Reduction of faecal immunochemical test false‐positive results using a signature based on faecal bacterial markers

Abstract

Background: Colorectal cancer is the second commonest cause of cancer mortality.Some countries are implementing colorectal cancer screening to detect lesions at an early stage using non-invasive tools like the faecal immunochemical test. Despite affordability, this test shows a low sensitivity for precancerous lesions and a low positive predictive value for colorectal cancer, resulting in a high false-positive rate.Aim: To develop a new, non-invasive colorectal cancer screening tool based on bacterial faecal biomarkers, which in combination with the faecal immunochemical test, could allow a reduction in the false-positive rate. This tool is called risk assessment of intestinal disease for colorectal cancer (RAID-CRC). Methods:We performed both the faecal immunochemical test and the bacterial markers analysis (RAID-CRC test) in stool samples from individuals with normal colonoscopy (167), non-advanced adenomas (88), advanced adenomas (30) and colorectal cancer (48). All the participants showed colorectal cancer-associated symptoms.Results: Performance of the faecal immunochemical test for advanced neoplasia (ie advanced adenoma and colorectal cancer) was determined by using the cut-off value established in Catalonia (20 µg haemoglobin/g of faeces) for a population-based screening approach. Sensitivity and specificity values of 83% and 80%, respectively, and positive and negative predictive values of 56% and 94%, respectively, were obtained. When both the immunological and the biological analysis were combined, the corresponding values were 80% and 90% for sensitivity and specificity, respectively, and 70% and 94% for positive and negative predictive values, respectively, resulting in a 50% reduction of the false-positive rate.Conclusions: RAID-CRC test allows a substantial reduction in the faecal immunochemical test false-positive results (50%) in a symptomatic population. Further validation is indicated in a colorectal cancer-screening scenario. | 1411MALAGÓN et AL.

Human Gut Microbiome-Based Knowledgebase as a Biomarker Screening Tool to Improve the Predicted Probability for Colorectal Cancer

“…Both Rb and EUB are butyrate-producing Firmicutes and metabolize dietary fibers to provide energy sources and achieve anti-inflammatory effects (Paramsothy et al, 2019). Their capabilities as a non-invasive tool were additionally evaluated but not included in the final model (Malagón et al, 2019). More recently, the utility of other widely recognized markers, including Fn, colibactin-producing E. coli and ETBF, in diagnosis of CRC has been systematically analyzed (Chung et al, 2018;Malagón et al, 2019;Wu et al, 2019;Pleguezuelos-Manzano et al, 2020).…”

“…Their capabilities as a non-invasive tool were additionally evaluated but not included in the final model (Malagón et al, 2019). More recently, the utility of other widely recognized markers, including Fn, colibactin-producing E. coli and ETBF, in diagnosis of CRC has been systematically analyzed (Chung et al, 2018;Malagón et al, 2019;Wu et al, 2019;Pleguezuelos-Manzano et al, 2020). However, several NA, non-available; Meta, meta-analysis; Gemella morbillorum (Gm); Bacteroides fragilis (Bf); pks + clbA + Escherichia coli (pks); Clostridium symbiosum (Cs); Atopobium parvulum (Ap); Granulicatella (Gl); Bacteroides (Bd); afaC-positive E. coli (afaC).…”

“…ETBF was shown to be increased in tumor tissues and form a biofilm in the gut. However, this pathogenic bacterium displayed no significant differences in abundance in patient fecal samples and was not detectable using qPCR targeting the toxin-producing gene, making it difficult to discriminate between patients and healthy controls (Zackular et al, 2014;Kosumi et al, 2018;Sze and Schloss, 2018;Malagón et al, 2019;Saffarian et al, 2019). Finally, Lachnospiraceae and Ruminococcaceae families were associated with multiple diseases (known as non-specific responders), which inspired us to obtain non-gastrointestinal cancer samples for future experimental design (Duvallet et al, 2017;Rezasoltani et al, 2018).…”

“…Some researchers observed an association of the group of Bacteroides and Prevotella with elevated IL17-producing cells in colon cancer and demonstrated that supernatant from Fn inhibited the bactericidal activities of Fp and Bb (Sobhani et al, 2011;Guo et al, 2018). Furthermore, beneficial microbes can contribute to several intestinal functions and protect the organ from pathogenic microorganisms, and the "pathogenic bacteria:probiotics" ratio generates a better effect than single organism model (Eslami et al, 2019;Malagón et al, 2019;Yang et al, 2020). Thus, the complementary effects between enriched and reduced microbes should be highlighted for further investigation.…”

“…In terms of the rate of screening compliance, stool DNA test is associated with higher patient acceptance owing to its simplicity. A preliminary calculation showed that combination of FIT and bacterial markers would avert up to 30% of total colonoscopies as well as save an estimated 77 million € per 100,000 participants (Malagón et al, 2019). Meanwhile, usage of residual buffer from FIT cartridges is feasible for microbiota-based analysis and could greatly ameliorate the cost (Baxter et al, 2016a;Gudra et al, 2019).…”