Research On The Expression And Association Of WWOX Tumor Suppressive Gene And Nrf2Transcription Factor In The Gallbladder Carcinoma

Objective: Primary gallbladder carcinoma （PGC）is a highly malignant neoplasmand difficulant in early diagnosis, so it represents a very poor prognosis. In order toenhance the rate of long-term survival and the quality of patients’rest life, we should notonly try to rise the rate of early diagnosis of PGC, specify the operation, modify thetreatment of radiochemotherapy after operation, but also identify the molecular changesinvolved in the pathogenesis of PGC. However, there is limited information about themolecular abnormalities involved in its pathogenesis. To investigate expressions ofWWOX tumor suppressive gene and Nrf2transcription factor protein in gallbladdercarcinoma and analyze its relation with Clinical Pathology， to explore its role in the PGC,development, and analysis of correlation between the expression of WWOX and Nrf2protein, to explore its clinical significance. Methods: Expressions of WWOX and Nrf2protein in54cases of primary gallbladder carcinoma were determined by animmunohistochemistrical staining technique (SP method),20cases of adenoma ofgallbladder and of chronic cholecystitis tissues were collected as contrast, respectively. Atthe same time, the Clinical Pathology data from patients with carcinoma of gallbladder wascollection and analyzed the results. Results:(1)The positive expression rate of WWOX inchronic cholecystitis was85.0%(17/20),in adenoma of gallbladder was75.0%(15/20),which were higher than in carcinoma of gallbladder(48.1%,26/54), there wassignificant difference (χ~2=10.289，P<0.01);The positive expression rate of Nrf2ingallbladder carcinoma was66.7%(36/54),whice was significantly highter than that inadenoma of gallbladder(20.0%,4/20)and in chronic cholecystitis (5.0%,1/20), there wassignificant difference (χ~2=28.330，P<0.01).(2) In the Pathology grade of gallbladdercarcinoma, The positive expression rate of WWOX was72.7%(16/22) inwell-differentiated tissue, which was significantly higher than that of42.1%(8/19) inmoderately-differentiated tissue,15.4%(2/13) in poorly－differentiated tissue, there was significant difference (χ~2=11.191，P<0.01). The positive expression rate of Nrf2was45.5%(10/22) in well-differentiated tissue, which was significantly lower than that of73.7%(14/19) in moderately-differentiated tissue,92.3%(12/13) in poorly-differentiatedtissue, there was significant difference (χ~2=8.722，P<0.01).(3) In Nevin stage ofgallbladder carcinoma, The positive expression rate of WWOX was75.0%(3/4) for I stage,which was higher than that of Ⅱ stage72.7%(8/11), Ⅲ stage0(0), Ⅳ stage57.1%(8/14)and Ⅴ stage28.0%(7/25), there was significant difference (χ~2=4.738，P<0.05). The positive expression rate of Nrf2was25.0%(1/4) for I stage, which was lowerthan that of Ⅱ stage36.4%(4/11), Ⅲ stage was none, Ⅳ stage50.0%（7/14）and Ⅴstage96.0%(24/25), there was significant difference (χ~2=10.385，P<0.01).(4) The positive expression rate of WWOX was82.3%(14/17) in the absence oflymph node metastasis in gallbladder carcinoma tissue, which was higher than that of32.4%(12/37) in lymph node metastasis(χ~2=4.267，P<0.05); The positive expressionrate of Nrf2was23.5%(4/17) in the absence of lymph node metastasis in gallbladdercarcinoma tissue, which was lower than that of86.5%(32/37) in lymph node metastasis(χ2=8.022，P<0.01)(5) The positive expression rate of WWOX was34.2%(13/38) in theinfiltration gallbladder carcinoma tissue, which was significantly lower than that of81.3%(13/16) in no infiltration of gallbladder carcinoma tissue (χ~2=5.063，P<0.05); Thepositive expression rate of Nrf2was25.0%(4/16) in the no infiltration of gallbladdercarcinoma tissue, which was significantly lower than that of84.2%(32/38) in infiltration ofgallbladder carcinoma tissue (χ~2=9.091，P<0.01)(6) The positive expression of WWOXand Nrf2were no significant relationship and pathological types of patient’s gender, age,and is associated with stones (P>0.05).There was negative correlation between WWOXand Nrf2expression (r=－0.420,χ~2=9.490，P<0.01).Conclusion: The expressive levels of WWOX and Nrf2might be importantbiological markers for reflection the carcinogenesis, progression, biological behaviors；Both expressions of WWOX and Nrf2protein in gallbladder carcinoma have significantcorrelation, suggesting they may play a synergistic effect in the carcinogenesis ofgallbladder carcinoma.