The Expression And Clinical Significance Of ALDH1,HSP60 And MMP-9 In Gastric Cancer

Objective: The aim of this study is to investigate the expression of ALDH1, HSP60 and MMP-9 in gastric cancer, and demonstrate the relationship of ALDH1 and HSP60 expression with clinicopathologic parameters and prognosis in gastric cancer.Methods: Gastric carcinoma tissues were obtained from gastrectomy specimens of 223 patients from the department of general surgery, the Affiliated Hospital of Guilin Medical University(Guilin, China) between January 2005 and December 2008. All the gastric cancer patients enrolled in this study had a histologically confirmed diagnosis which was pathologically confirmed after surgery. The clinical data of gastric cancer patients contains tumor site, tumor size, grade of differentiation, depth invasion, lymph node metastasis, stage of disease, recurrence-free survival and overall survival. ALDH1, HSP60 and MMP-9 was evaluated by immunohistochemistry in 223 gastric carcinomasamples. The association between expression of ALDH1/HSP60 and MMP-9,clinicopathological parameters and prognosis of gastric cancer was examined.Results: There were 223 specimens of gastric carcinoma who were evaluated by immunohistochemistry. ALDH1, HSP60 and MMP-9 staining mainly located in cytoplasm of tumor cells. The positive rates of ALDH1,HSP60 and MMP-9 were 50%、58.3% and 47.1%, respectively.According to the results of immunohistochemistry, we associated the ALDH1 expression with clinicopathologic parameters in gastric cancer. ALDH1 protein expression was significantly associated with depth invasion(P < 0.001),lymph node metastasis(P < 0.001) and stage of disease(P < 0.001). No significant association was observed between gender, age, tumor size, tumor site and grade of differentiation with ALDH1 expression. The univariate analyses showed that the patients with ALDH1-positive expression had a significant lower overall survival and recurrence-free survival than those with ALDH1-negative expression. And the multivariate analyses revealed that ALDH1 was an independent prognostic factor for both overall survival and recurrence-free survival(both P < 0.001). Furthermore, ALDH1 overexpression was associated with poor prognosis in patients subgroups stratified by tumor size, depth invasion and lymph node metastasis. Moreover, ALDH1 was significantly correlated with MMP-9 in gastric cancer tissues(P < 0.001).Patients who had ALDH1 overexpression, in which tumor cells displayed highinvasiveness, had poor OS and shorter RFS.The level of HSP60 protein was significantly associated with depth invasion, lymph node metastasis and stage of disease(all P < 0.05), while no significant association was observed between gender, age, tumor size, tumor site and grade of differentiation with HSP60 expression. Both univariate and multivariate analyses revealed that HSP60 was an independent prognostic factor for both overall survival and recurrence-free survival(both P < 0.05).Furthermore, HSP60 overexpression was associated with a poor prognosis in patients with advanced gastric cancer in different risk groups. Moreover, HSP60 was significantly correlated with MMP-9 among 223 gastric cancer tissues(P <0.001). Patients who had HSP60 overexpression, in which tumor cells displayed high invasiveness, had poor OS and shorter RFS.Conclusion: ALDH1 and HSP60 are overexpressed and associated with aggressiveness in gastric cancer. ALDH1 and HSP60 play an important role on tumor prognosis, and may act as a promising target for prognostic prediction.