Correlation Analysis Between Mortalin Overexpression And Clinicopathological Characteristics In Gastric Carcinoma

Background:Gastric Cancer(GC)is a common malignant tumor which occurs in the glandular epithelium of gastric mucosa.In recent years,the mortality of gastric cancer increased as the rapid growth of incidence.Although chemotherapy extend the life of patients with gastric cancer to some extent,it still need to improve the outcome of moderate advanced gastric cancer patients further.Some researches indicated that gastric cancer is caused by the interaction of multi-factors and genes.Hence,there is a great need for new biomarkers for early detection and prognostic evaluation of gastric cancer.Mortalin(also termed GRP75/mtHSP70/PBP74)is a member of the heat shock protein 70(HSP 70)family.It is encoded by the nuclear gene HSPA9B,which is localized on chromosome 5q31.1.1.Accumulating evidence has shown that Mortalin is elevated in many malignant tumors,such as intrahepatic cholangiocarcinoma,liver cancer,pancreatic cancer.Sun et al.found that Mortalin is highly expressed in non-small cell lung cancer,and correlated with high histological grades,advanced stages,and lymph node metastases of the patients with non-small cell lung cancer.Jin et al.demonstrated that Mortalin is upregulated in breast cancer and may be a useful poor prognostic biomarker as well as a potential therapeutic target for patients with breast cancer.In addition,the researchers proved that high expression of Mortalin can down-regulate the expression of E-cadherin,up-regulate the expression of snail and Vimentin,and promote the EMT process of tumor cells.All these findings indicated that Mortalin might be a new and independent predictor of prognosis in various tumors and can also be used to be a potential target for tumor therapy.However,there are relatively few published reports evaluating the role of Mortalin protein expression in GC.Objectives:To investigate the expression of Mortalin in GC cells and to determine its clinicopathological and prognostic significance.Materials and methods:The localization of Mortalin in SGC-7901 and MGC-803human gastric cancer cells were detected by immunofluorescence staining.EnVision immunohistochemistry was also used to detect Mortalin expression in well-defined tissues obtained from 111of GC,24 of gastric high grade intraepithelial neoplasia(HGIN),5 of gastric low grade intraepithelial neoplasia(LGIN)and 17 of gastric mucosa tissues.The correlations between overexpression of Mortalin and the clinical features of patients with GC were evaluated using chi-square test and Fisher’s exact tests.Results:1.Mortalin protein expression is increased in GC.IF staining indicated that the Mortalin protein exhibited a strictly cytoplasmic staining pattern in the SGC-7901 and MGC-803GC cells.IHC staining consistently demonstrated that the Mortalin protein positive rate was 91.0%(101/111)in the GC,which was significantly higher than that in the HGIN 66.7%(16/24),LGIN 60%(3/5)and the gastric mucosa tissues 0.0%(0/17;P<0.01).2.Mortalin overexpression was significantly correlated with poorly differentiation in GC.The rate of strongly positive Mortalin expression was significantly higher in the poorly diff.GC 89.1%(57/64)than in the moderately diff.72.5%(29/40)and well diff.GC 42.9%(3/7;P<0.05).Moreover,Mortalin overexpression was not related to patient gender,age and TNM stage of patients with GC(P>0.05).3.Mortalin is inversely correlated with the expression of P53,Ki-67 in GC.The positive and strongly positive rate of Mortalin protein was significantly higher in P53-positive GC 100.0%(77.5%)than in P53-negative cases(P<0.01).This result may indicate a positive correlation of P53 expression and Mortalin overexpression in GC.Mortalin protein overexpression was also significantly correlated with the increased expression of Ki-67.The positive and strong-positive rates of Mortalin were 97.4%and 76.9%in GC with higher Ki67 indexes.This result indicated that Mortalin is inversely correlated with the expression of P53,Ki-67 in GC,but not correlated with the expression of P16,HER2.Conclusions:1.Mortalin exhibited a primarily cytoplasmic staining pattern in the GC.Mortalin is significantly up-regulated in GC tissue samples and is associated with poorly differentiation of GC patients.2.Mortalin is inversely correlated with the expression of P53 and Ki-67 in GC and can potentially be used as a potential biomarker of prognostic evaluation and a molecular therapeutic target for patients of GC.