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医学论文范文:肺耐药相关蛋白表达与非小细胞肺癌血管生成的相关性
【摘要】 目的 探讨肺耐药相关蛋白(LRP)、血管内皮生长因子(VEGF)及微血管密度(MVD)在非小细胞肺癌(NSCLC)中的变化、相互关系及可能的机制。方法 应用免疫组化技术检测56例NSCLC癌组织和27例正常对照肺组织中LRP、VEGF表达及MVD情况。结果 ①LRP阳性表达分布于癌细胞胞浆内，表达率66.1%，显著高于对照肺组织(P<0.01)，其显著性与病理类型无关;NSCLC组LRP的表达在不同性别、TNM分期、有无淋巴结转移及两年生存率的比较上均无明显统计学意义(P>0.05)。②与对照组比较，NSCLC组VEGF表达明显升高(P<0.01)，其显著性与病理类型无关。NSCLC组VEGF表达与TNM分期、有无淋巴结转移相关(P<0.05)。③NSCLC组MVD明显高于对照组(P<0.01)，其显著性不受病理类型、病理分级的影响。MVD在Ⅲ+Ⅳ期肺癌中为18.5±5.8，明显高于Ⅰ期的13.8±5.1(P<0.05)，有淋巴结转移的高于无淋巴结转移者(P<0.05)，两年存活的MVD低于两年死亡的MVD(P<0.01)。④NSCLC组VEGF、LRP高表达和MVD增高具有一致性(P<0.05)。结论 非小细胞肺癌血管生成与肺耐药相关基因具有一定的相关性。LRP的高表达可能与VEGF上调其基因及VEGF促进肿瘤MVD增加有关。抑制肿瘤新生血管的生成有望降低甚或遏制对非小细胞肺癌化疗的耐药性。
【关键词】 非小细胞肺癌;肺耐药相关蛋白;血管生成;免疫组化
Correlation between expression of lung resistance-related protein and angiogenesis in non-small cell lung cancerWEI Xiao-hong, MA Ai-qun, SHAO Jie, YANG Lan, CHEN Ming-wei, WANG Jun-huiDepartment of Respiratory Medicine, the First Affiliated Hospital, Medical School ofXian Jiaotong University, Xian 710061; Department of Cardiovascular Medicine,the First Affiliated Hospital, Medical School of Xian Jiaotong University, Xian 710061;Department of Internal Medicine, No. 521 Hospital of Xian, Xian 710061, ChinaABSTRACT: Objective To investigate the changes in lung resistance-related protein (LRP) and vascular endothelial growth factor (VEGF) expressions and micro-vessel density (MVD) in non-small cell lung cancer (NSCLC), and to elucidate their possible relationship and mechanism. Methods Immunohistochemistry was used to detect changes in LRP and VEGF expressions, and MVD level in lung tissues of 56 NSCLC cases and 27 normal controls. Results ① LRP expression (66.1%) was concentrated in the cytoplasm of cancer cells, which was significantly higher than that in lung tissues of control group (P<0.01); the significance was not related to the pathological type. There was no significant difference in LRP expression among gender, TNM stage, lymph node metastasis, and two-year survival in NSCLC (P>0.05). ② In comparison to the control group, NSCLC group had significantly increased VEGF expression (P<0.01), which was not related to the pathological type. VEGF expression in NSCLC group had a significant association with TNM stage and lymph node metastasis (P<0.05). ③ The NSCLC group had a significantly higher MVD than the control group (P<0.01), which was not affected by the pathological type or degree. MVD value (18.5±5.8) of stage Ⅲ and Ⅳ in NSCLC group was significantly higher than that (13.8±5.1) of stage Ⅰ (P<0.05); MVD value for patients with lymph node metastasis was higher than that without lymph node metastasis (P<0.05); MVD value for patients with two-year survival was less than those who died within two years (P<0.01). ④ NSCLC group with high VEGF and LRP expressions had a consistently increased MVD value (P<0.05). Conclusion There is a certain relationship between tumor angiogenesis and LRP expression in NSCLC. VEGF is responsible for the high expression of LRP through up-regulating LRP gene and augmenting tumor MVD. Inhibition of angiogenesis in tumor is expected to reduce or inhibit drug resistance to NSCLC.
KEY WORDS: non-small cell lung cancer (NSCLC); lung resistance-related protein (LRP); angiogenesis; immunohistochemistry
肿瘤细胞对化疗药物医.学全.在.线网站www.med126.com产生原发或继发耐药是化疗失败的主要原因之一。非小细胞肺癌(non-small cell lung cancer, NSCLC)耐药是多因素、多基因参与的过程，不仅与耐药相关基因及其编码蛋白过度表达有关，亦可能涉及肿瘤的血管生成[1]。因此，探讨耐药相关蛋白和血管生成的关系将有助于了解其耐药机制并为进一步研究逆转耐药提供理论基础。本研究采用免疫组化技术检测NSCLC组织中肺耐药相关蛋白(lung resistance-related protein, LRP)、血管内皮生长因子(vascular endothelial growth factor, VEGF)的表达及微血管密度(micro-vascular density, MVD)，并探讨它们之间的关系，现报告如下。
1 材料与方法
