Abstract
BackgroundFecal immunochemical test (FIT), DNA mutation, DNA methylation, and microbial dysbiosis all showed promising in colorectal cancer (CRC) non-invasive detection. We assessed CRC detection with an assay combining all these strategies and investigated the effect of clinical features on the performance of this comprehensive test.MethodsWe performed a multidimensional analysis study using stool samples collected from 108 patients with CRC, 18 patients with colorectal adenoma, and 36 individuals with no evidence of colorectal disease. The multidimensional analysis of stool samples including FIT, stool DNA (sDNA) tests for three methylated genes (Septin9, NDRG4, BMP3) and three mutated genes (KRAS, BRAF, PI3KCA) using next generation sequencing as well as detection of stool bacteria level of Fusobacterium nucleatum and Parvimonas micra using qPCR method. We used a linear support vector classification model to analyze the data.ResultsThe sensitivity of FIT alone was 69.4% for CRC and 11.1% for adenoma. Separately, the sensitivity of the detection of intestinal bacteria, DNA mutation, and DNA methylation for CRC was 58.3, 50.0, and 51.9%, respectively. The combination of FIT and sDNA tests had a sensitivity of 81.5% for CRC (AUC: 0.93, better than FIT alone, P = 0.017) and 27.8% for adenoma with 94.4% specificity. Sensitivity of the multidimensional test to detect CRC with stage II (84.6%) and III (91.9%) CRC was relatively higher (88.2%) than that of patients with stage I (60.0%) and stage IV (75.0%) (P = 0.024). The rate of CRC detection increased with tumor size (P = 0.008) and age (P = 0.04). Interestingly, the rate of CRC detection was higher in smoking persons than non-smokers with marginal significance (P = 0.08).ConclusionsThe multidimensional assay of stool samples combining FIT and stool DNA tests further improved the diagnostic sensitivity for CRC. This could provide new approach for improvement of CRC screening and further demonstrations are warranted.
Highlights
Colorectal cancer (CRC) is the third most common cancer with over 1.2 million new patients per year and the fourth leading cause of cancer-related death worldwide [1]
The relative level of both Fusobacterium nucleatum and Parvimonas micra increased from no evidence of colorectal disease (NED), adenoma to CRC groups (Figure 1C)
Our result indicated that this multi dimensional stool model consisting of Fecal immunochemical test (FIT), three methylation markers, three mutation genes, and two bacteria relative levels reached 94.4% specificity and 81.5% sensitivity of CRC
Summary
Colorectal cancer (CRC) is the third most common cancer with over 1.2 million new patients per year and the fourth leading cause of cancer-related death worldwide [1]. Its incidence and mortality are steadily dwindling because of the application of programmatic screening, which has been demonstrated in numerous large, long-term follow-up studies. The Minnesota Colon Cancer Control Study showed a relative risk of 0.68 (95% CI: 0.56–0.82) among participants randomized to annual fecal occult blood test (FOBT) screening compared to the control group over 30 years of follow-up [3]. The Nurses’ Health Study and the Nottingham trial showed the use of colonoscopy/sigmoidoscopy and FOBT screening reduced colorectal cancer mortality [4]. Evidence supports and guidelines endorse several tests and strategies, and screening for colorectal cancer has been found to be cost-effective [5]. Fecal immunochemical test (FIT), DNA mutation, DNA methylation, and microbial dysbiosis all showed promising in colorectal cancer (CRC) non-invasive detection. We assessed CRC detection with an assay combining all these strategies and investigated the effect of clinical features on the performance of this comprehensive test
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