金鹏+盛剑秋+秦楠：基于肠道菌群标志物的大肠癌晚期腺瘤和癌症的诊断新模型
- ①纳入871名受试者（247 名结直肠癌（CRC）, 234名晚期腺瘤（AA）, 390名对照）粪便样本，进行全基因组关联研究；
- ②根据肠道微生物组的特征构建结直肠肿瘤分类器，并在3个独立队列的CRC、AA和对照组中进行验证；
- ③氨基酸代谢、膜转运和碳水化合物代谢，包含了最多与CRC的发展相关的进行性微生物群基因标记物；
- ④构建由4个效应指标组成的诊断模型，从对照组到晚期腺瘤，再到不同阶段的CRC，指数得分呈现持续增加趋势；
主编推荐语
肠道微生物群的改变与结直肠癌的发生密切相关，因此有必要寻找能够反映疾病动态变化的非侵入性微生物组生物标志物。Cell and Bioscience近期发表的来自中国人民解放军总医院金鹏+盛剑秋团队联合同济大学附属第十人民医院秦楠团队的研究，对来自不同阶段的结直肠晚期腺瘤和癌症患者以及对照组的样本进行了宏基因组分析，并确定了渐进式微生物群生物标志物。然后，根据这些标志物构建了一个诊断模型，并评估了其作为AA和CRC诊断工具的性能。结果表明，该新型诊断模型可以显著提高晚期腺瘤的诊断性能。
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A novel promising diagnosis model for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene biomarkers
基于进行性肠道微生物群基因生物标志物的结直肠癌晚期腺瘤和癌的诊断新模型
10.1186/s13578-022-00940-1
2022-12-26, Article
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Background: Colorectal cancer (CRC), a commonly diagnosed cancer often develops slowly from benign polyps called adenoma to carcinoma. Altered gut microbiota is implicated in colorectal carcinogenesis. It is warranted to find non-invasive progressive microbiota biomarkers that can reflect the dynamic changes of the disease. This study aimed to identify and evaluate potential progressive fecal microbiota gene markers for diagnosing advanced adenoma (AA) and CRC.
Results: Metagenome-wide association was performed on fecal samples from different cohorts of 871 subjects (247 CRC, 234 AA, and 390 controls). We characterized the gut microbiome, identified microbiota markers, and further constructed a colorectal neoplasms classifier in 99 CRC, 94 AA, and 62 controls, and validated the results in 185 CRC, 140 AA, and 291 controls from 3 independent cohorts. 21 species and 277 gene markers were identified whose abundance was significantly increased or decreased from normal to AA and CRC. The progressive gene markers were distributed in metabolic pathways including amino acid and sulfur metabolism. A diagnosis model consisting of four effect indexes was constructed based on the markers, the sensitivities of the Adenoma Effect Index 1 for AA, Adenoma Effect Index 2 for high-grade dysplasia (HGD) adenoma were 71.3% and 76.5%, the specificities were 90.5% and 90.3%, respectively. CRC Effect Index 1 for all stages of CRC and CRC Effect Index 2 for stage III–IV CRC to predict CRC yielded an area under the curve (AUC) of 0.839 (95% CI 0.804–0.873) and 0.857 (95% CI 0.793–0.921), respectively. Combining with fecal immunochemical test (FIT) significantly improved the sensitivity of CRC Effect Index 1 and CRC Effect Index 2 to 96.7% and 100%.
Conclusions: This study reports the successful diagnosis model establishment and cross-region validation for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene markers. The results suggested that the novel diagnosis model can significantly improve the diagnostic performance for advanced adenoma.
First Authors:
Junfeng Xu,Zhijun Zheng,Lang Yang
Correspondence Authors:
Nan Qin,Jianqiu Sheng,Peng Jin
All Authors:
Junfeng Xu,Zhijun Zheng,Lang Yang,Ruoran Li,Xianzong Ma,Jie Zhang,Fumei Yin,Lin Liu,Qian Xu,Qiujing Shen,Xiuping Shen,Chunyan Wu,Jing Liu,Nan Qin,Jianqiu Sheng,Peng Jin
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