GATA6和TPM1在非小细胞肺癌中的表达及临床意义
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摘要
目的检测转录因子GATA6和原肌球蛋白1(TPM1)在非小细胞肺癌(NSCLC)中的表达情况,探讨两者在NSCLC中的临床意义。方法选取在本院治疗的NSCLC患者60例,采用PCR技术检测NSCLC患者癌组织及对应癌旁组织中GATA6和TPM1基因表达情况,免疫组织化学法检测GATA6和TPM1蛋白表达,并分析GATA6和TPM1表达水平与各临床病理参数的关系。Cox回归模型分析GATA6和TPM1表达与NSCLC患者预后影响。结果 60例NSCLC患者癌组织中GATA6基因表达水平及阳性表达率均明显高于癌旁组织,而TPM1基因表达水平及阳性表达率均明显低于癌旁组织(P <0.05)。GATA6和TPM1蛋白表达情况与患者年龄、分化等级、肿瘤分期、TNM分期均无关系(P> 0.05);GATA6蛋白表达情况与淋巴结是否出现转移密切相关(P <0.05),TPM1的蛋白表达情况与患者病理分类密切相关(P <0.05)。GATA6和TPM1以及是否出现淋巴结转移是影响NSCLC患者预后的主要危险因素(P <0.05)。结论 GATA6和TPM1在NSCLC组织中呈异常表达,且是影响NSCLC预后的危险因素,两者均在NSCLC发生发展及预后评估中具有重要的意义,可为靶向治疗提供参考依据。
Objective To investigate the expressions of transcription factor GATA6 and tropomyosin 1(TPM1) in non-small cell lung cancer(NSCLC) and their clinical significances. Methods 60 patients with NSCLC in our hospital were selected, PCR were used to detect the expressions of GATA6 and TPM1 in cancerous tissues and corresponding adjacent tissues of NSCLC patients, the expressions of GATA6 and TPM1 proteins were detected by immunohistochemistry, the relationships between the expression levels of GATA6 and TPM1 with clinicopathological parameters were also analyzed. Cox regression model was used to analyze the prognostic significances of GATA6 and TPM1 expressions in patients with NSCLC. Results The expression level and positive rate of GATA6 gene in cancer tissues of 60 NSCLC patients were significantly higher than those in para cancerous tissues, while the expression level and positive rate of TPM1 gene were significantly lower than those in adjacent tissues(P < 0.05). The expressions of GATA6 and TPM1 were not correlated with age, differentiation grade, tumor stage and TNM stage(P > 0.05); the expression of GATA6 protein was closely related to lymph node metastasis(P < 0.05), and the expression of TPM1 protein was closely related to pathological classification(P < 0.05). GATA6, TPM1 and lymph node metastasis were the main risk factors for the prognosis of NSCLC patients(P < 0.05). Conclusion GATA6 and TPM1 are abnormally expressed in NSCLC tissues, and are risk factors for prognosis of NSCLC. Both of them have important significances in the occurrence, development and prognosis evaluation of NSCLC, which can provide reference for targeted therapy.
Objective To investigate the expressions of transcription factor GATA6 and tropomyosin 1(TPM1) in non-small cell lung cancer(NSCLC) and their clinical significances. Methods 60 patients with NSCLC in our hospital were selected, PCR were used to detect the expressions of GATA6 and TPM1 in cancerous tissues and corresponding adjacent tissues of NSCLC patients, the expressions of GATA6 and TPM1 proteins were detected by immunohistochemistry, the relationships between the expression levels of GATA6 and TPM1 with clinicopathological parameters were also analyzed. Cox regression model was used to analyze the prognostic significances of GATA6 and TPM1 expressions in patients with NSCLC. Results The expression level and positive rate of GATA6 gene in cancer tissues of 60 NSCLC patients were significantly higher than those in para cancerous tissues, while the expression level and positive rate of TPM1 gene were significantly lower than those in adjacent tissues(P < 0.05). The expressions of GATA6 and TPM1 were not correlated with age, differentiation grade, tumor stage and TNM stage(P > 0.05); the expression of GATA6 protein was closely related to lymph node metastasis(P < 0.05), and the expression of TPM1 protein was closely related to pathological classification(P < 0.05). GATA6, TPM1 and lymph node metastasis were the main risk factors for the prognosis of NSCLC patients(P < 0.05). Conclusion GATA6 and TPM1 are abnormally expressed in NSCLC tissues, and are risk factors for prognosis of NSCLC. Both of them have important significances in the occurrence, development and prognosis evaluation of NSCLC, which can provide reference for targeted therapy.
引文
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[7]Feng J,Ni SS,Zhou XY.Expression and clinical value of cathepsin Bin non-small cell lung cancer.Jiangsu Med J,2009,35(9):1028-1030.(in Chinese)冯健,倪松石,周晓宇.组织蛋白酶B在非小细胞肺癌中的表达及临床意义.江苏医药,2009,35(9):1028-1030.
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[11]Franco A,Zhang L,Matkovich SJ,et al.G-protein receptor kinases 2,5 and 6 redundantly modulate Smoothened-GATA transcriptional crosstalk in fetal mouse hearts.J Mol Cell Cardiol,2018,121:60-68.
[12]Belaguli NS,Aftab M,Rigi M,et al.GATA6 promotes colon cancer cell invasion by regulating urokinase plasminogen activator gene expression.Neoplasia,2010,12(11):856-864.
[13]Tang Y,Wei Y,He W,et al.GATA transcription factors in vertebrates:evolutionary,structural and functional interplay.Mol Genet Genomics,2014,289(2):203-214.
[14]Kwei KA,Bashyam MD,Kao J,et al.Genomic profiling identifies GATA6 as a candidate oncogene amplified in pancreatobiliary cancer.PLoS Genet,2008,4(5):e1000081.
[15]Williams MR,Tardiff JC,Schwartz SD.Mechanism of cardiac tropomyosin transitions on filamentous actin as revealed by all-atom steered molecular dynamics simulations.J Phys Chem Lett,2018,9(12):3301-3306.
[16]Reumiller CM,Schmidt GJ,Dhrami I,et al.Gender-related increase of tropomyosin-1 abundance in platelets of Alzheimer's disease and mild cognitive impairment patients.J Proteomics,2018,178:73-81.
[17]Wang L,Lin JL.TPM1 expression and its clinical significance in nasopharyngeal carcinoma.Chin J Mod Drug Appl,2014,8(19):17-19.(in Chinese)王亮,林建立.TPM1在鼻咽癌中的表达及其临床意义.中国现代药物应用,2014,8(19):17-19.
[18]Nijak A,Alaerts M,Kuiperi C,et al.Left ventricular non-compaction with Ebstein anomaly attributed to a TPM1 mutation.Eur J Med Genet,2018,61(1):8-10.
[19]Veeranan-Karmegam R,Boggupalli DP,Liu G,et al.A new isoform of Drosophila non-muscle Tropomyosin 1 interacts with Kinesin-1 and functions in oskar mRNA localization.J Cell Sci,2016,129(22):4252-4264.
[20]Li MN,Zhang WM,Cao HL,et al.Expression and significance of tropomyosin 1 in non-small cell lung cancer.Jiangsu Med J,2010,36(9):2133-2136,cover 2.(in Chinese)李明娜,张炜明,曹海龙,等.原肌球蛋白1在非小细胞肺癌中的表达及意义.江苏医药,2010,36(9):2133-2136,封2.
[2]Molkentin JD.The zinc finger-containing transcription factors GATA-4,-5,and-6.Ubiquitously expressed regu-lators of tissuespecific gene expression.J Biol Chem,2000,275(50):38949-38952.
[3]Bossard P,Zaret KS.GATA transcription factors as potentiators of gut endoderm differentiation.Development,1998,125(24):4909-4917.
[4]Zhao W,Zhao YB,Zhang SB,et al.Research progress of transcriptin regulator GATA6 in tumor.J Mod Oncol,2018,26(6):955-957.(in Chinese)赵蔚,赵艳滨,张诗博,等.转录调节因子GATA6在肿瘤中的研究进展.现代肿瘤医学,2018,26(6):955-957.
[5]Decker K,Goldman DC,Grasch CL,et al.Gata6 is an important regulator of mouse pancreas development.Dev Biol,2006,298(2):415-429.
[6]Tang C,Wang J,Wei Q,et al.Tropomyosin-1 promotes cancer cell apoptosis via the p53-mediated mitochondrial pathway in renal cell carcinoma.Oncol Lett,2018,15(5):7060-7068.
[7]Feng J,Ni SS,Zhou XY.Expression and clinical value of cathepsin Bin non-small cell lung cancer.Jiangsu Med J,2009,35(9):1028-1030.(in Chinese)冯健,倪松石,周晓宇.组织蛋白酶B在非小细胞肺癌中的表达及临床意义.江苏医药,2009,35(9):1028-1030.
[8]Jemal A,Siegel R,Ward E,et al.Cancer statistics,2009.CA Cancer J Clin,2009,59(4):225-249.
[9]Ferlay J,Shin HR,Bray F,et al.Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008.Int J Cancer,2010,127(12):2893-2917.
[10]Song SY,DAS AK,Minna JD.Comparison between concurrent and sequential chemoradiation for non-small cell lung cancer in vitro.Oncol Lett,2014,7(2):307-310.
[11]Franco A,Zhang L,Matkovich SJ,et al.G-protein receptor kinases 2,5 and 6 redundantly modulate Smoothened-GATA transcriptional crosstalk in fetal mouse hearts.J Mol Cell Cardiol,2018,121:60-68.
[12]Belaguli NS,Aftab M,Rigi M,et al.GATA6 promotes colon cancer cell invasion by regulating urokinase plasminogen activator gene expression.Neoplasia,2010,12(11):856-864.
[13]Tang Y,Wei Y,He W,et al.GATA transcription factors in vertebrates:evolutionary,structural and functional interplay.Mol Genet Genomics,2014,289(2):203-214.
[14]Kwei KA,Bashyam MD,Kao J,et al.Genomic profiling identifies GATA6 as a candidate oncogene amplified in pancreatobiliary cancer.PLoS Genet,2008,4(5):e1000081.
[15]Williams MR,Tardiff JC,Schwartz SD.Mechanism of cardiac tropomyosin transitions on filamentous actin as revealed by all-atom steered molecular dynamics simulations.J Phys Chem Lett,2018,9(12):3301-3306.
[16]Reumiller CM,Schmidt GJ,Dhrami I,et al.Gender-related increase of tropomyosin-1 abundance in platelets of Alzheimer's disease and mild cognitive impairment patients.J Proteomics,2018,178:73-81.
[17]Wang L,Lin JL.TPM1 expression and its clinical significance in nasopharyngeal carcinoma.Chin J Mod Drug Appl,2014,8(19):17-19.(in Chinese)王亮,林建立.TPM1在鼻咽癌中的表达及其临床意义.中国现代药物应用,2014,8(19):17-19.
[18]Nijak A,Alaerts M,Kuiperi C,et al.Left ventricular non-compaction with Ebstein anomaly attributed to a TPM1 mutation.Eur J Med Genet,2018,61(1):8-10.
[19]Veeranan-Karmegam R,Boggupalli DP,Liu G,et al.A new isoform of Drosophila non-muscle Tropomyosin 1 interacts with Kinesin-1 and functions in oskar mRNA localization.J Cell Sci,2016,129(22):4252-4264.
[20]Li MN,Zhang WM,Cao HL,et al.Expression and significance of tropomyosin 1 in non-small cell lung cancer.Jiangsu Med J,2010,36(9):2133-2136,cover 2.(in Chinese)李明娜,张炜明,曹海龙,等.原肌球蛋白1在非小细胞肺癌中的表达及意义.江苏医药,2010,36(9):2133-2136,封2.