PO.TB10.14 · 肿瘤生物学
高体质指数患者的肿瘤微生物谱与CpG岛甲基化表型高或早发性结直肠癌相似
Patients with high body mass index share tumor microbial profiles with CpG island methylator phenotype-high or early-onset colorectal cancers
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景 肿瘤微生物群通过影响肿瘤发生和进展在结直肠癌(CRC)中发挥重要作用。我们此前的研究证实,在早发性CRC(EOCRC,年龄<50岁)中,高体质指数(高BMI,BMI≥27.5 kg/m^2)与CpG岛甲基化表型高(CIMP-high)之间存在显著关联。本研究探讨肿瘤微生物群是否可能在CRC中介导这一关联。
材料与方法 我们分别从台湾大学医院生物样本库纳入了140例CRC患者和30例息肉患者。采集了每个肿瘤或息肉中的肿瘤部分及邻近正常部分。扩增细菌16S核糖体RNA基因的V3-V4区,然后在MiSeq系统上对扩增子进行测序。同时记录了患者的临床病理特征。CIMP状态通过一个5基因panel(p16、MINT1、MINT2、MINT31和MLH1)和MethyLight检测来定义。对肿瘤微生物群进行了多样性分析和LefSe(线性判别分析效应量),并将结果在各亚组之间进行比较。
结果 总计121例CRC肿瘤(CRC-T)、115例邻近正常组织(CRC-N)和26例息肉(polyp-T和polyp-N)通过了质量控制(测序深度>5000 reads)。微生物群alpha多样性在CRC中显著低于息肉(p = 1.3 x 10^-11)。高BMI的CRC患者的微生物群alpha多样性也低于低BMI患者(p = 0.042)。LefSe分析揭示了在各亚组(包括EOCRC、高BMI和CIMP-high)中富集的特定微生物群。维恩图揭示了高BMI亚组与CIMP-high或EOCRC亚组之间存在多个重叠的细菌分类单元。
结论 我们发现高BMI的CRC中微生物群的多样性显著低于低BMI的CRC,并鉴定出在高BMI与CIMP-high或EOCRC肿瘤之间共享的特定细菌分类单元。这些细菌分类单元的临床应用有待进一步探索。
查看英文原文 English abstract
Background Tumor microbiota plays a significant role in colorectal cancer (CRC) by influencing tumor development and progression. Our previous study demonstrated a significant association between high body mass index (high BMI, BMI ≥ 27.5 kg/m 2 ) and CpG island methylator phenotype-high (CIMP-high) in early-onset CRC (EOCRC, age < 50y). The present study investigates whether tumor microbiota may mediate this association in CRC.
Materials and methods We enrolled 140 patients with CRC and 30 patients with polyps from the biobank of National Taiwan University Hospital, respectively. The tumor and adjacent normal part in each tumor or polyp were collected. V3-V4 regions of bacterial 16S ribosomal RNA gene were amplified and then amplicons were sequenced on the MiSeq system. Patients' clinicopathological characteristics were also recorded. CIMP status was defined by using a 5-gene panel ( p16, MINT1, MINT2, MINT31 and MLH1 ) and MethyLight assay. Analysis of diversity and LefSe (Linear discriminant analysis Effect Size) of tumor microbiota were performed and the results were compared between each subgroup.
Results In total, 121 CRC tumors (CRC-T), 115 adjacent normal (CRC-N) and 26 polyps (polyp-T and polyp-N) passed the quality control (sequencing depth > 5000 reads). Microbiota alpha diversity is significantly lower in CRC compared to that in polyps ( p = 1.3 x 10 -11 ). Microbiota alpha diversity is also reduced in CRC patients with high BMI compared to those with low BMI ( p = 0.042). LefSe analyses revealed specific microbiota enriched in each subgroup, including EOCRC, high BMI, and CIMP-high. The Venn diagram revealed multiple overlapping bacteria taxa between the high BMI and the CIMP-high or EOCRC subgroups.
Conclusion We found the diversity of microbiota in CRC with high BMI is significantly lower than that in CRC with low BMI and identified specific bacteria taxa shared between high BMI and CIMP-high or EOCRC tumors. The clinical applications of these bacterial taxa warrant further exploration.
利益披露 Disclosure
K. Chen, None..
J. Hsu, None..
Y. Su, None..
S. Lin, None..
B. Lin, None..
K. Tsai, None..
L. Tseng, None..
J. Tsai, None..
C. Tsai, None..
T. Liu, None.