Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development.

OBJECTIVE: Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States. Recent cancer genome-sequencing efforts and complementary functional studies have led to the identification of a collection of candidate 'driver' genes involved in CRC tumorigenesis. Tripartite motif (TRIM3) is recently identified as a tumour suppressor in glioblastoma but this tumour-suppressive function has not been investigated in CRC. MATERIAL AND METHODS: In this study, we investigated the potential role of TRIM3 as a tumour suppressor in CRC development by manipulating the expression of TRIM3 in two authentic CRC cell lines, HCT116 and DLD1, followed by various functional assays, including cell proliferation, colony formation, scratch wound healing, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumour-suppressive properties of TRIM3. RESULTS: Small-interfering RNA (siRNA) mediated knockdown of TRIM3 conferred growth advantage in CRC cells. In contrast, overexpression of TRIM3 affected cell survival, cell migration, anchorage independent growth and invasive potential in CRC cells. In addition, TRIM3 was found to be down-regulated in human colon cancer tissues compared with matched normal colon tissues. Overexpression of TRIM3 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that TRIM3 can regulate p53 protein level through its stabilisation. CONCLUSIONS: TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. Therefore, this protein may represent a novel therapeutic target for prevention or intervention of CRC.

Reevaluation of a rightward shift in colorectal cancer: A single-center retrospective study in Tianjin.

OBJECTIVES: Some Western reports have shown a proximal shift in colorectal cancer (CRC), but there are few studies in China. This study aimed to provide more information for the management and screening of CRC by investigating trends in the anatomic distribution of CRC among the Chinese population in recent years. METHODS: A retrospective study was conducted on patients with CRC admitted to the Digestive Endoscopy Center of Tianjin Medical University General Hospital between January 2000 and December 2017. Patients were divided into a left-sided colorectal cancer (LSCRC) group and a right-sided colon cancer (RSCC) group. The detection rates of LSCRC and RSCC based on patients' age and sex, and on the time periods were analyzed. RESULTS: A total of 2319 cases were diagnosed with CRC among 75 183 consecutive patients. The prevalence of CRC showed a significant reduction from 2000-2008 to 2009-2017 (3.8% vs 2.7%, P < .001). The proportion of RSCC presented a downtrend from 2000-2008 to 2009-2017 (40.6% vs 37.7%, P > .05). There were slightly more RSCCs in female patients than in male patients, with no significant difference (40.9% vs 36.5%, P > .05). The proportion of RSCC in patients aged ≥50 years was similar to that in younger patients. The alarming symptoms between LSCRC and RSCC showed a significant difference (P < .05). CONCLUSIONS: In the present study, the prevalence of CRC declined significantly with time. However, there did not appear to be a rightward shift in CRC among the patients in Tianjin over the past 18 years.

Clinicopathological features of advanced colorectal serrated lesions: A single-center study in China.

OBJECTIVE: A growing body of evidence indicates that patients with colorectal serrated lesions, especially advanced serrated lesions (ASLs), are at risk of subsequent malignancy. This study aimed to analyze the clinicopathological features of ASLs and the association between ASLs and synchronous advanced colorectal neoplasia (sACN) in a single center of China. METHODS: A retrospective cross-sectional study of consecutive symptomatic patients and healthy individuals who underwent colonoscopy between January 2010 and March 2016 was performed. Clinicopathological characteritics of the patients with ASLs were documented from the colonoscopy database. RESULTS: Colorectal serrated lesions were pathologically confirmed in 277 (N = 38 981, 0.7%) cases. Among them, 156 (56.3%) were found to have ASLs, with a total of 161 lesions including 71 sessile serrated adenoma/polyps (SSA/P) and 90 traditional serrated adenomas (TSAs). There were no differences in age and gender between the ASL and non-ASL patients. Among the 161 ASLs, 29 (18.0%) were ≥10 mm in diameter. Compared with non-ASLs, ASLs appeared more in the proximal colon (P = 0.007). Flat and subpedunculated lesions were more commonly found in the ASL group compared with the non-ASL group. Nearly all ASLs (160/161) had dysplasia. Moreover, 16 sACN lesions were found in 156 ASL patients, and large diameter (≥10 mm) might be a significant risk factor for sACN (odds ratio 4.35, 95% confidence interval 1.467-12.894, P < 0.05). CONCLUSIONS: ASLs are more likely to occur in the proximal colon, and mainly present as flat and sub-pedunculated types. Large ASLs are significantly associated with sACN.

Clinical features of upper gastrointestinal serrated lesions: An endoscopy database analysis of 98746 patients.

AIM: To analyse the clinical features of patients with the serrated lesions in the upper gastrointestinal tract (UPGI) tract. METHODS: Patients who underwent routine esophagogastroduodenoscopy (EGD) at the Digestive Endoscopy Centre of General Hospital, Tianjin Medical University between January 2011 and December 2015 were consecutively recruited. Patients with UPGI serrated lesions were consecutively identified. The patients' demographics and histopathology were recorded. The colorectal findings for patients who underwent colonoscopy simultaneously or within six months were also extracted from the colonoscopy database. In addition, we analysed differences in colorectal neoplasia detection between the study patients and randomly selected patients matched for age and gender who did not exhibit serrated lesions and who also underwent colonoscopy in the same period. RESULTS: A total of 21 patients out of 98746 patients (0.02%) who underwent EGD were confirmed to have serrated lesions with predominantly crenated, sawtooth-like configurations. The mean age of the 21 patients was (55.3 ± 17.2) years, and 11 patients were male (52.4%). In terms of the locations of the serrated lesions, 17 were found in the stomach (including 3 in the cardia, 9 in the corpus and 5 in the antrum), 3 were found in the duodenum, and 1 was found in the esophagus. Serrated lesions were found in different mucosal lesions, with 14 lesions were detected in polyps (8 hyperplastic polyps and 6 serrated adenomas with low grade dysplasia), 3 detected in Ménétrier gastropathy, 3 detected in an area of inflammation or ulcer, and 1 detected in the intramucosal carcinoma of the duodenum. In addition, colonoscopy data were available for 18 patients, and a significantly higher colorectal adenoma detection rate was observed in the UPGI serrated lesions group than in the randomly selected age- and gender-matched group without serrated lesions who also underwent colonoscopy in the same period (38.9% vs 11.1%, OR = 5.091, 95%CI: 1.534-16.890, P = 0.010). The detection rate of advanced adenoma was also higher in the UPGI serrated lesions group (22.2% vs 4.2%, OR = 6.571, 95%CI: 1.322-32.660, P = 0.028). CONCLUSION: Serrated lesions in the UPGI were detected in various mucosal lesions with different pathological morphologies. Moreover colonoscopy is recommended for the detection of concurrent colorectal adenoma for these patients.