Ⅰ期非小细胞肺癌组织血管内皮生长因子C、细胞角蛋白19表达与患者预后的相关性
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摘要
目的:分析Ⅰ期非小细胞肺癌(NSCLC)组织血管内皮生长因子C(VEGF-C)、细胞角蛋白19(CK19)水平的变化,并探讨其与患者预后的相关性。方法:采用免疫组化检测肺癌组织中VEGF-C、CK19蛋白的表达,分析其与肺癌患者临床病理特点的相关性。随访至少3年,采用Kaplan-Meier法分析不同VEGF-C、CK19蛋白表达患者术后复发及疾病进展时间的差异。结果:VEGF-C和CK19在不同分化程度、胸膜侵犯患者肺癌组织中的表达比较差异均有统计学意义(P<0.05)。VEGF-C表达与CK19表达呈显著正相关(r=0.483,P<0.05)。术后3年,VEGF-C和CK19阳性患者复发率均显著高于VEGF-C和CK19阴性患者(x~2=14.16, 17.25,P<0.05)。Kaplan-Meier法显示VEGF-C阳性、阴性者中位TTP分别为29.2个月(95%CI:27.5～30.9)、36.2个月(95%CI:35.0～37.5);CK19阳性、阴性者中位TTP分别为28.4个月(95%CI:26.6～30.2)、37.8个月(95%CI:36.4～39.1)。VEGF-C、CK19阴性者与阳性者的中位TTP比较差异有统计学意义(x~2=15.77、18.45,P<0.05)。结论:I期NSCLC患者肺癌组织VEGF-C、CK19呈高表达,与术后局部复发密切相关,并可作为患者预后评估的参考指标。
Objective: To analyze the changes in the level of vascular endothelial growth factor C(VEGF-C), cytokeratin 19(CK19) in patients with non-small cell lung cancer(NSCLC) of stage I, and investigate its correlation with the prognosis of postoperative patients. Methods: Immunohistochemistry was used to detect the expression level of VEGF-C, CK19 protein in lung cancer tissue, and its correlation with the clinicopathological characteristics of lung cancer patients was analyzed. All the patients were followed for at least 3 years, Kaplan-Meier was used to analyze the differecnce of postoperative recurrence and time to progress(TTP) between different levels of VEGF-C, CK19 protein expression. Results: There were significant differences in the expression of VEGF-C and CK19 between the lung cancer tissues with different degrees of differentiation and pleural invasion(P<0.05). The expression of VEGF-C and CK19 showed a significant positive correlation(r=0.483, P <0.05). Three years after surgery, the recurrence rates of patients with VEGF-C and CK19 positive expression were significantly higher than those of patients with VEGF-C and CK19 negative expression(x~2=14.16, 17.25, P<0.05). Kaplan-Meier survival analysis showed that the median TTP in positive and negative VEGF-C expression group were 29.2 months(95% CI: 27.5～30.9), 36.2 months(95% CI:35.0～37.5). The median TTP in positive and negative CK19 expression group were 28.4 months(95%CI: 26.6～30.2), 37.8 months(95%CI:36.4～39.1). There were significantly difference on the median TTP between positive and negative VEGF-C and CK19 expression(P<0.05). Conclusions: The expression of VEGF-C and CK19 in the lung cancer tissue of NSCLC patients of stage I were upregulated and closely related to the postoperative local recurrence, it can be used as an reference index for the prognostic evaluation.
Objective: To analyze the changes in the level of vascular endothelial growth factor C(VEGF-C), cytokeratin 19(CK19) in patients with non-small cell lung cancer(NSCLC) of stage I, and investigate its correlation with the prognosis of postoperative patients. Methods: Immunohistochemistry was used to detect the expression level of VEGF-C, CK19 protein in lung cancer tissue, and its correlation with the clinicopathological characteristics of lung cancer patients was analyzed. All the patients were followed for at least 3 years, Kaplan-Meier was used to analyze the differecnce of postoperative recurrence and time to progress(TTP) between different levels of VEGF-C, CK19 protein expression. Results: There were significant differences in the expression of VEGF-C and CK19 between the lung cancer tissues with different degrees of differentiation and pleural invasion(P<0.05). The expression of VEGF-C and CK19 showed a significant positive correlation(r=0.483, P <0.05). Three years after surgery, the recurrence rates of patients with VEGF-C and CK19 positive expression were significantly higher than those of patients with VEGF-C and CK19 negative expression(x~2=14.16, 17.25, P<0.05). Kaplan-Meier survival analysis showed that the median TTP in positive and negative VEGF-C expression group were 29.2 months(95% CI: 27.5～30.9), 36.2 months(95% CI:35.0～37.5). The median TTP in positive and negative CK19 expression group were 28.4 months(95%CI: 26.6～30.2), 37.8 months(95%CI:36.4～39.1). There were significantly difference on the median TTP between positive and negative VEGF-C and CK19 expression(P<0.05). Conclusions: The expression of VEGF-C and CK19 in the lung cancer tissue of NSCLC patients of stage I were upregulated and closely related to the postoperative local recurrence, it can be used as an reference index for the prognostic evaluation.
引文
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[14]Ardizzoni A,Cafferata MA,Tiseo M,et al.Decline in serum carcinoembryonic antigen and cytokeratin 19 fragment during chemotherapy predicts objective response and survival in patients with advanced nonsmall cell lung cancer[J].Cancer,2014,108(12):2842-2849
[15]Sebastian NT,Xu-Welliver M,Williams TM,et al.Stereotactic body radiation therapy(SBRT)for early stage non-small cell lung cancer(NSCLC):contemporary insights and advances[J].J Thorac Dis,2018,10(Suppl 21):S2451-S2464
[16]Goldstraw P,Crow Iey J,Chansky K,et al.The iaslc lung cancers staging project:proposals for the revision of the TNM stage grouping in the forthcoming(seventh)edition of the TNM classification of malignant tumors[J].J Thorac Onco1,2007,2(8):706-714
[17]Lai X,Li Y,Gao M.Biochanin A regulates the growth and migration of NSCLC through suppressing the VEGF/VEGFR2 signaling pathway[J].Oncol Res,2018,23(5):14-19
[18]Stefan H,Birgit W,Karina H,et al.Carcinoembryonic antigen and cytokeratin-19 fragments for assessment of therapy response in non-small cell lung cancer:a systematic review and meta-analysis[J].Br J Cancer,2017,116(8):1037-1045
[19]Holdenrieder S,Nagel D,Stieber P,et al.Estimation of prognosis by circulating biomarkers in patients with non-small cell lung cancer[J].Cancer Biomark,2015,6(12):179-190
[20]Wong SCC,Cheung MT,Luk LLY,et al.Prognostic significance of Cytokeratin 20-positive lymph node vascular endothelial growth factor A mRNA and chromodomain helicase DNA binding protein 4in p N0 colorectal cancer patients[J].Oncotarget,2017,9(6):6737-6751
[21]Videtic GMM,Donington J,Giuliani M,et al.Stereotactic body radiation therapy for early-stage non-small cell lung cancer:Executive Summary of an ASTRO Evidence-Based Guideline[J].Pract Radiat Oncol,2017,7(45):295-301
[22]Nisman B,Biran H,Heching N,et al.Prognostic role of serum cytokeratin 19 fragments in advanced non-small-cell lung cancer:association of marker changes after two chemotherapy cycles with different measures of clinical response and survival[J].Br J Cancer,2013,98(12):77-79
[23]托娅,宋静慧,苏一乐,等.CXCR4、VEGF-C、CK19和EMA在宫颈癌原位灶和淋巴结中的表达及相互关系[J].疾病监测与控制,201314(5):273-275
[24]王耀鹏,王明钊,罗宜人,等.血管内皮生长因子C与细胞角蛋白19检测在Ⅰ期非小细胞肺癌中的临床研究[J].中国胸心血管外科临床杂志,2012,19(4):385-387
[25]Lai Y,Wang X,Zeng T,et al.Serum VEGF levels in the early diagnosis and severity assessment of non-small cell lung cancer[J].JCancer,2018,9(9):1538-1547
[2]韩仁强,郑荣寿,张思维,等.1989年-2008年中国肺癌发病性别、城乡差异及平均年龄趋势分析[J].中国肺癌杂志,2013,16(9):445-451
[3]Jiang W,Chen X,Xi J,et al.Selective mediastinal lymphadenectomy without intraoperative frozen section examinations for clinical stage Inon-small-cell lung cancer:retrospective study of 403 cases[J].World J Surg,2013,37(2):392-397
[4]邵丰,张晓膺.非小细胞肺癌患者术后细胞角蛋白19片段水平与预后的关系[J].江苏医药,2014,40(4):425-427
[5]Lee S,Kang HG,Jin Eun Choi,et al.The Different Effect of VEGFPolymorphisms on the Prognosis of Non-Small Cell Lung Cancer according to Tumor Histology[J].J Korean Med Sci,2016,31(11):1735-1741
[6]Eilertsen M,Pettersen I,Andersen S,et al.In NSCLC,VEGF-Aresponse to hypoxia may differ between squamous cell and adenocarcinoma histology[J].Anticancer Res,2012,32(12):4729-4736
[7]Tu J,Wang S,Zhao J,et al.rs833061 and rs699947 on promoter gene of vascular endothelial growth factor(VEGF)and associated lung cancer susceptibility and survival:a meta-analysis[J].Med Sci Monit,2014,20(12):2520-2526
[8]Samik C,Arghya A,Minakshi M,et al.Capsaicin-Induced Activation of p53-SMAR1 Auto-Regulatory Loop Down-Regulates VEGF in Non-Small Cell Lung Cancer to Restrain Angiogenesis[J].PLo S One,2014,9(6):e99743-99751
[9]Bidard FC,Hajage D,Bachelot T,et al.Assessment of circulating tumor cells and serum markers for progression-free survival prediction in metastatic breast cancer:a prospective observational study[J].Breast Cancer Res,2012,14(1):R29
[10]Pang L,Wang J,Jiang Y,Chen L,et al.Decreased levels of serum cytokeratin 19 fragment CYFRA 21-1 predict objective response to chemotherapy in patients with non-small cell lung cance[J].Exp Ther Med,2013,6(12):355-360
[11]Uhlig S,Hettwer K,Colson B,et al.Carcinoembryonic antigen(CEA)and cytokeratin 19 fragment(CYFRA 21-1)for assessment of therapy response in advanced non-small cell lung cancer:a systematic review and meta-analysis[J].PROSPERO,2015,17(12):974-985
[12]Hung JJ,Jeng WJ,Hsu WH,et al.Predictors of death,local recurrence,and distant metastasis in completely re-sected pathological stage-I non small-cell lung cancer[J].J Thorac Oncol,2012,7(7):1115-1123
[13]Satoh Y,Motosugi U,Saito A,et al.Pretreatment18F-fluorodeoxyglucose Uptake in the Lung Parenchyma Predicts Poor Survival After Stereotactic Body Radiation Therapy in Patients With Stage INon-Small Cell Lung Cancer[J].Technol Cancer Res Treat,2018,17(8):109-123
[14]Ardizzoni A,Cafferata MA,Tiseo M,et al.Decline in serum carcinoembryonic antigen and cytokeratin 19 fragment during chemotherapy predicts objective response and survival in patients with advanced nonsmall cell lung cancer[J].Cancer,2014,108(12):2842-2849
[15]Sebastian NT,Xu-Welliver M,Williams TM,et al.Stereotactic body radiation therapy(SBRT)for early stage non-small cell lung cancer(NSCLC):contemporary insights and advances[J].J Thorac Dis,2018,10(Suppl 21):S2451-S2464
[16]Goldstraw P,Crow Iey J,Chansky K,et al.The iaslc lung cancers staging project:proposals for the revision of the TNM stage grouping in the forthcoming(seventh)edition of the TNM classification of malignant tumors[J].J Thorac Onco1,2007,2(8):706-714
[17]Lai X,Li Y,Gao M.Biochanin A regulates the growth and migration of NSCLC through suppressing the VEGF/VEGFR2 signaling pathway[J].Oncol Res,2018,23(5):14-19
[18]Stefan H,Birgit W,Karina H,et al.Carcinoembryonic antigen and cytokeratin-19 fragments for assessment of therapy response in non-small cell lung cancer:a systematic review and meta-analysis[J].Br J Cancer,2017,116(8):1037-1045
[19]Holdenrieder S,Nagel D,Stieber P,et al.Estimation of prognosis by circulating biomarkers in patients with non-small cell lung cancer[J].Cancer Biomark,2015,6(12):179-190
[20]Wong SCC,Cheung MT,Luk LLY,et al.Prognostic significance of Cytokeratin 20-positive lymph node vascular endothelial growth factor A mRNA and chromodomain helicase DNA binding protein 4in p N0 colorectal cancer patients[J].Oncotarget,2017,9(6):6737-6751
[21]Videtic GMM,Donington J,Giuliani M,et al.Stereotactic body radiation therapy for early-stage non-small cell lung cancer:Executive Summary of an ASTRO Evidence-Based Guideline[J].Pract Radiat Oncol,2017,7(45):295-301
[22]Nisman B,Biran H,Heching N,et al.Prognostic role of serum cytokeratin 19 fragments in advanced non-small-cell lung cancer:association of marker changes after two chemotherapy cycles with different measures of clinical response and survival[J].Br J Cancer,2013,98(12):77-79
[23]托娅,宋静慧,苏一乐,等.CXCR4、VEGF-C、CK19和EMA在宫颈癌原位灶和淋巴结中的表达及相互关系[J].疾病监测与控制,201314(5):273-275
[24]王耀鹏,王明钊,罗宜人,等.血管内皮生长因子C与细胞角蛋白19检测在Ⅰ期非小细胞肺癌中的临床研究[J].中国胸心血管外科临床杂志,2012,19(4):385-387
[25]Lai Y,Wang X,Zeng T,et al.Serum VEGF levels in the early diagnosis and severity assessment of non-small cell lung cancer[J].JCancer,2018,9(9):1538-1547
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