Expression And Significance Of Heat Shock Protein 90α HSP90α) In Non-small Cell Lung Cancer

Objective:Lung cancer is the most common visceral malignancy around our world, non-small cell lung cancer (NSCLC) accounts for approximately 80% of all cases of lung cancer. Over 50% of patients with lung cancer at diagnosis have been the middle and advanced stage. Chemoradiotherapy is one of the effective modalities for middle and advanced NSCLC. Although multidepartment(MDT) therapy has been enhorced in clinical practice, 5-year survival rate of NSCLC is only about 15%. Clearly, the effection strategies are needed at the early diagnosis in lung cancer. Improve chemoradiosensitivity of lung carcinoma, and to increase local control rate and prolong survival is necessary. More and more studies showed that the oncogenesis, development and prognosis of lung cancer is the multiple course, including a lot of cancer-related genes. It had been proved that lowering the oxygenation of tissues made them more resistant to damage by ionizing for chemoradiation, and hypoxia in solid tumors not only decrease chemo-radiosensitivity but also leads to accelerate malignant progression and increase metastasis. With development of the molecular biology technology, it has been proved that the HSP90 and HIF-1αare high expression in various solid tumors, and they were closely related to the oncogenesis, development, tumor immune, multi-drug resistance and prognosis of the cancer patients.This study was to explore the expression of HSP90α, HIF-1αprotein and clinical significance in non-small cell lung cancer tissue specimens. Immunohistochemical method was used to investigated the expression of HSP90αand HIF-1αprotein. The relationship between HSP90αand HIF-1α, clinical pathological parameters and prognosis of NSCLC was analised. It was observed that the relationship of HSP90αand chemoradiation therapy efficacy, and provided theoretical and experimental basis for gene therapy new strategy of NSCLC, and approaches for NSCLC clinical therapy (especially individual therapy).Methods:1 50 cases specimens of NSCLC were collected from Novenber 2007 to October 2010, these patients diagnosed by biopsying with fiberbronchoscopy or percutaneous lung biopsy at the oncology department of Hebei people hospital.According to the TNM stage, the fifty cases were divided into two groups: earlier stage group(I-II, 10cases) and the mid-advanced stage group(III-IV, 40 cases). Including stage I: 0cases, stage II: 10cases, stage III: 20cases, stage IV: 20cases.2 Protein of HSP90αand HIF-1αin tissues of NSCLC were detected with immunohistochemistry, clinical-pathological parameters and prognostic factors were analied after therapy.3 Analyze the data with SPSS 13.0.Results:1 Expression of HSP90αin NSCLC:The immunohistochemical staining result of HSP90α: Expression of HSP90αprotein was observed in tissue of NSCLC, and the protein mainly expressed the cytoplasm, only a few in nuclei. In 50 NSCLC,the positive expression rates of HSP90αwas 78%(39/50). The results showed that the positive expression rate of HSP90αin I-II stage group and III-IV stage group were 40%(4/10) and 87.5%(35/40) respectively, and the positive expression rate of HSP90αin lymph node metastasis group and no-lymph node metastasis group were 87.8%(36/41) and 33.3%(3/9), respectively. Results of analysis showed that the expression of HSP90αin non-small cell lung cancer tissues was significantly correlated with lymph node metastasis and TNM stage(P<0.05). While there was no significance difference that the expression of HSP90αin some clinicopathologic parameters of NSCLC, such as gender, age, histological types, tumor locations, diameter of tumor, pathology type of tumor and tumor degree of differentiation. No statistical significant difference was found(P>0.05). 2 Expression of HIF-lαin NSCLC:The immunohistochemical staining result of HIF-lα, expression of HIF-lαprotein was observed in tissue of NSCLC, and the protein mainly expressed the nuclei, only a few in cytoplasm.In the 50 cases of NSCLC, the positive expression rates of HIF-lαwas 62%(31/50). The results showed that the expression of HIF-lαin III-IV stage group (72.5%(29/40)) was significantly higher than that in I-II stage group (20%(2/10)). The positive expression rate of HIF-lαin lymph node metastasis group and no-lymph node metastasis group were 70.7%(29/41) and22.2%(2/9) respectively. Results of analysis showed that the expression of HIF-lαin non-small cell lung cancer tissues was significantly correlated with lymph node metastasis and TNM stage(P<0.05). But it wasn't correlated with gender, age, histological types tumor locations, diameter of tumor, pathological type or tumor differentiation and tumor degree of differentiation. No statistical significant difference was found(P>0.05).3 The relationship between expression of HSP90αand HIF-1α:The co-expression of HSP90αand HIF-1αwas 30 cases in NSCLC, and 28 cases with NSCLC were mid-advanced stage, including stage III: 11cases, stage IV: 17cases.There was a close correlation between the expression of HSP90αand HIF-1αprotein in the non-small cell lung cancer tissues(Pearson coefficient of continency C=0.501, P=0.000).4 Analysis of survival rate in NSCLC after chemoradiotherapy:The one, two, three years survival rate of all patients was 42.9% and 18.8% and 8% after chemoradiotherapy, madian survive was 11.0 months, and mean survive was 15.4 months. The one, two, three years survival rate of patients with positive and negative expression of HSP90αwere 71.8%, 34.2%, 3.1% and 76.2%, 45.7%, 30.5%, respectively (P=0.009); The one, two, three years survival rate of patients with positive and negative expression of HIF-1αwere 64.2%, 7.7%, 3.9% and 64.7%, 40.4%, 16.2%, respectively (P=0.015).5 The prognosis and influential factors analysis in NSCLC:Analysis with one-way: Clinical stage, lymph nodes metastasis, HSP90αand HIF-1αwere correlated with prognosis of NSCLC after chemor adi-otherapy (P<0.05). But it wasn't correlated with gender, age, histological types tumor locations,diameter of tumor, pathological type or tumordifferentiation and tumor degree of differentiation(P>0.05).Analysis with Multi-way: Analysis of Cox multivariate showed that TNM stage (B=1.925,P=0.002) and HIF-1α(B=0.834,P=0.030) were related with prognosis of NSCLC.They are the independent prognostic factor of NSCLC. While lymph nodes metastasis and HSP90αhad been not detected to the Cox regression modle(P>0.05).Conclusion:1 HSP90αand HIF-1αhad high expressions in non-small cell lung cancer tissues. The expressions of HSP90αand HIF-1αprotein in NSCLC tissues were significantly correlated with lymph node metastasis and TNM stage, which was correlated with clinical stages.2 There was a close correlation between the expression of HSP90αand HIF-1αprotein in the non-small cell lung cancer tissues.3 The survival rate of the negative expression of HSP90αand HIF-1αwas significantly higher than positive obviously of NSCLC.4 Clinical stage, lymph nodes metastasis, HSP90αand HIF-1αwere correlated with prognosis of NSCLC after chemoradiotherpy. The clinical stage and HIF-1αwere the independent prognostic factors of NSCLC.