SET7 interacts with HDAC6 and suppresses the development of colon cancer through inactivation of HDAC6.

SET7 is the first lysine methyltransferase and plays vital roles in tumorigenesis. This study aims to seek clinical value of SET7 in colorectal cancer (CRC) patients, along with its biological impact on cell proliferation and migration. In patients with CRC, the expression of SET7 in cancer tissue was significantly lower than that in adjacent tissue, and down-regulated SET7 was closely correlated with poor prognosis. Loss-of-function and gain-of-function studies indicated that SET7 inhibited cell proliferation and migration by acting on HDAC6 substrate in colon cancer cells. Besides, the co-immunoprecipitation assay showed that SET7 and HDAC6 can interact reciprocally. The interaction effect between SET7 and HDAC6 could significantly reduce cell viability, scratch healing rate, and migrated cells in colon cancer cells. Instead of acting on each endogenous expression, the results demonstrated that the level of acetylated α-tubulin was greatly decreased in HDAC6 overexpression group, while significantly increased in SET7 overexpressed group. However, changes were partly restored in both SET7 and HDAC6-transfected group. On the contrary, the expression of acetylated α-tubulin protein was significantly increased in HDAC6 knockdown group, but higher in both HDAC6 and SET7 silencing group. These results indicated that SET7 played a role in tumor suppression via increasing levels of acetylated-α-tubulin mediated by HDAC6. In addition, the interaction effect significantly decreased the ratios of p-ERK/ERK, which indicated that it may partly suppress ERK signaling pathway. In conclusion, SET7 is a promising therapeutic target for preventing metastasis and improving prognosis in colon cancer.

Efficacy of noninvasive evaluations in monitoring inflammatory bowel disease activity: A prospective study in China.

AIM: To optimize the efficacy of noninvasive evaluations in monitoring the endoscopic activity of inflammatory bowel disease (IBD). METHODS: Fecal calprotectin (FC), clinical activity index (CDAI or CAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) were measured for 136 IBD patients. Also, FC was measured in 25 irritable bowel syndrome (IBS) patients that served as controls. Then, endoscopic activity was determined by other two endoscopists for colonic or ileo-colonic Crohn's disease (CICD) with the "simple endoscopic score for Crohn's disease" (SES-CD), CD-related surgery patients with the Rutgeerts score, and ulcerative colitis (UC) with the Mayo score. The efficacies of these evaluations to predict the endoscopic disease activity were assessed by Mann-Whitney test, χ2 test, Spearman's correlation, and multiple linear regression analysis. RESULTS: The median FC levels in CD, UC, and IBS patients were 449.6 (IQR, 137.9-1344.8), 497.9 (IQR, 131.7-118.0), and 9.9 (IQR, 049.7) µg/g, respectively (P < 0.001). For FC, CDAI or CAI, CRP, and ESR differed significantly between endoscopic active and remission in CICD and UC patients, but not in CD-related surgery patients. The SES-CD correlated closely with levels of FC (r = 0.802), followed by CDAI (r = 0.734), CRP (r = 0.658), and ESR (r = 0.557). The Mayo score also correlated significantly with FC (r = 0.837), CAI (r = 0.776), ESR (r = 0.644), and CRP (r = 0.634). For FC, a cut-off value of 250 µg/g indicated endoscopic active inflammation with accuracies of 87.5%, 60%, and 91.1%, respectively, for CICD, CD-related surgery, and UC patients. Moreover, clinical FC activity (CFA) calculated as 0.8 × FC + 4.6 × CDAI showed higher area under the curve (AUC) of 0.962 for CICD and CFA calculated as 0.2 × FC + 50 × CAI showed higher AUC (0.980) for UC patients than the FC. Also, the diagnostic accuracy of FC in identifying patients with mucosal inflammation in clinical remission was reflected by an AUC of 0.91 for CICD and 0.96 for UC patients. CONCLUSION: FC is the most promising noninvasive evaluation for monitoring the endoscopic activity of CICD and UC. CFA might be more accurate for IBD activity evaluation.

Meta-analysis: fecal calprotectin for assessment of inflammatory bowel disease activity.

BACKGROUND: Fecal calprotectin (FC) is a promising biomarker for diagnosis of inflammatory bowel disease (IBD). However, the utility of FC for assessment of IBD activity has yet to be clearly demonstrated. The aim of our study was to evaluate the diagnostic accuracy of FC for differentiating between patients with active IBD and those in remission. METHODS: We systematically searched the databases Medline, Web of Science, Cochrane Library, and EMBASE for eligible studies from December 2013 or earlier that evaluated activity in ulcerative colitis (UC) and Crohn's disease (CD). A hierarchical summary receiver operating characteristic model was performed to calculate the area under the curve to evaluate the overall diagnostic accuracy. The sensitivities and specificities of each commonly applied cutoff value were pooled using a random effects model. RESULTS: We included 13 studies (744 patients with UC and 727 with CD) in the final analysis. The area under the curve values were 0.89 (95% confidence interval, 0.86-0.92), 0.93 (0.89-0.97), and 0.88 (0.83-0.93) in the IBD, UC, and CD groups, respectively. For the IBD group at a cutoff value of 50 µg/g, the pooled sensitivity was 0.92 (0.90-0.94) and specificity 0.60 (0.52-0.67). For a cutoff value at 100 µg/g, the pooled sensitivity was 0.84 (0.80-0.88) and specificity was 0.66 (0.59-0.73). For a cutoff value at 250 µg/g, the pooled sensitivity was 0.80 (0.76-0.84) and specificity was 0.82 (0.77-0.86). CONCLUSIONS: The FC test is a reliable marker for assessing IBD disease activity and may have greater ability to evaluate disease activity in UC than CD.