Down Regulation Of Hepatocyte Nuclear Factor4α And Its Function In Colonrectal Cancer

Objective: Colorectal is one of the common malignant tumors of the gastrointestinaltract, to find some molecular mechanism early changed in colorectal cancer helps earlydiagnosis and intervention. Hepatocyte nuclear factor4α has an important role in themaintenance of normal morphology of the epithelial cells.The study is to detecthepatocyte nuclear factor4α expression in colorectal cancer tissue both at the mRNA andprotein levels, to find hepatocyte nuclear factor4α expression change in colorectal cancerand its clinical significance.Methods: We collect colorectal surgical specimens, extract specimens total RNAand reverse transcribed it into cDNA. Real-Time PCR was used to detect the hepatocytenuclear factor4α expression in colorectal tumor and paraneoplastic relatively normaltissue and immunohistochemical methods were used to detect hepatocyte nuclear factor4α expression on protein level and its subcellular localization. The statistical methodswere used to find correlations between HNF4α expression and clinical information.Results: Compared with the corresponding paraneoplastic relatively normalmucosal tissue, HNF4α was low expressed at the transcriptional level in36(62.07%) of58patients with an average of0.75times lower (P <0.05) and it was correlated with Tstage (the depth of tumor invasion)（P=0.03）while it did not have a statisticallysignificant correlation with the patient’s age, gender,tumor location, lymph node anddistant metastasis, differentiation, pathology type, clinical stage and other factors. Onprotein level,9of the10cases of intestinal inflammatory tissue showed cell nucleuspositive(90%), cytoplasm negative. The staining score is6.10of14cases of benignhyperplastic polyps and adenomas showed nucleus-positive (71.43%), cytoplasmnegative. The score is4-5, others were nucleus negative.6of11cases of adenoma andsevere dysplasia (carcinoma in situ,0stage) showed the nucleus positive (54.55%), Thescore is4-5. Two cases of villous gland carcinomatous patients showed cytoplasmpositive, The score is4-5. One is both nucleus and cytoplasm positive while another isnucleus negative but cytoplasm positive.13of19cases of phaseⅠcolorectal cancerpatients showed nucleus-positive (68.42%), the score is3-4, other cases were negative.10of the19cases showed cytoplasm positive(52.63%) and five were both nucleus andcytoplasm positive. The cytoplasm staining is less and dark while the nucleus staining ismore and shallow.6cases of10Phase Ⅱ patients showed nuclei positive, the score is1-2,no cytoplasmic positive cases.14cases of20Phase Ⅲ patients showed nuclei positive(70%), the score is1-2,no cytoplasmic positive cases.6cases of8Phase Ⅳpatients showed nuclei positive(70%), the score is1-2and no cytoplasmic positivecases.Conclusion: HNF4α was low expressed in human colorectal cancer ontranscriptional level and was associated with the depth of tumor invasion.In early stage ofcolorectal cancer, HNF4α protein was downregulated or lost and mislocated in thecytoplasm.It suggested that HNF4α may closely relate to colorectal tumorigenesis...