| Objective:Colorectal carcinoma is one of the most common digestivecarcinomas. Around the world, there is an upward trend in morbidity andmortality of colorectal cancer, which has seriously affected people’s health andlife. The cause of colorectal carcinoma has not been clarified, and most peoplethink that it is likely to be caused by both genetic and environmental factors.Most of the colorectal carcinomas result from colorectal adenoma, which isregarded as precancerous lesions.It is usually that the larger the colorectaladenoma is,and the more the villus it contains, following by the higher risk forcolorectal adenoma to develop into carcinoma, so strengthening theunderstanding of malignant transformation about adenoma is the key to reducethe incidence of colorectal cancer.Pokemon (POK erythroid myeloid ontogenic actor), also known asZBTB7A,OCZF,FBI-1and, is initially found as the special binding protein ofHIV-1promoter, and it is the first transcription inhibitor about alterativereading frame. Pokemon promotes cell proliferation in tumors through thepath of Pokemon↑â†'ARF↓â†'MDM2â†'P53↓, and it can also inhibit thetranscription of Rb gene and adjust its targets and pathways through theubiquitination about the protein to participate in the transcription of somegenes. As the main switch of the tumor, the particularity about it is that it islocated in the upstream of a wide variety of tumor suppressor genes andproto-oncogenes.As a tumor suppressor gene,TIP30inhibits the proliferation of cellsthrough the P53pathway. Because the cells are blocked in the period ofG0-G1, the number of the cells in the period of S declines. TIP30promotesapoptosis by regulating Bad, Bax gene, and it also can prevent spread of thetumor by deregulating VEGF. Osteopontin (OPN) promotes the tropism, adherency, migration of the cells, combining with CD44and integrins. OPNshows high expression in a wide variety of tumor cells. TIP30inhibits theaction of the tumors by reducing the expression of osteopontin.The aim of this study is to detect the expression levels of Pokemon andTIP30in colorectal carcinoma, colorectal adenomas(tubular adenoma, mixedpattern of adenoma, villous adenoma), normal colorectal mucosa, and analyzethe relationships among different histological types of colorectal adenomasand colorectal carcinoma. It will provide the new clue for the early diagnosisand gene therapy for the tumors.Materials and Methods:We collected60colorectal carcinoma tissuesafter surgical resection and40normal colorectal mucosa tissues(adjacent tocarcinoma, at least5cm away from the cancer tissue from the stump of thesurgery)during January2012to June2013.None of the60patients underwentpreoperative chemotherapy, radiation or targeted therapy before surgicalresection.80colorectal adenomas including30tubular adenoma,30mixedpattern of adenoma,20villous adenoma were collected from endoscopy centerof252hospital. All the specimens were reviewed and filtrated by senior doctorin the pathology department.HE staining was used to observe pathological types and the degree ofhistological differentiation. Immunohistochemistry was used to detect thelocation and expression of Pokemon, TIP30in the tissues.Using fluorescencequantitative polymerase chain reaction (PCR) to detect Pokemon mRNA andTIP30mRNA expression.The results were analyzed by chi-square criterion analysis and One-wayanalysis of variance with SPSS18.0. The test was considered to be statisticallysignificant when P<0.05.Results:The results of the immunohistochemistry were that the positiveexpression rates of Pokemon protein in normal colorectal mucosa, colorectaladenoma and colorectal carcinoma tissues are25%,51.2%,80%, respectively,with significant differences among them(P<0.05). The positive expressionrates of Pokemon in tubular adenoma, mixed pattern of adenoma, villous adenoma were33.3%,53.3%,75%, respectively, also with significantdifferences among them(P<0.05). There was a significant correlation betweenraised expression of Pokemon and unfavorable variables, including nodalmetastasis, Dukes stage, differentiation degree. There was no obviousdifference in age and sex. The positive expression rates of TIP30in normalcolorectal mucosa, colorectal adenoma and colorectal carcinoma tissues were95%,67.5%,30%, respectively, with significant differences among them(P<0.05). The positive expression rates of TIP30in tubular adenoma, mixedpattern of adenoma, villous adenoma were86.7%,66.7%,40%,respectively,also with significant differences among them(P<0.05). There was a significantcorrelation between reduced expression of TIP30and unfavorable variables,including nodal metastasis, Dukes stage, differentiation degree.There was noobvious difference in age and sex.Fluorescence quantitative PCR showed characterized amplification aboutPokemon, and the Pokemon mRNA expression of the normal colorectalmucosa, tubular adenoma, the mixed pattern of adenoma, villous adenoma,and colorectal carcinoma are0.981±0.189,2.024±0.226,3.357±0.262，5.006±0.281，6.450±0.216，respectively. The expression of Pokemon graduallyincreased in normal colorectal mucosa, tubular adenoma, mixed pattern ofadenoma, villous adenoma and colorectal carcinoma. F=432.884，P<0.05.SNK multiple comparisons displayed that the differences about any twogroups of the total mean showed statistical significance. TIP30specificallyamplify, and the TIP30mRNA expression of the normal colorectal mucosa,tubular adenoma, the mixed pattern of adenoma, villous adenoma, colorectalcarcinoma are25.135±1.474，18.701±1.596，12.412±1.677，6.579±0.795，2.137±0.535，respectively. The expression of TIP30gradually decreased innormal colorectal mucosa, tubular adenoma, mixed pattern of adenoma,villous adenoma and colorectal carcinoma. F=250.931, P<0.05.SNK multiplecomparisons displayed that the differences about any two groups of the totalmean showed statistical significance.Conclusion:The expression of Pokemon in normal colorectal mucosa was weak,and TIP30was strong. As the villus grows higher in adenoma, theexpression of Pokemon presented a gradual upward trend, though theexpression of TIP30showed a gradual decrease. Pokemon showed highestexpression level in colorectal carcinoma, though the expression of TIP30wasin the minimum amount. Pokemon and TIP30may participate in theoccurrence and development of colorectal adenoma and colorectal carcinoma.By detecting the expression of Pokemon and TIP30, we can evaluate theprogression of colorectal adenoma and the development of colorectalcarcinoma. Pokemon and TIP30may be the molecular biological indicatorsfor predicting malignant transformation of colorectal adenoma. |
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