Research About The Relationship Between The Protein Expression Of ZNF139, Bcl-2, Bax And Caspase-3in Gastric Carcinoma And Patients’ Clinico-pathological Parameters

Gastric carcinoma is one common malignant tumors，and it is the secondin all cancer. Most cases diagnosed in clinic are advanced gastric carcinomawith poor prognosis for lacking of specific clinical symptoms and signs duringthe early stage of gastric carcinoma, and the5-year overall survival rate ofadvanced gastric cancer is lower than30%. The tumorigenesis and multidrugresistance in gastric carcinoma are all multitargets, multigene and multistepinvolved complex course, which remains largely unknown. Recently the roleof zinc finger proteins in tumor has arisen wide concern. One of thelargest gene families of zinc finger transcriptional factors in the humangenome is the Krüppel-type ZNF gene family. In recent years, studies haveindicated that many members of the KRAB-ZNF family can regulate thetranscription and translation of relative genes and then are involved intumorigenesis and multidrug resistance of tumors. ZNF139gene is one of theKrüppel-type ZNF gene family, which was found as a protein relatedtranscription.Its gene was located between7q21.3～q22.1.The expression ofZNF139was discovered is higher in gastric cancer tissue than other tissues inthe early days of the study, so the scientists guessed it maybe play a part inregulation of the tumorigenesis and multidrug resistance. However, there isless study on the relationship between the protein expression of ZNF139ingastric carcinoma and patients’ clinico-pathological parameters and thesignificance of prognosis at the stage of being.Objective: Immunohistochemistry staining and TUNEL were performedto evaluate the protein expression of ZNF139in gastric carcinoma and gastricmucosa adjacent to carcinoma, investigate the relationship between the proteinexpression of ZNF139in gastric carcinoma and patients’ clinico-pathological parameters and the significance of prognosis. And the correlation amongZNF139, Bcl-2, Bax and Caspase-3was also analyzed. This study maypreliminary discussion the mechanism of action of ZNF139in the occurrenceand development process of gastric carcinoma.Methods: The specimens of120cases with gastric carcinoma werecollected, which were received surgery and diagnosed finally with gastriccarcinoma from January,2005to march,2007. All the specimens of gastriccarcinoma and gastric mucosa adjacent to carcinoma wereimmunohistochemistry dyed for detecting the relationships between theprotein expression of them in gastric carcinoma and patients’clinico-pathological parameters and the significance of prognosis, and thecorrelation among their expression was also analyzed. TUNEL was performedin these tissues for the detection of apoptosis index. The results were analyzedfor the relationship with the expressions of ZNF139. SPSS13.0software wasadopted to carry out the data processing and analyses, and significance wasassessed in all experiments as a probability value of P<0.05.Results:1The protein expression of ZNF139in gastric carcinoma were higherthan that in gastric mucosa adjacent to carcinoma （P=0.002）. Theexpressions of ZNF139in gastric carcinoma were significantly correlated withTNM stages, depth of invasion, and lymphatic metatasis(P=0.041，0.003，0.020), but not related with patient sex and age and nerve or blood vesselinvaded （P=0.653,0.545,0.056）. The prognosis of patients that theexpressions of ZNF139were positive was poor. The expressions of ZNF139was one of independent factors that affect the prognosis of gastric carcinomapatients, the risk of death was2.444times in positive expressions of ZNF139than negative expression（P=0.014）. The result of TUNEL showed therelationship between the expressions of ZNF139with AI was negativecorrelation (P=0.000， rs=-0.700）.The positive expression of ZNF139inhibitsthe occurrence of cell apoptosis. 2The positive expression of Bcl-2protein increased following the grademalignancy of tumor differentiation. There were remarkable correlatedbetween the expressions of Bcl-2with depth of invasion, and lymphaticmetatasis（P=0.007，0.006）, but not related with nerve or blood vesselinvaded（P=0.093）. The results showed it had not relationship between theexpressions of Bcl-2with the prognosis of gastric carcinoma patients.3The positive expression of Bax protein reduced following the grademalignancy of tumor differentiation (P=0.003）. And The expressions of Baxin gastric carcinoma were not significantly correlated with TNM stages, depthof invasion, lymphatic metatasis and age and nerve or blood vessel invaded（P=0.133，0.629，0.694，0.699）.There was not correlation between theexpressions of Bax with the prognosis of gastric carcinoma patients.4The expression of Caspase-3in gastric carcinoma were significantlycorrelated with tumor differentiation（P=0.005），but not related with patientsex，TNM stages, depth of invasion, lymphatic metatasis and nerve or bloodvessel invaded （P=0.218,0.261,0.329,0.238,0.242）. The result showed thatit had not relationship between the expression of Caspase-3with the prognosisof gastric carcinoma patients（P=0.271）.5The expression of ZNF139in gastric carcinoma were not correlatedwith Bcl-2and Bax (P=0.763,0.539），but were significantly related withCaspase-3（P=0.000，rs=-0.383）.6There had negative relationship between Bcl-2and Bax(P=0.026，rs=-0.203),and the expression of Caspase-3in gastric carcinoma were notcorrelated with Bcl-2and Bax(P=0.290,0.063).Conclusions:1The protein expression of ZNF139in gastric carcinoma are higher thanthat in gastric mucosa adjacent to carcinoma. Its expressions in gastriccarcinoma are positive correlated with tumor differentiation, but negativecorrelated with TNM stages, depth of invasion, and lymphatic metatasis. Theresult shows it maybe play a part in the occurrence and development processof gastric carcinoma. 2The prognosis of patients that the positive expressions of ZNF139arepoor. The expressions of ZNF139are one of independent factors that affectthe prognosis of gastric carcinoma patients, it can become one of the prognosisindicators.3The result of TUNEL shows it is negative correlation between theexpressions of ZNF139with AI.The positive expressions of ZNF139maybeinhibit the occurrence of cell apoptosis.4Bcl-2is one of cell apoptosis inhibition genes, its positive rate ofprotein increases following the grade malignancy of tumor differentiation.There are significantly correlated between the expressions of Bcl-2with depthof invasion, and lymphatic metatasis, but not relates with nerve or bloodvessel invaded. It has no obvious correlation between the expressions of Bcl-2with the prognosis of gastric carcinoma patients.5The positive expression of Bax protein reduces following the grademalignancy of tumor differentiation. The result shows the expressions of Baxin gastric carcinoma are not significantly correlated with TNM stages, depth ofinvasion, lymphatic metatasis and age and nerve or blood vessel invaded.There is not correlation between the expressions of Bax with the prognosis ofgastric carcinoma patients.6The expression of Caspase-3in gastric carcinoma are significantlycorrelated with tumor differentiation，but not relates with patient sex，TNMstages, depth of invasion, lymphatic metatasis and nerve or blood vesselinvaded. The result shows it has not relation between the expressions ofCaspase-3with the prognosis of gastric carcinoma patients.7The expression of ZNF139in gastric carcinoma are significantlycorrelated with Caspase-3, but not relates with Bcl-2and Bax. ZNF139as oneof nuclear transcription factor controls the expression of Caspase-3, inhibitsthe activation of Caspase-3, delays cell apoptosis, thus affects the occurrenceand development process of gastric carcinoma. However, the specific mechanism still need to further experimental research.