Multiple-matrix metabolomics analysis for the distinct detection of colorectal cancer and adenoma.

OBJECTIVES: Although colorectal cancer (CRC) is the leading cause of cancer-related morbidity and mortality, current diagnostic tests for early-stage CRC and colorectal adenoma (CRA) are suboptimal. Therefore, there is an urgent need to explore less invasive screening procedures for CRC and CRA diagnosis. METHODS: Untargeted gas chromatography-mass spectrometry (GC-MS) metabolic profiling approach was applied to identify candidate metabolites. We performed metabolomics profiling on plasma samples from 412 subjects including 200 CRC patients, 160 CRA patients and 52 normal controls (NC). Among these patients, 45 CRC patients, 152 CRA patients and 50 normal controls had their fecal samples tested simultaneously. RESULTS: Differential metabolites were screened in the adenoma-carcinoma sequence. Three diagnostic models were further developed to identify cancer group, cancer stage, and cancer microsatellite status using those significant metabolites. The three-metabolite-only classifiers used to distinguish the cancer group always keeps the area under the receiver operating characteristic curve (AUC) greater than 0.7. The AUC performance of the classifiers applied to discriminate CRC stage is generally greater than 0.8, and the classifiers used to distinguish microsatellite status of CRC is greater than 0.9. CONCLUSION: This finding highlights potential early-driver metabolites in CRA and early-stage CRC. We also find potential metabolic markers for discriminating the microsatellite state of CRC. Our study and diagnostic model have potential applications for non-invasive CRC and CRA detection.

Efficacy and safety of Shenbai Granules for recurrent colorectal adenoma: A multicenter randomized controlled trial.

BACKGROUND: Colorectal adenoma is benign glandular tumor of colon, the precursor of colorectal cancer. But no pharmaceutical medication is currently available to treat and prevent adenomas. PURPOSE: To evaluate efficacy of Shenbai Granules, an herbal medicine formula, in reducing the recurrence of adenomas. STUDY DESIGN: This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted by eight hospitals in China. METHODS: Patients who had received complete polypectomy and were diagnosed with adenomas within the recent 6 months were randomly assigned (1:1) to receive either Shenbai granules or placebo twice a day for 6 months. An annual colonoscopy was performed during the 2-year follow-up period. The primary outcome was the proportion of patients with at least one adenoma detected in the modified intention-to-treat (mITT) population during follow-up for 2 years. The secondary outcomes were the proportion of patients with sessile serrated lesions and other specified polypoid lesions. The data were analyzed using logistic regression. RESULTS: Among 400 randomized patients, 336 were included in the mITT population. We found significant differences between treatment and placebo groups in the proportion of patients with at least one recurrent adenoma (42.5 % vs. 58.6 %; OR, 0.47; 95 % CI, 0.29-0.74; p = 0.001) and sessile serrated lesion (1.8 % vs. 8.3 %; OR, 0.20; 95 % CI, 0.06-0.72; p = 0.01). There was no significant difference in the proportion of patients developing polypoid lesions (70.7 % vs. 77.5 %; OR, 1.43; 95 % CI, 0.88-2.34; p = 0.15) or high-risk adenomas (9.0 % vs. 13.6 %; OR, 0.63; 95 % CI, 0.32-1.25; p = 0.18). CONCLUSION: Shenbai Granules significantly reduced the recurrence of adenomas, indicating that they could be an effective option for adenomas. Future studies should investigate its effects in larger patient populations and explore its mechanism of action to provide more comprehensive evidence for the use of Shenbai Granules in adenoma treatment.