Expression and Significance of WWOX and FHIT in Colorectal Cancer

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Tumor Research

[Abstract]

Objective: The fragile sites and fragile-site-related genes play animportant role in the process of tumorigenesis and malignanttransformation in human malignancies(including digestive tract cancers).Two candidate tumor suppressor genes, fragile histidine triad(FHIT) andWW domain-containing oxidoreductase (WWOX), have been found tospan the FRA3B and FRA16D, respectively, but FRA3B and FRA16Dare the most frequently expressed of the common chromosomal fragilesite loci. It is reported that the expression of WWOX and FHITgenes is decreased coordinately in several cancers, but it remainsuncertain in colorectal cancer. The purpose of this study is to investigatethe expression of WWOX and FHIT in colorectal cancer, to explorerelationship between WWOX and FHIT expression and clinicalpathologic parameters, and to investigate the coordination of WWOX andFHIT expression in colorectal cancer.Methods: Expression of WWOX and FHIT is evaluated byimmunohistochemical staining (two-step method) in 75 colorectal carcinoma specimens and 30 cases normal colorectal tissues, and theircorrelation with clinicopathological features was analyzed. Cox modelhas been used to calculate the survival.Results: The rate of WWOX and FHIT positive expression intumors is observed in 52% and 54.7% of specimens, respectively, whichis significantly different from that in normal colorectal tissues as 93.3%and 97.8%. WWOX and FHIT expression is correlated strongly(P?0.05).Expression of WWOX and FHIT is closely associated with histologicalgrade and Duke? stage. By Cox?s proportional hazard model analysis,histological grade and Duke stage and expression of WWOX areconsidered an independent predictor for the prognosis of the colorectalcancer. The follow-up data of 72 cases showed that 5-year survival group,27 of 40 are of the positive WWOX expression carcinomas, 30 of 40 areof the positive FHIT expression carcinomas, while in the 5-year deadgroup, 11 of 32 of are of the positive WWOX expression carcinomas, 10of 32 are of the positive FHIT expression carcinomas, and there is asignificant difference (p?0.05).Conclusion: The expression of WWOX and FHIT is lower incolorectal cancer than that in normal tissues. There is closely associatedwith histological grade, Dukes stage, and 5-year survival rate (P?0.05).Expression of WWOX and FHIT was correlated strongly (P?0.05). Thiscorrelation is consistent with the susceptibility of common fragile sites to DNA damage. It is suggested that WWOX and FHIT genes may play animportant role in the initiation and development of colorectal cancer.They can become targets of predicting the progression of colorectalcancer.

Title: Expression and Significance of WWOX and FHIT in Colorectal Cancer

Category: Tumor Marker

Filename: Expression and Significance of WWOX and FHIT in Colorectal Cancer.pdf

Pages: 179

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