非小细胞肺癌组织IGF-1R和HIF-1α表达临床意义探讨
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摘要
目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)组织胰岛素样生长因子1受体(insulin-like growth factor 1receptor,IGF-1R)和乏氧诱导因子1α(anoxic inducible factor 1α,HIF-1α)表达与临床病理因素及无病生存率(disease-free survival,DFS)的相关性。方法采用免疫组织化学法检测54例手术切除的NSCLC组织和20例癌旁组织中IGF-1R和HIF-1α表达,运用统计学方法分析两者间的相关性,结合临床病理特点对其复发情况进行分析。结果 NSCLC组织中IGF-1R和HIF-1α阳性表达率分别为62.96%(34/54)和57.41%(31/54),显著高于癌旁组织的15.00%(3/20)和20.00%(4/20),差异有统计学意义(χ~2=13.430,P=0.010;χ~2=8.193,P=0.040)。IGF-1R阳性表达与分化程度(χ~2=5.082,P=0.024)和淋巴结转移(χ~2=6.480,P=0.011)相关;HIF-1α阳性表达与临床分期(χ~2=9.891,P=0.002)、分化程度(χ~2=6.312,P=0.012)和淋巴结转移(χ~2=5.035,P=0.025)相关。IGF-1R和HIF-1α表达呈正相关,r=0.465,P<0.001。单因素分析显示,IGF-1R和HIF-1α阳性表达是患者1年DFS的危险因素(χ~2=6.392,P=0.011;χ~2=10.596,P=0.001)。多因素分析结果显示,HIF-1α(HR=3.649,95%CI:1.598~8.346,P=0.02)为1年DFS独立危险因素。结论 NSCLC组织IGF-1R和HIF-1α表达呈正相关性,提示在NSCLC发生发展过程中可能存在协同作用,两者联合检测可能会成为判断NSCLC复发转移的指标,并为临床分子靶向治疗研究提供参考。
OBJECTIVE To explore the relations between IGF-1 Rand HIF-1αin non-small cell lung cancer tissues and pathological factors and DFS.METHODS The immunohistochemical method was used to detect the expression of IGF-1 Rand HIF-1αin 54 patients with non-small cell lung cancer and 20 cases of adjacent tissues,and statistical methods were used to analyze the correlation between IGF-1 Rand HIF-1α.RESULTS The positive expression rate of IGF-1 Rand HIF-1αin the NSCLC tissues was significantly higher than that of the adjacent tissues(χ~2=13.430,P=0.010;χ~2=8.193,P=0.040).The positive expression rate of IGF-1 R was related to differentiation(χ~2=5.082,P=0.024)and lymph node metastasis(χ~2=6.480,P=0.011).The positive expression rate of HIF-1αwas related to clinical stages(χ~2=9.891,P=0.002),differentiated degree(χ~2=6.312,P=0.012),and lymph node metastasis(χ~2=5.035,P=0.025).IGF-1 Rexpression was positively correlated to HIF-1αexpression in NSCLC(r=0.465,P<0.001).Single factor analysis results showed the positive expression of IGF-1 Rand HIF-1αwas a risk factor for patients with DFS for 1 year(χ~2=6.392,P=0.011;χ~2=10.596,P=0.001).Multi-factor analysis results showed HIF-1(HR=3.649,95%CI:1.598-8.346,P=0.02)was the independent risk factor of DFS for 1 year.CONCLUSION IGF-1 Rexpression is positively correlated to HIF-1αexpression in NSCLC,which suggests that there may be synergistic effect in the development of NSCLC,and the combined detection may become an indicator of the recurrence and metastasis of NSCLC,and provide reference for clinical molecular targeted therapy.
OBJECTIVE To explore the relations between IGF-1 Rand HIF-1αin non-small cell lung cancer tissues and pathological factors and DFS.METHODS The immunohistochemical method was used to detect the expression of IGF-1 Rand HIF-1αin 54 patients with non-small cell lung cancer and 20 cases of adjacent tissues,and statistical methods were used to analyze the correlation between IGF-1 Rand HIF-1α.RESULTS The positive expression rate of IGF-1 Rand HIF-1αin the NSCLC tissues was significantly higher than that of the adjacent tissues(χ~2=13.430,P=0.010;χ~2=8.193,P=0.040).The positive expression rate of IGF-1 R was related to differentiation(χ~2=5.082,P=0.024)and lymph node metastasis(χ~2=6.480,P=0.011).The positive expression rate of HIF-1αwas related to clinical stages(χ~2=9.891,P=0.002),differentiated degree(χ~2=6.312,P=0.012),and lymph node metastasis(χ~2=5.035,P=0.025).IGF-1 Rexpression was positively correlated to HIF-1αexpression in NSCLC(r=0.465,P<0.001).Single factor analysis results showed the positive expression of IGF-1 Rand HIF-1αwas a risk factor for patients with DFS for 1 year(χ~2=6.392,P=0.011;χ~2=10.596,P=0.001).Multi-factor analysis results showed HIF-1(HR=3.649,95%CI:1.598-8.346,P=0.02)was the independent risk factor of DFS for 1 year.CONCLUSION IGF-1 Rexpression is positively correlated to HIF-1αexpression in NSCLC,which suggests that there may be synergistic effect in the development of NSCLC,and the combined detection may become an indicator of the recurrence and metastasis of NSCLC,and provide reference for clinical molecular targeted therapy.
引文
[1]容宇,郝雁冰,陈万生,等.Ⅰ/Ⅱ期非小细胞肺癌患者微创手术的近远期效果研究[J].实用癌症杂志,2015,31(8):1160-1162.
[2]Aisner DL,Marshall CB.Molecular pathology of non-small cell lung cancer:a practical guide[J].Am J Clin Pathol,2012,138(3):332-346.
[3]Desbois-Mouthon C,Baron A,Blivet-Van EMJ,et al.Insulin-like growth factor-1receptor inhibition induces a resistance mechanism via the epidermal growth factor receptor/HER3/AKT signaling pathway:rational basis for cotargeting insulin-like growth factor-1receptor and epidermal growth factor receptor in hepatocellular carcinoma[J].Clin Cancer Res,2009,15(17):5445-5456.
[4]余梦懿,成元华,申九妹,等.肝细胞癌中胰岛素样生长因子1受体及血管内皮生长因子的表达及意义[J].贵州医药,2015,39(9):776-778.
[5]Rosenzweig SA,Atreya HS.Defining the pathway to insulin-like growth factor system targeting in cancer[J].Biochem Pharmacol,2010,80(8):1115-1124.
[6]Martin JL,Baxter RC.Signalling pathways of insulin-like growth factors(IGFs)and IGF binding protein-3[J].Growth Factors,2011,29(6):235-244.
[7]Kim JS,Kim ES,Liu D,et al.Prognostic impact of insulin receptor expression on survival of patients with non small cell lung cancer[J].Cancer,2012,118(9):2454-2465.
[8]Fu S,Tang H,Liao Y,et al.Expression and clinical significance of insulin-like growth factor 1in lung cancer tissues and perioperative circulation from patients with non-small-cell lung cancer[J].Curr Oncol,2016,23(1):12-19.
[9]Zhao S,Qiu Z,He J,et al.Insulin-like growth factor receptor 1(IGF1R)expression and survival in non-small cell lung cancer patients:a meta-analysis[J].Int J Clin Exp Pathol,2014,7(10):6694-6704.
[10]盖领,茅国新,沈浮,等.IGF-1R在非小细胞肺癌中的表达及其临床意义[J].肿瘤学杂志,2015,21(7):542-545.
[11]Keith B,Johnson RS,Simon MC.HIF1αand HIF2α:sibling rivalry in hypoxic tumour growth and progression[J].Nat Rev Cancer,2011,12(1):9-22.
[12]栗军香,呼金田,耿静,等.HIF-1α、VEGF在子宫内膜癌中的表达及其与肿瘤血管生成的关系[J].海南医学,2016,27(23):3828-3831.
[13]高磊,胡扬喜,尹宁伟,等.大肠癌组织转化生长因子-β1、缺氧诱导因子-1α和血管内皮生长因子的表达及其临床意义[J].中国老年学杂志,2016,36(12):2953-2955.
[14]潘广晔,张作峰,王刚平.HIF-1α和Survivin在乳腺癌中的表达及意义[J].中国临床实用医学,2016,7(1):20-23.
[15]Li C,Lu HJ,Na FF,et al.Prognostic role of hypoxic inducible factor expression in non-small cell lung cancer:a meta-analysis[J].Asian Pac J Cancer Prev,2013,14(6):3607-3612.
[16]杨常建,董海林,聂改红,等.HIF-1α与VEGF在非小细胞肺癌组织中的表达及临床意义[J].临床医学,2016,39(6):35-36.
[17]巩晓瑞.EGFR-TKI耐药的分子机制及耐药后治疗策略[J].癌症进展,2014,12(2):134-139.
[18]Yeo CD,Park KH,Park CK,et al.Expression of insulin-like growth factor 1receptor(IGF-1R)predicts poor responses to epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors in nonsmall cell lung cancer patients harboring activating EGFR mutations[J].Lung Cancer,2015,87(3):311-317.
[19]王津京,张为民,陈蓓,等.上皮-间质转化和胰岛素样生长因子Ⅰ型受体在非小细胞肺癌EGFR-TKIs获得性耐药中的作用[J].肿瘤,2013,33(2):103-110.
[20]Morgillo F,Della Corte CM,Fasano M,et al.Mechanisms of resistance to EGFR-targeted drugs:lung cancer[J].ESMO Open,2016,1(3):e000060.
[21]覃玲艳,王华新,郭凌川,等.CD147、EGFR和HIF-1α在非小细胞肺癌中的表达及意义[J].江苏医药,2016,42(4):423-427.
[2]Aisner DL,Marshall CB.Molecular pathology of non-small cell lung cancer:a practical guide[J].Am J Clin Pathol,2012,138(3):332-346.
[3]Desbois-Mouthon C,Baron A,Blivet-Van EMJ,et al.Insulin-like growth factor-1receptor inhibition induces a resistance mechanism via the epidermal growth factor receptor/HER3/AKT signaling pathway:rational basis for cotargeting insulin-like growth factor-1receptor and epidermal growth factor receptor in hepatocellular carcinoma[J].Clin Cancer Res,2009,15(17):5445-5456.
[4]余梦懿,成元华,申九妹,等.肝细胞癌中胰岛素样生长因子1受体及血管内皮生长因子的表达及意义[J].贵州医药,2015,39(9):776-778.
[5]Rosenzweig SA,Atreya HS.Defining the pathway to insulin-like growth factor system targeting in cancer[J].Biochem Pharmacol,2010,80(8):1115-1124.
[6]Martin JL,Baxter RC.Signalling pathways of insulin-like growth factors(IGFs)and IGF binding protein-3[J].Growth Factors,2011,29(6):235-244.
[7]Kim JS,Kim ES,Liu D,et al.Prognostic impact of insulin receptor expression on survival of patients with non small cell lung cancer[J].Cancer,2012,118(9):2454-2465.
[8]Fu S,Tang H,Liao Y,et al.Expression and clinical significance of insulin-like growth factor 1in lung cancer tissues and perioperative circulation from patients with non-small-cell lung cancer[J].Curr Oncol,2016,23(1):12-19.
[9]Zhao S,Qiu Z,He J,et al.Insulin-like growth factor receptor 1(IGF1R)expression and survival in non-small cell lung cancer patients:a meta-analysis[J].Int J Clin Exp Pathol,2014,7(10):6694-6704.
[10]盖领,茅国新,沈浮,等.IGF-1R在非小细胞肺癌中的表达及其临床意义[J].肿瘤学杂志,2015,21(7):542-545.
[11]Keith B,Johnson RS,Simon MC.HIF1αand HIF2α:sibling rivalry in hypoxic tumour growth and progression[J].Nat Rev Cancer,2011,12(1):9-22.
[12]栗军香,呼金田,耿静,等.HIF-1α、VEGF在子宫内膜癌中的表达及其与肿瘤血管生成的关系[J].海南医学,2016,27(23):3828-3831.
[13]高磊,胡扬喜,尹宁伟,等.大肠癌组织转化生长因子-β1、缺氧诱导因子-1α和血管内皮生长因子的表达及其临床意义[J].中国老年学杂志,2016,36(12):2953-2955.
[14]潘广晔,张作峰,王刚平.HIF-1α和Survivin在乳腺癌中的表达及意义[J].中国临床实用医学,2016,7(1):20-23.
[15]Li C,Lu HJ,Na FF,et al.Prognostic role of hypoxic inducible factor expression in non-small cell lung cancer:a meta-analysis[J].Asian Pac J Cancer Prev,2013,14(6):3607-3612.
[16]杨常建,董海林,聂改红,等.HIF-1α与VEGF在非小细胞肺癌组织中的表达及临床意义[J].临床医学,2016,39(6):35-36.
[17]巩晓瑞.EGFR-TKI耐药的分子机制及耐药后治疗策略[J].癌症进展,2014,12(2):134-139.
[18]Yeo CD,Park KH,Park CK,et al.Expression of insulin-like growth factor 1receptor(IGF-1R)predicts poor responses to epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors in nonsmall cell lung cancer patients harboring activating EGFR mutations[J].Lung Cancer,2015,87(3):311-317.
[19]王津京,张为民,陈蓓,等.上皮-间质转化和胰岛素样生长因子Ⅰ型受体在非小细胞肺癌EGFR-TKIs获得性耐药中的作用[J].肿瘤,2013,33(2):103-110.
[20]Morgillo F,Della Corte CM,Fasano M,et al.Mechanisms of resistance to EGFR-targeted drugs:lung cancer[J].ESMO Open,2016,1(3):e000060.
[21]覃玲艳,王华新,郭凌川,等.CD147、EGFR和HIF-1α在非小细胞肺癌中的表达及意义[J].江苏医药,2016,42(4):423-427.