A novel promising diagnosis model for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene biomarkers

Cell & Bioscience

Research

Jie Zhang¹  Jianqiu Sheng¹  Fumei Yin²  Xianzong Ma²  Ruoran Li²  Jing Liu³  Qiujing Shen³  Xiuping Shen³  Chunyan Wu³  Zhijun Zheng³  Lin Liu⁴  Qian Xu⁴  Nan Qin⁴  Junfeng Xu⁵  Peng Jin⁶  Lang Yang⁶ 

[1] Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, 100700, Beijing, China;Graduate School, Chinese PLA General Hospital, 100853, Beijing, China;Realbio Genomics Institute, 201114, Shanghai, China;Realbio Genomics Institute, 201114, Shanghai, China;Tenth People’s Hospital of Tongji University, 200072, Shanghai, China;Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, 100853, Beijing, China;Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, 100853, Beijing, China;Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, 100700, Beijing, China;

关键词: Colorectal cancer;    Advanced adenoma;    Metagenomic sequencing;    Progressive microbiota gene markers;    Diagnosis model;   

DOI  :  10.1186/s13578-022-00940-1

 received in 2022-10-13, accepted in 2022-12-07,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundColorectal 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.ResultsMetagenome-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%.ConclusionsThis 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.

【 授权许可】

CC BY   
© The Author(s) 2022

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