3K9me3蛋白阳性表达率分别为60.6%(20/33)、17.1%(6/35)、10.3%(3/29)和5.9%(2/34),差异有统计学意义(χ^(2)=26.10,P<0.001);H3K27me3蛋白阳性表达率分别为97.0%(32/33)、14.3%(5/35)、20.7%(6/29)和5.9%(2/34),差异有统计学意义(χ^(2)=44.16,P<0.001)。淋巴结转移度≤0.2患者结直肠癌组织中H3K27me3阳性表达率高于淋巴结转移度>0.2的患者[22.4%(11/49)比4.2%(2/48),χ^(2)=6.98,P=0.008]。H3K9me3阳性和阴性结直肠癌患者中位总生存(OS)时间分别为77.0个月(95%CI:10.6~143.3个月)、34.0个月(95%CI:25.5~42.5个月),两组OS差异无统计学意义(P=0.078);H3K27me3阳性和阴性结直肠癌患者中位OS时间分别为39.0个月(95%CI:15.3~62.7个月)、34.0个月(95%CI:24.3~43.7个月),两组OS差异无统计学意义(P=0.524)。结论H3K9me3和H3K27me3在结直肠癌组织中的表达均低于结直肠良性病变组织,且随着肝转移、广泛转移的发生逐渐降低。H3K9me3和H3K27me3可能是潜在的抑癌因子。

Objective To investigate the expressions and clinical significances of histone marks H3K9me3 and H3K27me3 in colorectal cancer.Methods A retrospective case-control study was conducted.The clinical data of 98 patients with colorectal cancer in Shanxi Province Cancer Hospital from May 2008 to July 2017 were retrospectively analyzed,including 35 patients in the non-metastatic operation-only group,29 patients in the synchronous hepatic oligometastasis group and 34 patients in the extensive metastasis group,and 33 patients with benign colorectal lesions who underwent colonoscopy in 2017 were selected as the control group.Immunohistochemical assay was used to detect the expressions of H3K9me3 and H3K27me3 proteins in each group,and the expressions of H3K9me3 and H3K27me3 proteins in colorectal cancer patients with different clinicopathological features were analyzed.Kaplan-Meier method was used for survival analysis and log-rank test was performed.Results The positive expression rate of H3K9me3 protein in colorectal cancer group was 11.2%(11/98),which was lower than that in control group[60.6%(22/33)](χ^(2)=33.33,P<0.001);the positive expression rate of H3K27me3 protein in colorectal cancer group was 10.6%(13/98),which was lower than that in control group[97.0%(32/33)](χ^(2)=76.70,P<0.001).The positive expression rates of H3K9me3 protein were 60.6%(20/33),17.1%(6/35),10.3%(3/29)and 5.9%(2/34)in the control group,the non-metastatic operation-only group,the synchronous hepatic oligometastasis group and the extensive metastasis group,respectively,and the difference was statistically significant(χ^(2)=26.10,P<0.001);the positive expression rates of H3K27me3 protein were 97.0%(32/33),14.3%(5/35),20.7%(6/29)and 5.9%(2/34),respectively,and the difference was statistically significant(χ^(2)=44.16,P<0.001).The positive expression rate of H3K27me3 in colorectal cancer tissues of patients with lymph node metastasis degree≤0.2 was higher than that of patients with lymph node metastasis degree>0.2[22.4%(11/49)vs.4.2%(2/48),χ^(2)=6.98,P=0.008].The median overall survival(OS)time of H3K9me3 positive and negative colorectal cancer patients was 77.0 months(95%CI:10.6-143.3 months)and 34.0 months(95%CI:25.5-42.5 months),respectively,and there was no significant difference in OS between the two groups(P=0.078).The median OS time of H3K27me3 positive and negative colorectal cancer patients was 39.0 months(95%CI:15.3-62.7 months)and 34.0 months(95%CI:24.3-43.7 months),respectively,and there was no significant difference in OS between the two groups(P=0.524).Conclusions The expressions of H3K9me3 and H3K27me3 in colorectal cancer tissues are lower than those in colorectal benign lesions,and gradually decrease with occurrence of liver metastasis and extensive metastasis.H3K9me3 and H3K27me3 may be potential cancer suppressor factors.