WISP-1、WISP-2及WISP-3在非小细胞肺癌中的表达水平
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摘要
目的探讨Wnt诱导分泌型蛋白-1(WISP-1)、WISP-2及WISP-3在非小细胞肺癌(NSCLC)中的表达及临床意义。方法选取2016年1月至2018年1月期间于本院就诊且符合条件的116例NSCLC患者,取其癌组织标本为观察组,取其癌旁正常肺组织为对照组,采用PT-PCR法检测两组WISP-1、WISP-2及WISP-3 mRNA表达情况,采用免疫组化法检测两组WISP-1、WISP-2及WISP-3蛋白阳性表达,并分析其与临床病理参数的相关性。结果观察组WISP-1、WISP-3 mRNA相对表达量分别为(-2.81±0.64)、(-3.54±1.41),显著高于对照组的(-6.45±2.45)、(-6.15±2.72);WISP-2 mRNA相对表达量为(2.51±1.08),显著低于对照组的(4.95±2.36),差异均有统计学意义(P<0.05)。观察组WISP-1、WISP-3阳性表达(69.83%,67.24%)显著高于对照组(31.90%,18.10%),WISP-2阳性表达(46.55%)显著低于对照组(84.48%),差异均有统计学意义(P<0.05)。NSCLC组织中WISP-1阳性表达与病理类型、年龄、是否淋巴结转移相关;WISP-2阳性表达与病理类型、吸烟、TNM分期、组织学分化程度、是否淋巴结转移相关;WISP-3阳性表达与组织学分化程度、TNM分期、年龄相关。结论 WISP-1、WISP-2、WISP-3与NSCLC发生发展密切相关,其中WISP-1、WISP-3可能是致癌基因,其蛋白产物可作为临床干预治疗的重要靶蛋白;WISP-2可能是抑癌基因,可考虑作为临床诊断及预后预测的参考指标。
Objective To investigate the expression and clinical significance of Wnt induced secreted protein-1( WISP-1),WISP-2 and WISP-3 in non-small cell lung cancer(NSCLC). Methods 116 patients with NSCLC who were admitted to our hospital from January 2016 to January 2018 were enrolled. The specimens of the cancer tissues were taken as the observation group, and the normal lung tissues adjacent to the cancer were taken as the control group and WISP-1 mRNA,WISP-2 mRNA and WISP-3 mRNA were detected by PT-PCR. The expressions of WISP-1, WISP-2 and WISP-3 proteins were detected by immunohistochemistry. The correlations between WISP-1, WISP-2 and WISP-3 proteins were analyzed and their correlation with clinicopathological parameters were analyzed. Results The relative expression levels of WISP-1 mRNA and WISP-3 mRNA in the observation group [(-2.81 ±0.64),(-3.54± 1.41) ]were significantly higher than those in the control group [(-6.45±2.45),(-6.15±2.72)]; the relative expression of WISP-2 mRNA( 2.51± 1.08) was significantly lower than that of the control group(4.95 ± 2.36)(P<0.05); the positive expression of WISP-1 and WISP-3 in the observation group(69.83%, 67.24%),was significantly higher than the control group( 31.90%, 18.10%); WISP-2 positive expression(46.55%) was significantly lower than the control group( 84.48%)(P<0.05). The positive expression of WISP-1 in tissues was related to pathological type, age and metastasis; WISP-2 positive expression was associated with pathological type, smoking, TNM stage, histological differentiation, and metastasis; WISP-3 positive expression was related to histological differentiation, TNM staging and age. Conclusions WISP-1, WISP-2 and WISP-3 may be closely related to the development of NSCLC. WISP-1 and WISP-3 may be the NSCLC oncogenes, and may be used as important target proteins for clinical intervention. WISP-2 may be a NSCLC suppressor gene, which can be used as a reference for clinical diagnosis and prognosis prediction.
Objective To investigate the expression and clinical significance of Wnt induced secreted protein-1( WISP-1),WISP-2 and WISP-3 in non-small cell lung cancer(NSCLC). Methods 116 patients with NSCLC who were admitted to our hospital from January 2016 to January 2018 were enrolled. The specimens of the cancer tissues were taken as the observation group, and the normal lung tissues adjacent to the cancer were taken as the control group and WISP-1 mRNA,WISP-2 mRNA and WISP-3 mRNA were detected by PT-PCR. The expressions of WISP-1, WISP-2 and WISP-3 proteins were detected by immunohistochemistry. The correlations between WISP-1, WISP-2 and WISP-3 proteins were analyzed and their correlation with clinicopathological parameters were analyzed. Results The relative expression levels of WISP-1 mRNA and WISP-3 mRNA in the observation group [(-2.81 ±0.64),(-3.54± 1.41) ]were significantly higher than those in the control group [(-6.45±2.45),(-6.15±2.72)]; the relative expression of WISP-2 mRNA( 2.51± 1.08) was significantly lower than that of the control group(4.95 ± 2.36)(P<0.05); the positive expression of WISP-1 and WISP-3 in the observation group(69.83%, 67.24%),was significantly higher than the control group( 31.90%, 18.10%); WISP-2 positive expression(46.55%) was significantly lower than the control group( 84.48%)(P<0.05). The positive expression of WISP-1 in tissues was related to pathological type, age and metastasis; WISP-2 positive expression was associated with pathological type, smoking, TNM stage, histological differentiation, and metastasis; WISP-3 positive expression was related to histological differentiation, TNM staging and age. Conclusions WISP-1, WISP-2 and WISP-3 may be closely related to the development of NSCLC. WISP-1 and WISP-3 may be the NSCLC oncogenes, and may be used as important target proteins for clinical intervention. WISP-2 may be a NSCLC suppressor gene, which can be used as a reference for clinical diagnosis and prognosis prediction.
引文
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[11]陈晟,简易成,周玮,等.Wnt诱导分泌蛋白-1在PHC中的表达及意义[J].同济大学学报:医学版,2016,37(5):29-33.
[12]吴波.WISP1表达与食管鳞状细胞癌患者临床病理表现的相关性研究[D].温州:温州医学院温州医科大学,2013.
[13]梁颖,林勇平,徐韫健,等.非小细胞肺癌EGFR基因突变的异质性[J].热带医学杂志,2015,15(12):1590-1594.
[14]阎红娥,秦越,鲍文华,等.WISP-2及FGFBP1在非小细胞肺癌中的表达[J].黑龙江医药科学,2015,38(2):99-101.
[15]张宇,王海永,管晓龙,等.类风湿关节炎患者关节成纤维样滑膜细胞差异表达的基因分析[J].医学研究生学报,2016,29(6):598-604.
[16]吕建发,邹友成,李学刚,等.非小细胞肺癌组织WISP-3基因表达及其临床意义的探讨[J].中华肿瘤防治杂志,2011,18(13):1021-1023.
[2]Gainor JF,Tan DS,De Pas T,et al.Progression-Free and Overall Survival in ALK-Positive NSCLC Patients Treated with Sequential Crizotinib and Ceritinib[J].Clin Cancer Res,2016,21(12):2745-2752.
[3]Planque N,Perbal B.A structural approach to the role of CCN(CYR61/CTGF/NOV)proteins in tumourigenesis[J].Cancer Cell Int,2003,3(1):15.
[4]张绪超,陆舜,张力,等.中国间变性淋巴瘤激酶(ALK)阳性非小细胞肺癌诊断专家共识(2013版)[J].中华病理学杂志,2013,42(6):402-406.
[5]冯鑫,刘畅,钟殿胜,等.免疫组化染色评分对EGFR突变检测的影响[J].中国肺癌杂志,2015,18(12):740-744.
[6]李歆,李志阳,徐韫健.非小细胞肺癌患者血浆EGFR基因突变的检测[J].热带医学杂志,2017,17(9):1144-1147.
[7]狄春燕,郭含珠.血清Cyr61及CTGF水平与不同分期子宫内膜癌患者肿瘤标志物相关性研究[J].中国妇幼健康研究,2016,27(8):985-986.
[8]Huber MC,Falkenberg N,Hauck SM,et al.Cyr61 and YB-1 are novel interacting partners of u PAR and elevate the malignancy of triple-negative breast cancer[J].Oncotarget,2016,7(28):44062-44075.
[9]杨华宇,马秀梅.肿瘤中CCN蛋白的表达及作用机制[J].临床与实验病理学杂志,2013,29(12):1341-1343.
[10]秦杰,陈瑾,黄守国.WISP-1/NGX6和G3BP/TIP30基因表达对肿瘤细胞增殖转移的影响[J].肿瘤学杂志,2012,18(4):294-297.
[11]陈晟,简易成,周玮,等.Wnt诱导分泌蛋白-1在PHC中的表达及意义[J].同济大学学报:医学版,2016,37(5):29-33.
[12]吴波.WISP1表达与食管鳞状细胞癌患者临床病理表现的相关性研究[D].温州:温州医学院温州医科大学,2013.
[13]梁颖,林勇平,徐韫健,等.非小细胞肺癌EGFR基因突变的异质性[J].热带医学杂志,2015,15(12):1590-1594.
[14]阎红娥,秦越,鲍文华,等.WISP-2及FGFBP1在非小细胞肺癌中的表达[J].黑龙江医药科学,2015,38(2):99-101.
[15]张宇,王海永,管晓龙,等.类风湿关节炎患者关节成纤维样滑膜细胞差异表达的基因分析[J].医学研究生学报,2016,29(6):598-604.
[16]吕建发,邹友成,李学刚,等.非小细胞肺癌组织WISP-3基因表达及其临床意义的探讨[J].中华肿瘤防治杂志,2011,18(13):1021-1023.