A New Biomarker of Fecal Bacteria for Non-Invasive Diagnosis of Colorectal Cancer

Abstract

BackgroundThe intestinal flora is correlated with the occurrence of colorectal cancer. We evaluate a new predictive model for the non-invasive diagnosis of colorectal cancer based on intestinal flora to verify the clinical application prospects of the intestinal flora as a new biomarker in non-invasive screening of colorectal cancer.MethodsSubjects from two independent Asian cohorts (cohort I, consisting of 206 colorectal cancer and 112 healthy subjects; cohort II, consisting of 67 colorectal cancer and 54 healthy subjects) were included. A probe-based duplex quantitative PCR (qPCR) determination was established for the quantitative determination of candidate bacterial markers.ResultsWe screened through the gutMEGA database to identify potential non-invasive biomarkers for colorectal cancer, including Prevotella copri (Pc), Gemella morbillorum (Gm), Parvimonas micra (Pm), Cetobacterium somerae (Cs), and Pasteurella stomatis (Ps). A predictive model with good sensitivity and specificity was established as a new diagnostic tool for colorectal cancer. Under the best cutoff value that maximizes the sum of sensitivity and specificity, Gm and Pm had better specificity and sensitivity than other target bacteria. The combined detection model of five kinds of bacteria showed better diagnostic ability than Gm or Pm alone (AUC = 0.861, P < 0.001). These findings were further confirmed in the independent cohort II. Particularly, the combination of bacterial markers and fecal immunochemical test (FIT) improved the diagnostic ability of the five bacteria (sensitivity 67.96%, specificity 89.29%) for patients with colorectal cancer.ConclusionFecal-based colorectal cancer-related bacteria can be used as new non-invasive diagnostic biomarkers of colorectal cancer. Simultaneously, the molecular biomarkers in fecal samples are similar to FIT, have the applicability in combination with other detection methods, which is expected to improve the sensitivity of diagnosis for colorectal cancer, and have a promising prospect of clinical application.

A systematic review of microbiome-derived biomarkers for early colorectal cancer detection

“…For microbiome-derived biomarkers based on bacteria for the detection of early CRC, 26 articles were found and two articles were found investigating the co-metabolome solely as a biomarker. Seventeen of the studies were conducted in East Asia [ 19 , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] ], one in South Asia [43] , eight in Europe [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] and two in North America [ 52 , 53 ]. The number of inclusions of these studies ranged between 2 and 462 for CRC, 18 and 665 for adenoma and/or polyp and 24 and 788 for healthy controls.…”

“…The number of inclusions of these studies ranged between 2 and 462 for CRC, 18 and 665 for adenoma and/or polyp and 24 and 788 for healthy controls. Regarding the stage used in the articles for early CRC detection, five studies were based on stage I or II [ 29 , 30 , 37 , 40 , 50 ] and two used stage 0 [ 19 , 38 ]. The other studies investigated a precursor lesion of CRC, either advanced adenomas or polyps (AP) [ 28 , [31] , [32] , [33] , [34] , [35] , 39 , 41 , [44] , [45] , [46] , [47] , [48] , [49] , [51] , [52] , [53] ].…”

GutMeta: online microbiome analysis and interactive visualization with build-in curated human gut microbiome database

“…In early 2001, Ramon et al reported the association of G. morbillorum and colon cancer [35]. A recent work of Yao et al identified G. morbillorum as one of the non-invasive biomarkers of CRC from gutMEGA database [36]. E. hallii is a common gut microbe with probiotic properties regard to intestinal metabolic balance as contributing to propionate formation [37].…”

Development of the First Tractable Genetic System for Parvimonas micra, a Ubiquitous Pathobiont in Human Dysbiotic Disease

“…It is also one of the most abundant species in numerous types of systemic abscesses, and it exhibits a surprisingly strong association with a variety of malignant tumors ( 4 – 7 ). In fact, P. micra has even been proposed as a discriminating biomarker for colorectal cancer, gastric cancer, and oral cancer ( 4 , 8 , 9 ). In the oral cavity, P. micra exists as a low-abundance species during oral health but is highly enriched in periodontitis lesions and infected root canals and is especially prevalent in polymicrobial odontogenic abscesses ( 10 – 15 ).…”