| Lung cancer is one of the most malignant cancers threatening people's health and life, and it's is also one of the most rapid increasing cancer both in morbidity and mortality .The death caused by lung cancer account for 33% of total malignant death in male and 25% in female. The epidemiology investigation showed that the morbidity and mortality of it is remaining increasing in recent years. In the past three decades , though the surgical technique and multi-modality therapy have progressed greatly , but the over all cure rate of lung cancer is still only 10%~15%.The main causes of this was due to lack of effective approaches for early diagnosis and useful methods to manage the metastasis of this disease. Eighty per cent of lung cancer patients had reached advanced stage when diagnosed and had a bad prognosis. While the five-years survival rates of stage I disease was over 80%.So the key measures to increasing the survival rates and to decreasing the mortality of it is still early diagnosis and early management. The oncogenesis , development invasion and metastasis of lung cancer is acomplex course of multisteps and multiprocedures.The natural history of lung cancer is 20-30 years from normal cell transformating to precancerous lesions, carcinoma in site, progressive stage until to death. The long-term progressive features of lung cancer made it possible to make early diagnosis and early management .However ,due to lack of effective early diagnosis method,so only about 2% to 3% cases of lung cancer patients could get early diagnosis.Recent years studies have showed that the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B 1) was o verexpression in the early stages of lung cancer and precancerous lesions and it can be detected by sputum cytology.This rises the interest to investigate the relationship between hnRNPA2/Bl expression and lung cancer. In order to explore the difference of hnRNPA2/Bl expression in different lung tissues ,the relationship between the hnRNPA2/Bl expression and the clinical pathophysiological characteristics of lung cancer ,also to investigate the possibility of determing hnRNPA2/Bl expression to make early diagnosis of lung cancer and its clinical significance , in this study we systematically detected the protein and mRNA expression level of hnRNPA2/Bl in 58 cases of NSCLC tissues, the adjacent non-cancerous tissues and 30 cases of benign pulmonary lesions tissues by Immunohistochemistry and RT —PCR methods.The expression level of hnRNPA2/Bl protein in normal or hyperplastic bronchial epithelium of resected stumps in patients with lung cancer were detected at the same time. The results showed as follows:1. The expression level of hnRNPA2/Bl protein in lung cancer tissue (3.3793 ± 2.1095) was significantly higher than that in the adjacentnon-cancerous lung tissue (2.0862 + 1.3801) and the benign pulmonary lesions tissue (1.2333 + 1.1651) respectively (P<0.001) . The same result was found between the adjacent non-cancerous lung and the benign pulmonary lesion group (/><0.05) . The expression level of hnRNPA2/Bl protein in hyperplastic bronchial epithelium of resected stumps in patients with lung cancer (2.5200 ±2.0232) was significantly higher than that in normal bronchial epithelium (1.3939+1.1440) (P<0.05) .2. The expression level of hnRNPA2/Bl protein in T3+T4 lung cancer tissue (4.2903 + 1.7165) was significantly higher than that in T1+T2 lung cancer tissue (2.2222 + 2.1543) (P<0.001) . The expression level of hnRNPA2/Bl protein in lung cancer tissue with lymph node metastasis (4.2813 ±1.8003) was significantly higher than that in lung cancer tissue without lymph node metastasis (2.1538±2.0531) (F<0.001) . The expression level of hnRNPA2/Bl protein in poor differentiated lung cancer tissue (4.1875 ±1.7122) was significantly higher than that in moderate-well differentiated lung cancer tissue (2.2692 ± 2.1549) (P < 0.01). The expression level of hnRNPA2/Bl protein in stage III + IV disease (4.7143 + 1.3294) was significantly higher than that in stage I +11 disease(2.0333 ±2.0254) (/)<0.001). The expression level of hnRNPA2/Bl protein in squamous cell carcinoma, adenocarcinoma , adenosquamous cell carcinoma was 2.8333 + 2.0934, 3.4516 ±2.4061 and 3.8889 ± 1.3642 respectively .There was no significant difference among different histological classification (P>0.05).3. The positive expressive rates of hnRNPA2/Bl mRNA in lung cancer tissue, the adjacent non-cancerous lung tissue and the benignpulmonary lesion tissue were 79.31%(46/58), 58.62%(34/58) and 33.33%(10/30) respectively. Both hnRNPA2 and hnRNPBl mRNA expressed in the positive lung cancer tissue. In positive adjacent non-cancerous lung tissue, 38.24%(13/34) cases expressed both hnRNPA2 and hnRNPBl mRNA, while the remaining 61.76%(21/34) cases only expressed hnRNPA2 mRNA. The positive benign pulmonary lesion tissue only expressed hnRNPA2 mRNA.4. The expression level of hnRNPA2/Bl mRNA in non- small cell lung cancer tissue (0.6940+0.3615) was significantly higher than that in the adjacent non-cancerous lung tissue (0.4343 + 0.3578) and the benign pulmonary lesion tissue (0.2000+0.1392) (P<0.001). The expression level of hnRNPA2/Bl mRNA in the adjacent non-cancerous lung was also remarkably higher than that in the benign pulmonary diseases group (P< 0.01) .5. The expression level of hnRNPA2/Bl mRNA in T3+T4 lung cancer tissue (0.8084+0.2745) was significantly higher than that in Tl +T2 lung cancer tissue (0.5626+0.4075) (P<0.05) .The expression level of hnRNPA2/Bl mRNA in lung cancer tissue with lymph node involvement (0.7881 +0.3065) was significantly higher than that in without lymph node involvement (0.5781+0.3952 ) (P<0.05) . The expression level of hnRNPA2/Bl mRNA in poor differentiated lung cancer (0.8009+0.2663), was significantly higher than that in moderate-well differentiated lung cancer tissue (0.5623 + 0.4212) (P < 0.05). The expression level of hnRNPA2/Bl mRNA in stage III + IV disease (0.8175 + 0.2916) was significantly higher than that in stage I + II disease (0.5787+0.3863) (P<0.05). The expression level of hnRNPA2/Bl mRNA in squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma was 0.6744 + 0.3756, 0.6529+0.3945 and 0.8744 ±0.0627 respectively. There was no significant difference among the different histological classification of the cancer (P>0.05).6. The expression level of hnRNPA2/Bl protein and mRNA are correlated significantly (P<0.001). The expression level of hnRNPA2/B 1 protein and mRNA in the lung cancer tissue had a significant positive correlations with the size of primary cancer, the lymph node metastasis status , the P—TNM stages while it had a significant negative correlations with the grade of cell differentiation CP< 0.05) .But it had no significant correlations with the sex , age , smoking history, location of primary cancer and histological classification (P>0.05) .Conclusions (1) An increasing tendence of hnRNPA2/B 1 protein and mRNA was existed from benign pulmonary tissue to the adjacent non-cancerous lung tissue, hyperplastic bronchial epithelium and the lung cancer tissue. There was an overexpression of hnRNPA2/Bl in the lung cancer tissue, the adjacent non-cancerous lung tissue and the hyperplastic bronchial epithelium. (2) The expression level of hnRNPA2/Bl protein and mRNA in the lung cancer tissue had a significant positive correlations with the size of primary cancer, the lymph node metastasis status and the P— TNM stages while it had a significant negative correlations with the grade of cell differentiation. However, it had no significants correlation with the sex, age, smoking, location of primary cancer and histological classification. (3)The overexpression of hnRNPA2/Bl was related to the oncogenesis,development and lymph nodes metastasis of NSCLC and the expression level was increasing with the progression of lung cancer. (4)To detect the expression of hnRNPA2/Bl may be helpful to the early diagnosis ,prediction of the progression of lung cancer and to guidance of multimodality therapy of lung cancer.
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