Overexpression of p42.3 promotes cell growth and tumorigenicity in hepatocellular carcinoma

AIM:To investigate the association of p42.3 expression with clinicopathological characteristics and the biological function of p42.3 in human hepatocellular carcinoma(HCC).METHODS:We used reverse transcription-polymerase chain reaction(RT-PCR),quantitative real-time RT-PCR and western blotting to detect p42.3 mRNA and protein expression in hepatic cell lines.We examined primary HCC samples and matched adjacent normal tissue by immunohistochemistry to investigate the correlation between p42.3 expression and clinicopathological features.HepG2 cells were transfected with a pIRES2EGFP-p42.3 expression vector to examine the function of the p42.3 gene.Transfected cells were analyzed for their viability and malignant transformation abilities by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,colony formation assay,and tumorigenicity assay in nude mice.RESULTS:p42.3 is differentially expressed in primary HCC tumors and cell lines.Approximately 69.6%(96/138) of cells were p42.3-positive in hepatic tumor tissues,while 30.7%(35/114) were p42.3-positive in tumor-adjacent normal tissues.Clinicopathological characteristics of the HCC specimens revealed a significant correlation between p42.3 expression and tumor differentiation(P = 0.031).However,p42.3 positivity was not related to tumor tumor-node-metastasis classification,hepatitis B virus status,or hepatoma type.Regarding p42.3 overexpression in stably transfected HepG2 cells,we discovered significant enhancement of cancer cell growth and colony formation in vitro,and significantly enhanced tumorigenicity in nude mice.Western blot analysis of cell cycle proteins revealed that enhanced p42.3 levels promote upregulation of proliferating cell nuclear antigen,cyclin B1 and mitotic arrest deficient 2.CONCLUSION:p42.3 promotes tumorigenicity and tumor growth in HCC and may be a potential target for future clinical cancer therapeutics.

Low prevalence of mismatch repair deficiency in Chinese colorectal cancers:a multicenter study

Background:Although universal testing for mismatch repair deficiency(dMMR)has been recommended to all colorectal cancer(CRC)patients,related evidence for the Chinese population is lacking.Here,we investigated the prevalence and clinicopathological features of dMMR patients in a large Chinese CRC cohort.Methods:We included 7,373 CRC patients treated at four Chinese medical centers between August 2010 and September 2016.Patients’baseline characteristics and pathological features were recorded.The clinicopathological features were compared between patients with MLH1/PMS2 deficiency(dMLH1/PMS2)and MSH2/MSH6 deficiency(dMSH2/MSH6).Results:Among the investigated patients,654(8.9%)were identified with dMMR CRCs and,of them,401(61.3%)were males,with a median age of 55 years(range,22-87 years);355(54.3%)had stage II CRC based on American Joint Committee on Cancer 8th edition.The prevalence of the dMLH1/PMS2 group and the dMSH2/MSH6 group were 51.5%(337/654)and 25.1%(164/654),respectively.Compared with dMSH2/MSH6 patients,those with dMLH1/PMS2 were older(57 vs 52 years,P<0.001),more likely to be female(45.7%vs 31.5%,P=0.004),prone to having tumors located in the right-hand side of the colon(59.0%vs 47.6%,P=0.015),and less likely to have a family history of tumors(29.7%vs 43.3%,P=0.003).Conclusions:The prevalence of dMMR in Chinese CRC patients was low,especially in the dMLH1/PMS2 group.The clinicopathological features were different between dMMR subgroups.