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醫(yī)學(xué)論文范文:肺耐藥相關(guān)蛋白表達(dá)與非小細(xì)胞肺癌血管生成的相關(guān)性
【摘要】 目的 探討肺耐藥相關(guān)蛋白(LRP)、血管內(nèi)皮生長(zhǎng)因子(VEGF)及微血管密度(MVD)在非小細(xì)胞肺癌(NSCLC)中的變化、相互關(guān)系及可能的機(jī)制。方法 應(yīng)用免疫組化技術(shù)檢測(cè)56例NSCLC癌組織和27例正常對(duì)照肺組織中LRP、VEGF表達(dá)及MVD情況。結(jié)果 ①LRP陽性表達(dá)分布于癌細(xì)胞胞漿內(nèi)，表達(dá)率66.1%，顯著高于對(duì)照肺組織(P<0.01)，其顯著性與病理類型無關(guān);NSCLC組LRP的表達(dá)在不同性別、TNM分期、有無淋巴結(jié)轉(zhuǎn)移及兩年生存率的比較上均無明顯統(tǒng)計(jì)學(xué)意義(P>0.05)。②與對(duì)照組比較，NSCLC組VEGF表達(dá)明顯升高(P<0.01)，其顯著性與病理類型無關(guān)。NSCLC組VEGF表達(dá)與TNM分期、有無淋巴結(jié)轉(zhuǎn)移相關(guān)(P<0.05)。③NSCLC組MVD明顯高于對(duì)照組(P<0.01)，其顯著性不受病理類型、病理分級(jí)的影響。MVD在Ⅲ+Ⅳ期肺癌中為18.5±5.8，明顯高于Ⅰ期的13.8±5.1(P<0.05)，有淋巴結(jié)轉(zhuǎn)移的高于無淋巴結(jié)轉(zhuǎn)移者(P<0.05)，兩年存活的MVD低于兩年死亡的MVD(P<0.01)。④NSCLC組VEGF、LRP高表達(dá)和MVD增高具有一致性(P<0.05)。結(jié)論 非小細(xì)胞肺癌血管生成與肺耐藥相關(guān)基因具有一定的相關(guān)性。LRP的高表達(dá)可能與VEGF上調(diào)其基因及VEGF促進(jìn)腫瘤MVD增加有關(guān)。抑制腫瘤新生血管的生成有望降低甚或遏制對(duì)非小細(xì)胞肺癌化療的耐藥性。
【關(guān)鍵詞】 非小細(xì)胞肺癌;肺耐藥相關(guān)蛋白;血管生成;免疫組化
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
腫瘤細(xì)胞對(duì)化療藥物醫(yī).學(xué)全.在.線網(wǎng)站zxtf.net.cn產(chǎn)生原發(fā)或繼發(fā)耐藥是化療失敗的主要原因之一。非小細(xì)胞肺癌(non-small cell lung cancer, NSCLC)耐藥是多因素、多基因參與的過程，不僅與耐藥相關(guān)基因及其編碼蛋白過度表達(dá)有關(guān)，亦可能涉及腫瘤的血管生成[1]。因此，探討耐藥相關(guān)蛋白和血管生成的關(guān)系將有助于了解其耐藥機(jī)制并為進(jìn)一步研究逆轉(zhuǎn)耐藥提供理論基礎(chǔ)。本研究采用免疫組化技術(shù)檢測(cè)NSCLC組織中肺耐藥相關(guān)蛋白(lung resistance-related protein, LRP)、血管內(nèi)皮生長(zhǎng)因子(vascular endothelial growth factor, VEGF)的表達(dá)及微血管密度(micro-vascular density, MVD)，并探討它們之間的關(guān)系，現(xiàn)報(bào)告如下。
1 材料與方法
