Objective To construct and verify a genetically engineered mouse model which is similar to clinical sporadic colorectal cancer and simultaneously expresses KrasLSL-G12D/- and Smad4loxp/loxp genes. Methods The Krastm4Tyj/J mouse and Smad4tm2.1Cxd/J mouse were transformed into the genetic background, and the genotypes of the offspring mice were identified by the PCR to obtain the mice expressed simultaneously KrasLSL-G12D/- and Smad4loxp/loxp genes. The LentivirusCre-IRES-Luciferase was injected into the submucosa of the model mice and the tumorigenicity was observed under the IVIS system. The tumor tissues of the model mice were sampled and the HE staining was used to verify the tumorigenicity of the model mice. Results The genetically engineered mouse model which could simultaneously express KrasLSL-G12D/- and Smad4loxp/loxp genes was obtained by the breeding and selection. The mouse intestinal epithelial cell carcinogenesis was successfully induced by the viral vector containing Cre recombinase. Conclusion Mouse model expressed simultaneously KrasLSL-G12D/- and Smad4loxp/loxp genes is capable of sporadic tumorigenicity by Cre recombinase and could simulate pathological process of human sporadic colorectal cancer.
ObjectiveTo analyze expressions of interleukin-6 (IL-6) and microsatellite instability (MSI) in ulcerative colitis-associated colorectal cancer (UC-CRC) and investigate role of IL-6 and MSI in carcinogenesis of patients with UC.MethodsThe postoperative pathological data of patients with UC-CRC and patients with sporadic colorectal cancer (SCRC) admitted by Edong Healthcare Group from January 2013 to January 2019 were analyzed retrospectively. The expressions of MMR proteins, including hMLH1, hPMS2, hMSH2, and hMSH6, were detected by the immunohistochemical method. The serum IL-6 levels of the patients with UC, UC-CRC, SCRC and control patients (non-UC, non-UC-CRC, non-SCRC) were detected. The correlation between the IL-6 and MMR protein expression in the cancer tissue was analyzed.ResultsThere were 43 patients with UC, 17 UC-CRC, 55 SCRC, and 30 control patients. The total rate of MMR-deficient (dMMR) was 41.2% (7/17) in the patients with UC-CRC. There were significant correlations between the hMLH1 and hPMS2 protein expression deletion and between the hMSH2 and hMSH6 protein expression deletion (P<0.001). The serum level of IL-6 in the patients with UC-CRC was significantly higher than that in the patients with UC (t=4.97, P<0.001) and the patients with SCRC (t=5.26, P=0.006). The dMMR might be associated with the level of IL-6 in the patients with UC-CRC, which wasn’t associated with it in the patients with SCRC (rs=0.04, P=0.77).ConclusionsSimilar to SCRC, MSI also plays a role in occurrence and development of UC-CRC. dMMR in patient with UC-CRC is more common in co-expression deficiency of hMLH1 and hPMS2, as did hMSH2 and hMSH6. IL-6 is not involved in mechanism of MSI-related canceration of colorectal cancer, but it is speculated that IL-6 might be involved in occurrence of MSI of UC-CRC.