Improved diagnosis of colorectal cancer using combined biomarkers including Fusobacterium nucleatum, fecal occult blood, transferrin, CEA, CA19-9, gender, and age.

BACKGROUND: Conventional blood and stool tests are normally used for early screening of colorectal cancer (CRC) but the accuracy and efficiency remain to be improved. Recent findings suggest Fusobacterium nucleatum to be a biomarker for CRC. This study evaluated the role of F. nucleatum and developed CRC diagnostic models by combining F. nucleatum with fecal occult blood (FOB), transferrin (TRF), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), gender, and age. MATERIALS AND METHODS: Candidates including 71 healthy individuals and 59 CRC patients were recruited. Abundance of F. nucleatum in stool or tissue samples was measured by quantitative real-time PCR. CEA, CA19-9, TRF, and FOB were measured in parallel. These biomarkers together with genders and ages were the seven parameters used to develop CRC diagnostic models. Ten different machine learning algorithms were tested to achieve the best performance. RESULTS: Fecal F. nucleatum abundance was found significantly higher in CRC group compared to healthy group (p = 0.0005). Among the CRC patients, F. nucleatum abundance in tumor tissue was significantly higher than that in paracancerous tissue (p = 0.0087). CRC diagnostic models using different parameters were generated based on Logistic Regression algorithm, which showed good performance. The area under the curve (AUC) score of fecal F. nucleatum as the single diagnostic biomarker was 0.68 while the accuracy was 0.56. The diagnostic performance was obviously improved with the highest AUC (0.93) and accuracy (0.87) achieved when using all the 7 clinical parameters. The combination F. nucleatum + FOB + gender + age had the second highest AUC (0.92) and accuracy (0.85). A more utilitarian model using F. nucleatum + FOB showed relatively high AUC at 0.86 and accuracy at 0.81. CONCLUSIONS: F. nucleatum is valuable for CRC diagnosis. Combination of different clinical parameters could significantly improve CRC diagnostic performance. The combination F. nucleatum + FOB + gender + age may be an effective and noninvasive method for clinical application.

Donor polymorphisms of Rap1A rs494453 contribute to a higher risk of hepatocellular carcinoma recurrence following liver transplantation.

Background: Hepatocellular carcinoma (HCC) recurrence appears commonly after liver transplantation (LT), and it severely affected the long-term survival of patients. Previous studies have proved that Rap1A is involved in hepatocarcinogenesis and metastasis, and demonstrated the significant association between Rap1A gene rs494453 polymorphism and HCC. However, the relationship between Rap1A rs494453 polymorphism and HCC recurrence after LT remained unclear. Methods: A total of 74 HCC patients who underwent LT from July 2005 to June 2015 was analyzed. The genotypes of both donors and recipients had been confirmed as Rap1A rs494453. The independent risk factors that associated with HCC recurrence were investigated with univariate and multivariate logistic regression analysis. The recurrence-free (RFS) and overall survival (OS) were calculated with Cox regression analysis. The Rap1A rs494453 genotype frequencies were determined using the Χ² test and the minor allele frequencies (MAFs) of Rap1A rs494453 genotypes were calculated by Hardy-Weinberg equilibrium. Results: We found that the donor Rap1A rs494453 polymorphism was profoundly associated with HCC recurrence after LT. Moreover, the Milan criteria, microvascular invasion and donor Rap1A rs494453 genotype were proved to be independent risk factors for HCC recurrence. Patients with donor AG/GG genotypes had a distinct lower RFS and OS than AA genotype. The TNM stage, Milan criteria, microvascular invasion, and donor Rap1A rs494453 genotype were independent factors for the RFS of LT patients. Conclusions: Donor Rap1A rs494453 is a potential predictive marker for HCC recurrence risk after LT.