HPV16阳性子宫颈鳞状细胞癌患者下生殖道菌群构成及特征  

Composition and characteristics of lower genital tract microbiota in HPV16-positive patients with cervical squamous cell carcinoma

作　　者：王国婧 李宁 李一帆 孙萍 朱宇 魏葆珺 崔巍 Wang Guojing;Li Ning;Li Yifan;Sun Ping;Zhu Yu;Wei Baojun;Cui Wei(Department of Clinical Laboratory,National Cancer Center,National Clinical Research Center for Cancer,Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Department of Gynecological Oncology,National Cancer Center,National Clinical Research Center for Cancer,Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Department of Cancer Prevention,National Cancer Center,National Clinical Research Center for Cancer,Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China)

机构地区：[1]国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院、北京协和医学院肿瘤医院检验科,北京100021 [2]国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院、北京协和医学院肿瘤医院妇瘤科,北京100021 [3]国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院、北京协和医学院肿瘤医院防癌科,北京100021

出　　处：《肿瘤研究与临床》2024年第8期576-582,共7页Cancer Research and Clinic

基　　金：中国癌症基金会北京希望马拉松专项基金(LC2018B16)。

摘　　要：目的探讨人乳头瘤病毒(HPV)16亚型感染的子宫颈鳞状细胞癌患者下生殖道菌群的分布及特征。方法前瞻性横断面研究。选取2019年8月至2020年6月就诊于中国医学科学院肿瘤医院的6例HPV16单一型别阳性子宫颈鳞状细胞癌患者(子宫颈癌组),选取同期体检人群中液基薄层细胞学检查未见异常且HPV阴性6名健康女性为健康对照组。患者抗肿瘤治疗前、健康对照者体检时用无菌棉拭子采集子宫颈后穹窿处分泌物,采用高通量测序技术扩增细菌16S rRNA基因V1-V2高变区,分析菌群分布及特征。结果子宫颈癌组和健康对照组年龄分别为(51±8)岁、(48±3)岁,差异无统计学意义(t=0.63,P=0.540),两组均有孕产史,无吸烟史。α多样性分析结果显示,与健康对照组比较,子宫颈癌组sobs指数(t=3.25,P=0.009)及chao指数(t=2.91,P=0.016)均高,差异均有统计学意义;子宫颈癌组shannon指数高(t=2.07,P=0.065),simpson指数低(t=1.74,P=0.113),但差异均无统计学意义。采用基于bray-curtis距离的主坐标分析(PCoA)进行数据降维分析显示,子宫颈癌组与健康对照组间β多样性差异具有统计学意义(R 2=0.154,P=0.018)。门水平上,与健康对照组相比,子宫颈癌组厚壁菌门占比低(30.21%比68.28%),拟杆菌门占比略低(6.87%比8.11%),而放线菌门(26.91%比14.42%)及变形菌门(27.33%比0.67%)占比高。属水平上,与健康对照组相比,子宫颈癌组乳杆菌属及棒状菌属占比低,失去优势菌群,而红球菌属、克雷伯菌属、气球菌属等占比明显高,且子宫颈癌组菌群种类较健康对照组多。线性判别分析(LDA)显示,属水平上,红球菌属(LDA=5.04)、克雷伯菌属(LDA=4.71)、肠杆菌属(LDA=4.29)、罗尔斯通菌属(LDA=4.28)、苍白杆菌属(LDA=4.23)、韦荣球菌属(LDA=4.14)为子宫颈癌组特征菌群;门水平上,健康对照组厚壁菌门(LDA=5.23)可为标志性物种;种水平上,子宫颈癌组红球菌(P=0.025)、罗尔斯通菌(P=0.ObjectiveTo explore the distribution and characteristics of microbiota in the lower reproductive tract of patients with cervical squamous cell carcinoma infected by human papilloma virus(HPV)16 subtype.MethodsA prospective,cross-sectional study was conducted.A total of 6 patients with HPV16 single subtype positive cervical squamous cell carcinoma admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from August 2019 to June 2020 were selected as cervical carcinoma group,and 6 healthy women who did not indicate abnormalities in thin-based layer cytology test(TCT)during the same period among the physical examination population and had HPV negative test result were selected as the healthy control group.A sterile cotton swab was used to collect secretions from the posterior cervical fornix in patients before antitumor treatment and healthy controls during physical examination.The high variable region of the 16S rRNA gene V1-V2 of the bacteria was amplified by using next generation sequencing(NGS),and then the distribution and characteristics of the bacteria were analyzed.ResultsThe age of cervical cancer group and the healthy control group was(51±8)years and(48±3)years,respectively,and the difference in age between the both groups was statistically significant(t=0.63,P=0.540).The patients of both groups had reproductive history and no smoking experience.Alpha diversity analysis showed that compared with the healthy control group,the sobs(t=3.25,P=0.009)and chao(t=2.91,P=0.016)indexes were higher in cervical cancer group,and the differences were statistically significant.The shannon index was higher(t=2.07,P=0.065)and simpson index was lower(t=1.74,P=0.113)in cervical cancer group,while the difference was not statistically different.Data dimensionality reduction analysis in principal coordinate analysis(PCoA)based on bray-curtis distance showed that the difference in Beta diversity between the healthy control group and cervical cancer group was statistically significant(R 2=0.154,P=0.018).At the phy

关 键 词：宫颈肿瘤 癌 鳞状细胞 人乳头瘤病毒16 下生殖道 微生物群落 高通量测序 

分 类 号：R737.33[医药卫生—肿瘤]