Cai Ping, Yang Qingzhen, Lu Jiaqi, Dai Xiaoyu, Xiong Jinbo
Ningbo No.2 Hospital, Ningbo, China.
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
mSystems. 2025 Mar 18;10(3):e0004325. doi: 10.1128/msystems.00043-25. Epub 2025 Feb 27.
The incidence of colorectal cancer (CRC) has been increasing in recent decades. Current methods for CRC screening have their own drawbacks, thus there is an urgent need to identify the key microbes that drive the development of CRC for wider application in the early detection and prevention of CRC. To address this issue, we performed fecal microbiome analysis by high-throughput sequencing of 16S rRNA gene combined with blood biochemical indicators in patients with CRC stages I, II, III, and IV, healthy people, and patients with polyps. Fecal microbiota of patients with CRC was disturbed, as evidenced by significantly reduced α-diversity in patients with CRC stage IV and markedly different β-diversity. The random forest model identified the top 25 genera from 174 training data, resulting in a diagnostic accuracy of 87.95%. Further, by combining with differential genera analysis, we screened out 11 biomarkers that significantly changed in different groups. , , , , , and associated with the development of CRC were significantly enriched, while , , , and associated with the remission of CRC were significantly suppressed in patients with CRC. Importantly, carcinoembryonic antigen (CEA) was significantly correlated with these 11 microbial biomarkers, and carbohydrate antigen 19-9 (CA 19-9) was markedly correlated with . Notably, co-occurrence network analysis at the genus level exhibited that the microbial co-occurrence network of CRC IV was the most complex and stable. These results suggested that CEA, CA 19-9 and 11 microbial biomarkers may be co-biomarkers for the disease occurrence and development, and non-invasive diagnosis of CRC.
Identifying the key microbes that drive the development of colorectal cancer (CRC) has been important in this field. We delved into the research on the association between CRC and fecal microbiota in this study, providing a detailed analysis of the characteristics of fecal microbiota during the transition from normal intestine to polyps to cancer. Fecal bacterial biomarkers and blood biochemical indicators may be co-biomarkers in the development of CRC.
近几十年来，结直肠癌（CRC）的发病率一直在上升。目前的CRC筛查方法都有其自身的缺点，因此迫切需要确定驱动CRC发展的关键微生物，以便在CRC的早期检测和预防中更广泛地应用。为了解决这个问题，我们通过对I、II、III和IV期CRC患者、健康人和息肉患者的16S rRNA基因进行高通量测序，并结合血液生化指标，进行了粪便微生物组分析。CRC患者的粪便微生物群受到干扰，IV期CRC患者的α多样性显著降低以及β多样性明显不同证明了这一点。随机森林模型从174个训练数据中识别出前25个属，诊断准确率为87.95%。此外，通过结合差异属分析，我们筛选出了11个在不同组中显著变化的生物标志物。与CRC发展相关的[具体生物标志物1]、[具体生物标志物2]、[具体生物标志物3]、[具体生物标志物4]、[具体生物标志物5]和[具体生物标志物6]在CRC患者中显著富集，而与CRC缓解相关的[具体生物标志物7]、[具体生物标志物8]、[具体生物标志物9]、[具体生物标志物10]和[具体生物标志物11]在CRC患者中显著受到抑制。重要的是，癌胚抗原（CEA）与这11种微生物生物标志物显著相关，碳水化合物抗原19-9（CA 19-9）与[具体生物标志物12]显著相关。值得注意的是，属水平的共现网络分析表明，IV期CRC的微生物共现网络最为复杂和稳定。这些结果表明，CEA、CA 19-9和11种微生物生物标志物可能是该疾病发生发展和CRC非侵入性诊断的联合生物标志物。
确定驱动结直肠癌（CRC）发展的关键微生物在该领域一直很重要。我们在本研究中深入探讨了CRC与粪便微生物群之间的关联，详细分析了从正常肠道到息肉再到癌症转变过程中粪便微生物群的特征。粪便细菌生物标志物和血液生化指标可能是CRC发展中的联合生物标志物。
