Integration of stool microbiota, proteome and amino acid profiles to discriminate patients with adenomas and colorectal cancer

整合粪便微生物群、蛋白质组和氨基酸谱来区分腺瘤和结直肠癌患者

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作者:Sofie Bosch, Animesh Acharjee, Mohammed Nabil Quraishi, Irene V Bijnsdorp, Patricia Rojas, Abdellatif Bakkali, Erwin Ew Jansen, Pieter Stokkers, Johan Kuijvenhoven, Thang V Pham, Andrew D Beggs, Connie R Jimenez, Eduard A Struys, Georgios V Gkoutos, Tim Gj de Meij, Nanne Kh de Boer

Background

Screening for colorectal cancer (CRC) reduces its mortality but has limited sensitivity and specificity. Aims We aimed to explore potential biomarker panels for CRC and adenoma detection and to gain insight into the interaction between gut microbiota and human metabolism in the presence of these lesions.

Conclusions

Integrating fecal microbiota, proteome and amino acids platforms provides for new biomarker panels that may improve noninvasive screening for adenomas and CRC, and may subsequently lead to lower incidence and mortality of colon cancer.

Methods

This multicenter case-control cohort was performed between February 2016 and November 2019. Consecutive patients ≥18 years with a scheduled colonoscopy were asked to participate and divided into three age, gender, body-mass index and smoking status-matched subgroups: CRC (n = 12), adenomas (n = 21) and controls (n = 20). Participants collected fecal samples prior to bowel preparation on which proteome (LC-MS/MS), microbiota (16S rRNA profiling) and amino acid (HPLC) composition were assessed. Best predictive markers were combined to create diagnostic biomarker panels. Pearson correlation-based analysis on selected markers was performed to create networks of all platforms.

Results

Combining omics platforms provided new panels which outperformed hemoglobin in this cohort, currently used for screening (AUC 0.98, 0.95 and 0.87 for CRC vs controls, adenoma vs controls and CRC vs adenoma, respectively). Integration of data sets revealed markers associated with increased blood excretion, stress- and inflammatory responses and pointed toward downregulation of epithelial integrity. Conclusions: Integrating fecal microbiota, proteome and amino acids platforms provides for new biomarker panels that may improve noninvasive screening for adenomas and CRC, and may subsequently lead to lower incidence and mortality of colon cancer.

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