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目的探讨细胞外基质蛋白分子osteopontin(OPN)在非小细胞肺癌(NSCLC)中的表达状况及特点,以及其在肺癌发生演进中的作用及其临床意义。方法35例新鲜NSCLC肿瘤及其对照肺组织,采用逆转录PCR(RT-PCR)技术,分析OPN基因在RNA水平的表达改变。大样本石蜡包埋组织(662个有效样品的组织微阵列)以免疫组织化学染色,检测OPN蛋白在NSCLC中的表达状况,并分析其与肿瘤的组织学及临床特征的关系。结果RT-PCR分析显示,OPN在80.0%的NSCLC肿瘤组织中转录上调。免疫组化染色分析显示,OPN蛋白在肿瘤组织中的表达(59.6%)显著高于正常肺组织(25.2%,P<0.001),且OPN在鳞癌中的表达高于腺癌。通过对鳞癌的深入分析则表明,OPN蛋白表达水平在有淋巴结转移和无淋巴结转移的原发癌间有统计学意义(68.6%和49.7%,P= 0.001),而在同一组患者的原发癌和淋巴结转移癌之间的表达水平则趋于一致(68.6%和75.5%,P=0.171)。结论OPN在NSCLC(尤其是鳞癌)中表达水平明显升高,其过表达与肺鳞癌淋巴结转移密切相关,增加了肿瘤转移的风险(OR=2.212);OPN有促进肺癌恶性演进的作用。
Objective To investigate the expression of extracellular matrix protein (osteopontin) (OPN) in non-small cell lung cancer (NSCLC) and its characteristics and its role in the evolution of lung cancer and its clinical significance. Methods Twenty-five fresh NSCLC tumors and their control lung tissues were studied. Reverse transcription PCR (RT-PCR) was used to analyze the expression of OPN gene at RNA level. Large samples of paraffin-embedded tissue (662 valid samples of tissue microarray) were immunohistochemically stained to detect the expression of OPN protein in NSCLC and to analyze its relationship with the histological and clinical features of the tumor. Results RT-PCR analysis showed that OPN was upregulated in 80.0% of NSCLC tumor tissues. Immunohistochemical staining showed that the expression of OPN protein in tumor tissues (59.6%) was significantly higher than that in normal lung tissues (25.2%, P <0.001). The expression of OPN in squamous cell carcinoma was higher than that in adenocarcinoma. In-depth analysis of squamous cell carcinoma showed that the expression level of OPN protein was significantly different between primary cancer with lymph node metastasis and non-lymph node metastasis (68.6% and 49.7%, P = 0.001) The expression levels between cancers and lymph node metastases tended to be consistent (68.6% and 75.5%, P = 0.171). Conclusion The expression of OPN is significantly increased in NSCLC, especially in squamous cell carcinoma. The overexpression of OPN is closely related to lymph node metastasis of lung squamous cell carcinoma and increases the risk of tumor metastasis (OR = 2.212). OPN can promote the malignant progression of lung cancer.