The Correlation Between Prognosis And Expression Of DEK And COX Ⅳ In Human Colorectal Carcinoma

Colorectal cancer (CRC) is one of the most common malignancies in clinicaltreatment. Nearly eight million new colorectal cancer cases are diagnosed each yearglobally. Despite great improvement in the treatment of CRC, the prognosis of CRCpatients, especially those with metastatic colorectal cancer (mCRC) remains poor. Currentclinical and pathological parameters are not sufficient to precisely predict clinical outcomeof CRC. Therefore, it is urgent to explore novel molecular biomarkers to discriminatepatients with different molecular pathological profiles, thus helping the elucidation ofCRC carcinogenesis, the estimation of the prognosis of patients with CRC and theimprovement of individualized treatment strategies.This study screened two highly relevant candidate genes of CRC proto-oncogeneDEK and mitochondria labeled molecules COX IV for investigation. The expression ofDEK and COX IV was detected in colorectal cancer, and the correlation betweenprognosis and the expression of DEK and COX IV was discussed respectively.Background: In many human invasive tumors such as adult acute leukemia,retinoblastoma, hepatocellular carcinoma, bladder cancer, cervical cancer, malignant glioma and melanoma, DEK proteins were overexpressed, and are closely associated withthe development and the occurrence of cancer chemotherapy resistance mechanisms.Therefore, DEK is likely to become a new target for cancer biotherapy. Previous studieshave demonstrated that the expression of cytochrome c oxidase (COX) subunits encodedby mitochondrial DNA is elevated in colorectal cancer (CRC). However, the expression ofnuclear DNA-encoded COX IV and its clinical significance have not yet been investigated.So far, the relation of the pathogenesis, the prognosis and the expression of DEK and COXIV in patients with colorectal cancer is rarely reported.Objective: To detect the expression of DEK and COX IV in human colorectalcarcinoma by immunohistochemical techniques etc. And to analyze the correlationbetween prognosis and the expression of DEK and COX IV.Methods: Immunohistochemical SP method was used to test the expression of DEKgene in169cases of colorectal cancer tissue and para-carcinoma tissue，and statisticalanalysis software was used to analyze the correlation between DEK gene expression andprognostic significance in human colorectal carcinoma; COX IV expression was examinedin23paired CRC tissues and non-tumor colon mucosa as well as in six CRC cell lines byreal-time PCR and Western blot. In addition, we also detected COX IV expression in339CRC samples by immunohistochemistry and analyzed its clinical significance.Results: The expression rate of DEK in colorectal cancer tissue85/169(50.30%) wassignificantly higher than those in para-carcinoma tissue，28/169(16.57%). Differences arestatistically significant (P <0.0001). The level of DEK expression in the tumor tissues wasirrelevant to age，gender，differentiated degree，TNM stage and size，but significantlycorrelated with overall survival (OS)(P <0.05). COX IV expression was significantlyelevated at both the mRNA (P=0.05) and protein levels in CRC tissues. In CRC cell lines,although there were differences in the mRNA expression of COX IV, all cell lines showedrobust COX IV protein expression. Immunohistochemistry revealed that COX IVexpression was significantly increased in CRC tissues (P <0.001). Association analysisshowed that there was no significant association between COX IV expression and clinical parameters of patients except for gender (P=0.017). Moreover, we did not find anyassociation between COX IV expression and prognosis of CRC patients.Conclusion: DEK expression is closely related to the prognosis of colorectal cancer.There will be poor prognosis for colorectal cancer patients of high DEK expression. Ourfindings suggest that elevated COX IV expression may play an important role in colorectalcarcinogenesis, which warrants further investigation in future.