Novel DNA methylation biomarkers in stool and blood for early detection of colorectal cancer and precancerous lesions.

BACKGROUND: Early detection and prevention of precancerous lesions can significantly reduce the morbidity and mortality of colorectal cancer (CRC). Here, we developed new candidate CpG site biomarkers for CRC and evaluated the diagnostic value of their expression in blood and stool samples of CRC and precancerous lesions. METHODS: We analyzed 76 pairs of CRC and adjacent normal tissue samples, 348 stool samples, and 136 blood samples. Candidate biomarkers for CRC were screened using a bioinformatics database and identified using a quantitative methylation-specific PCR method. The methylation levels of the candidate biomarkers were validated using blood and stool samples. The divided stool samples were used to construct and validate a combined diagnostic model and to analyze the independent or combined diagnostic value of candidate biomarkers in stool samples of CRC and precancerous lesions. RESULTS: Two candidate CpG site biomarkers for CRC, cg13096260 and cg12993163, were identified. Although both biomarkers demonstrated diagnostic performance to a certain extent when using blood samples, they showed better diagnostic value for different stages of CRC and AA with stool samples. CONCLUSIONS: cg13096260 and cg12993163 detection in stool samples could be a promising approach for screening and early diagnosis of CRC and precancerous lesions.

ATG16L2 inhibits NLRP3 inflammasome activation through promoting ATG5-12-16L1 complex assembly and autophagy.

NLRP3 inflammasome activation is regulated by autophagy, a process tightly controlled by the ATG16L family proteins. However, the inside mechanisms remain elusive. Although the autophagy-related protein ATG16L1 has been well characterized, regulation and biological functions of its close homolog ATG16L2 still remain elusive. Here we report that ATG16L2 deficiency attenuates LPS-induced autophagy flux in macrophages through mediating ATG5-12-16L1 complex assembly. Importantly, NLRP3 inflammasome activation is elevated in ATG16L2-deficient macrophages, which also have defects in mitochondrial integrity and respiration. Finally, ATG16l2 knockout mice are more susceptible to DSS-induced intestinal damage, which can be ameliorated by inhibition of NLRP3. Collectively, our data demonstrate that ATG16L2 positively regulates autophagy and ATG16L2 could be a potential target for manipulating aberrant NLRP3 inflammasome activation induced inflammatory diseases.