基于肠道菌群结构特征研究胰腺癌不同中医证型与预后的相关性

Correlation between Different TCM Syndrome Types of Pancreatic Cancer and their Prognosis Based on Structural Characteristics of Intestinal Flora

目的研究胰腺癌不同中医证型肠道菌群结构特征与其总生存期的相关性。方法收集2018年1月1日—2018年9月30日在浙江省肿瘤医院腹部肿瘤放疗科及腹部肿瘤内科收治的胰腺癌患者28例,根据中医证型的不同,分为气血瘀滞组9例,脾虚湿热组9例,湿热内蕴组10例。另设浙江中医药大学研究生正常健康人群8名作为健康对照组。采集研究对象的粪便标本,进行16S rDNA测序,检测各组间肠道菌群的多样性和丰度,通过组间差异分析明确差异菌属,用Log rank法比较胰腺癌三种中医证型的总生存期差异。结果显著性差异分析结果显示,胰腺癌不同中医证型间具有明显差异(P<0.05)的菌属包括产碱杆菌属(Alcaligenes)、奇异菌属(Atopobium)和弯曲杆菌属(Campylobacter)等在内的16个菌属;组间差异菌属中,纤毛菌属(Leptotrichia)、奇异菌属(Atopobium)、颗粒链菌属(Granulicatella)、链球菌属(Streptococcus)及弯曲杆菌属(Campylobacter)在脾虚湿热组丰度均值最高,湿热内蕴组最低(除弯曲杆菌属外);生存分析显示,气血瘀滞组中位生存时间12个月,脾虚湿热组为8个月,湿热内蕴组为18个月,三组的总生存期差异有统计学意义(P=0.029)。结论脾虚湿热组中与胰腺癌发生发展可能正相关的菌属丰度最高,其预后最差;而湿热内蕴组与胰腺癌发生发展可能正相关的菌属丰度则最低,其预后最好。

Objective To investigate the correlation between the structural characteristics of intestinal flora of different TCM syndromes of pancreatic cancer and the overall survival time.Methods Twenty-eight patients with pancreatic cancer admitted to the Department of Abdominal Tumor Radiotherapy and Department of Abdominal Tumor Internal Medicine of Zhejiang Cancer Hospital,from January 1,2018 to September 30,2018,were recruited.According to different TCM syndromes,patients were divided into qi stagnation and blood stasis group(9 cases),spleen deficiency and dampness-heat group(9 cases)and internal retention of damp-heat group(10 cases).Eight healthy postgraduates from Zhejiang Chinese Medical University were recruited as healthy control group.Stool samples were collected and 16S rDNA sequencing was carried out to detect the diversity and abundance of intestinal flora among the groups.By analyzing the differences between the groups,the differential bacteria genera were identified.The overall survival differences of three TCM syndromes of pancreatic cancer were compared with log rank method.Results The results showed that there were significant differences among different TCM syndromes of pancreatic cancer among 16 genera including Alcaligenes,Atopobium and Campylobacter(P<0.05).Leptotrichia,Atopobium,Granulicatella,Streptococcus and Campylobacter had the highest abundance in the spleen deficiency and dampness-heat group,and the lowest in the internal retention of damp-heat group(except Campylobacter).Survival analysis showed that the median survival time of the qi stagnation and blood stasis group was 12 months,8 months for spleen deficiency and dampness-heat group,and 18 months for internal retention of damp-heat group.The difference of overall survival time in three groups was significant(P=0.029).Conclusion In the spleen deficiency and dampness-heat group,abundance of bacteria that may be positively related to the occurrence and development of pancreatic cancer was the highest,and the prognosis is the worst.However,in the internal retention of damp-heat group,abundance of bacteria that may be positively related to the occurrence and development of the disease is the lowest,and the prognosis is the best.