| Objective To investigate the expression of ER(endoplasmic reticulum)-derived transcription factor CHOP(C/EBP homology protein) in gastric cardia adenocarcinoma(GCA) and to analyze the relationship between the GCA patients and clinical stage, pathological grade and lymph node metastasis and prognosis significance.Methods 68 cases tissues of GCA collected from the Surgical Oncology of The First Affiliated Hospital of Henan University of Science and Technology from 2010 to 2013. All selected patients were not receiving chemotherapy and radiotherapy before surgery and identified by histopathologic in postoperative. The m RNA and protein expression levels of CHOP were determined in gastric cardia adenocarcinoma and matched adjacent normal tissues, using q RT-PCR, Western blot and immunohistochemical methods, and analyzed their relationship with malignant biological characteristics, such as clinical stages, tumor differentiation, lymph node metastasis and prognosis. SPSS17.0 software was used sample, P<0.05 was indicated statistical significance.Results1. q RT-PCR results showed that CHOPm RNA presents a low level of expression in GCA tissues, while significant expression in the corresponding non-cancerous adjacent cardiac tissue, there was a significant statistical significance between GCA and control group(P<0.01).2. Western blot results showed that CHOP protein density in the gastric cardia adenocarcinoma was significantly lower than that in corresponding non-cancerous adjacent cardiac tissue, the difference was significant statistical significance(P<0.01).3. Immunohistochemical results showed that CHOP positive expression in gastric cardia adenocarcinoma tissues was 54.4%(37/68), significantly lower than in corresponding adjacent non-cancerous tissues(82.4%, 56/68), the difference was statistically significant(P<0.01). CHOP positive expression rate in high, medium, poorly differentiated tissues were respectively: 93.3%, 47.8% and 40.0%, the difference was statistically significant(P<0.01). TNM staging, the positive rate of CHOP expression was: I ~ II of 80.0%, III of 47.2%(P<0.05). The positive expression of CHOP in lymph node metastasis group was 48.2% lower than that in without lymph node metastasis group(83.3%, P<0.05); while with the GCA patient’s gender, age were not related(P>0.05). Followed up months was 8 to 48 of 68 cases GCA patients, and the deadline is February 2014, which 40 cases of death and 28 cases of survival. The total survival rates of GCA patients in the 12 month, 36 month, 48 month were respectively: 77.7%, 53.3%, 32.6%.4. Correlation analysis was carried out on the q RT-PCR、Western blot and immunohistochemical result. The results show that they are significantly positive correlated. This indicate that CHOP m RNA levels were in line with protein expression.5. Kaplan-Meier survival analysis showed that lose of CHOP expression, differentiation lower, higher clinical stage and lymph node metastasis can be used as a survival predictors of GCA patients with lower survival rates(P<0.05). Cox proportional hazards regression model Univariate analysis showed that downregulation of the CHOP expression, lower degree of differentiation, higher TNM stage and lymph node metastasis can be used as an important predictor of poor prognosis in GCA patients(P<0.05). Multivariate analysis found that CHOP(RR=0.214, 95%CI 0.103-0.446, P=0.000) and TNM stage(RR=2.094, 95%CI 1.194-3.672, P=0.010) as effectively predict indicators in GCA patients with poor prognosis.Conclusion1. CHOP expression in gastric cardia adenocarcinoma was significantly lower than in matched adjacent normal tissues, which suggest that CHOP play an important role in the occurrence and development of gastric cardia adenocarcinoma.2. CHOP expression with the clinical stage of the increase, decrease histological grade and lymph node metastasis have closely related, but have not with gender and age factors in GCA, which suggest that CHOP may be associated with the invasion and metastasis of gastric cardia adenocarcinomainvasion.3. Survival was significantly decreased in GCA patients with missing CHOP expression, which suggest that down-regulation of CHOP can be used as a predictors of GCA patients with low survival rate; further multivariate analysis showed that the CHOP can be used as an independent prognostic factor in GCA patients.Key Words: ERS; CHOP; GCA; prognosis... |
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