DataSheet_1_Tumor-associated microbiome features of metastatic colorectal cancer and clinical implications.docx

BackgroundColon microbiome composition contributes to the pathogenesis of colorectal cancer (CRC) and prognosis. We analyzed 16S rRNA sequencing data from tumor samples of patients with metastatic CRC and determined the clinical implications.
Materials and methodsWe enrolled 133 patients with metastatic CRC at St. Vincent Hospital in Korea. The V3-V4 regions of the 16S rRNA gene from the tumor DNA were amplified, sequenced on an Illumina MiSeq, and analyzed using the DADA2 package.
ResultsAfter excluding samples that retained <5% of the total reads after merging, 120 samples were analyzed. The median age of patients was 63 years (range, 34–82 years), and 76 patients (63.3%) were male. The primary cancer sites were the right colon (27.5%), left colon (30.8%), and rectum (41.7%). All subjects received 5-fluouracil-based systemic chemotherapy. After removing genera with <1% of the total reads in each patient, 523 genera were identified. Rectal origin, high CEA level (≥10 ng/mL), and presence of lung metastasis showed higher richness. Survival analysis revealed that the presence of Prevotella (p = 0.052), Fusobacterium (p = 0.002), Selenomonas (p<0.001), Fretibacterium (p = 0.001), Porphyromonas (p = 0.007), Peptostreptococcus (p = 0.002), and Leptotrichia (p = 0.003) were associated with short overall survival (OS, <24 months), while the presence of Sphingomonas was associated with long OS (p = 0.070). From the multivariate analysis, the presence of Selenomonas (hazard ratio [HR], 6.35; 95% confidence interval [CI], 2.38–16.97; p<0.001) was associated with poor prognosis along with high CEA level.
ConclusionTumor microbiome features may be useful prognostic biomarkers for metastatic CRC.

研究背景：结肠微生物组组成与结直肠癌（colorectal cancer, CRC）的发病机制及预后密切相关。本研究针对转移性结直肠癌患者的肿瘤样本开展16S rRNA测序数据分析，以明确其临床意义。
材料与方法：本研究在韩国圣文森特医院纳入133例转移性结直肠癌患者。从肿瘤组织DNA中扩增16S rRNA基因的V3-V4可变区，采用Illumina MiSeq测序平台进行测序，并通过DADA2分析工具包完成数据分析。
研究结果：本研究剔除了序列合并后有效reads占总reads比例不足5%的样本，最终纳入120例样本进行分析。患者中位年龄为63岁（范围34~82岁），其中男性76例（占比63.3%）。原发肿瘤部位分布为：右半结肠27.5%、左半结肠30.8%、直肠41.7%。所有受试者均接受以5-氟尿嘧啶为基础的全身化疗。在剔除单个患者样本中相对丰度低于总reads 1%的菌属后，共鉴定出523个菌属。直肠来源肿瘤、癌胚抗原（CEA）水平升高（≥10 ng/mL）以及存在肺转移的患者，其菌群丰富度更高。生存分析结果显示，普雷沃菌属（Prevotella）（p=0.052）、梭杆菌属（Fusobacterium）（p=0.002）、硒单胞菌属（Selenomonas）（p<0.001）、Fretibacterium属（p=0.001）、卟啉单胞菌属（Porphyromonas）（p=0.007）、消化链球菌属（Peptostreptococcus）（p=0.002）以及纤毛菌属（Leptotrichia）（p=0.003）的存在与较短的总生存期（overall survival, OS，<24个月）相关；而鞘氨醇单胞菌属（Sphingomonas）的存在则与较长的总生存期相关（p=0.070）。多因素分析结果显示，硒单胞菌属的存在（风险比[HR]=6.35；95%置信区间[CI]=2.38~16.97；p<0.001）与高CEA水平均与不良预后相关。
研究结论：肿瘤微生物组特征可作为转移性结直肠癌的潜在预后生物标志物。