甲状腺转录因子1表达与晚期肺腺癌患者一线化疗疗效的关系
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摘要
[目的]探讨甲状腺转录因子1 (TTF-1)表达与晚期肺腺癌患者一线化疗疗效的关系。[方法]选取134例无法手术的Ⅲ～Ⅳ期EGFR及ALK阴性或状态未知的肺腺癌患者。根据免疫组织化学结果分为TTF-1表达阳性组和阴性组,探讨TTF-1表达与患者一线化疗疗效的关系。[结果] 134例患者中,TTF-1阳性表达93例(69.4%),阴性表达41例(30.6%)。TTF-1阳性患者一线化疗的客观缓解率(ORR)及疾病控制率(DCR)均高于TTF-1阴性者(33.3%vs 17.1%;86.0%vs 63.4%,P均<0.05)。124例患者可评价PFS,TTF-1阳性组患者PFS较TTF-1阴性组延长(6.65个月vs 5.00个月,P<0.001)。TTF-1阳性患者1年生存率高于阴性患者(88.2%vs 52.5%,P<0.001)。Cox多因素分析显示,TTF-1表达与PFS相关(HR=0.815,95%CI:0.596～0.982,P=0.004)。[结论] TTF-1表达与不可手术晚期肺腺癌患者一线化疗的PFS相关,可作为晚期患者一线化疗的疗效预测指标。
[Objective] To investigate the relationship between thyroid transcription factor-1(TTF-1) expression and the efficacy of first-line chemotherapy in patients with advanced-stage lung adenocarcinoma. [Methods] One hundred and thirty four patients with unresectable stage Ⅲ～Ⅳ lung adenocarcinoma and EGFR,ALK negative or unknown were enrolled in the study. According to immunohistochemistry results patients were divided into TTF-1 positive and negative groups. The relationship between TTF-1 expression and the efficacy of first-line chemotherapy was analyzed.[Results] In 134 patients,93(69.4%) were positive for TTF-1 and 41(30.6%) were TTF-1 negative. The objective remission rate(ORR) and disease control rate(DCR) in TTF-1-positive patients were significantly higher than those in TTF-1 negative patients(33.3% vs 17.1%,86.0% vs63.4%,both P<0.05). Progress free survival(PFS) was evaluated in 124 patients,the PFS in TTF-1 positive group was longer than that in TTF-1 negative group(6.65 months vs 5.00 months,P <0.001). The 1-year survival of TTF-1 positive patients was higher than that of negative patients(88.2% vs 52.5%,P<0.001). The multivariable Cox proportional hazards model revealed that TTF-1 expression was associated with PFS(HR=0.815,95%CI:0.596～0.982,P=0.004). [Conclusion]The expression of TTF-1 is associated with the PFS of patients with advanced lung adenocarcinoma receiving first-line chemotherapy,which can be used as a prognostic indicator for those patients.
[Objective] To investigate the relationship between thyroid transcription factor-1(TTF-1) expression and the efficacy of first-line chemotherapy in patients with advanced-stage lung adenocarcinoma. [Methods] One hundred and thirty four patients with unresectable stage Ⅲ～Ⅳ lung adenocarcinoma and EGFR,ALK negative or unknown were enrolled in the study. According to immunohistochemistry results patients were divided into TTF-1 positive and negative groups. The relationship between TTF-1 expression and the efficacy of first-line chemotherapy was analyzed.[Results] In 134 patients,93(69.4%) were positive for TTF-1 and 41(30.6%) were TTF-1 negative. The objective remission rate(ORR) and disease control rate(DCR) in TTF-1-positive patients were significantly higher than those in TTF-1 negative patients(33.3% vs 17.1%,86.0% vs63.4%,both P<0.05). Progress free survival(PFS) was evaluated in 124 patients,the PFS in TTF-1 positive group was longer than that in TTF-1 negative group(6.65 months vs 5.00 months,P <0.001). The 1-year survival of TTF-1 positive patients was higher than that of negative patients(88.2% vs 52.5%,P<0.001). The multivariable Cox proportional hazards model revealed that TTF-1 expression was associated with PFS(HR=0.815,95%CI:0.596～0.982,P=0.004). [Conclusion]The expression of TTF-1 is associated with the PFS of patients with advanced lung adenocarcinoma receiving first-line chemotherapy,which can be used as a prognostic indicator for those patients.
引文
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[18]Yang X,Xue LY,Guo L,et al.Clinicopathological and prognostic significance of a panel of tumor biomarkers in lung adenocarcinoma:a tissue microarray study[J].Chinese Journal of Lung Cancer,2014,17(3):243-253.[杨欣,薛丽燕,郭蕾,等.多种肿瘤标志物在肺腺癌中的表达及预后意义的研究[J].中国肺癌杂志,2014,17(3):243-253.]
[19]Sheffield BS,Bosdet IE,Ali RH,et al.Relationship of thyroid transcription factor 1 to EGFR status in non-smallcell lung cancer[J].Curr Oncol,2014,21(6):305-308.
[20]Yao J,Wang JJ,Wang HY,et al.Correlation between TTF-1 expression and EGFR expression and EGFR mutations of 19 and 21 exons in lung adenocarcinoma[J].Chinese Clinical Oncology,2015,20(4):338-342.[姚娟,王建军,王海燕,等.肺腺癌组织中TTF-1与EGFR表达及第19、21号外显子突变的关[J].临床肿瘤学杂志,2015,20(4):338-342.]
[21]Fiala O,Pesek M,Skrickova J,et al.Thyroid transcription factor 1 expression is associated with outcome of patients with non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy[J].Tumour Biol,201,39(2):1-8.
[22]Zhang Y,Wang R,Li Y,et al.Negative thyroid transcription factor 1 expression defines an unfavorable subgroup of lung adenocarcinomas[J].J Thoracic Oncol,2015,10(10):1444-1450.
[2]Kandoth C,McLellan MD,Vandin F,et al.Mutational landscape and significance across 12 major cancer types[J].Nature,2013,502(7471):333-339.
[3]Brambilla E,Travis WD,Colby TV,et al.The new World Health Organization classification of lung tumours[J].Eur Respir J,2001,18:1059-1068.
[4]Shi YK,Sun Y,Yu JM,et al.China experts consensus on the diagnosis and treatment of advanced stage primary lung cancer(2016 Version)[J].Chinese Journal of Lung Cancer,2016,19(1):1-15.[石远凯,孙燕,于金明,等.中国晚期原发性肺癌诊治专家共识(2016年版)[J].中国肺癌杂志,2016,19(1):1-15.]
[5]Wan SZ,Han YP,Huang L,et al.Research of relation and significance between EGFR mutations and TTF-1 in lung adenocarcinoma[J].Journal of Clinical Pulmonary Medicine,2015,20(2):224-227.[万善志,韩一平,黄玲,等.肺腺癌患者EGFR突变与TTF-1的关系及意义研究[J].临床肺科杂志,2015,20(2):224-227.]
[6]Zheng R,Zeng H,Zhang S,et al.National estimates of cancer prevalence in China 2011[J].Cancer Lett,2016,370(1):33-38.
[7]Hong B,van den Heuvel AP,Prabhu VV,et al.Targeting tumor suppressor P53 for cancer therapy:strategies,challenges and opportunities[J].Curr Drug Targets,2014,15(1):80-89.
[8]Gajra A,Lichtman SM.Treatment of advanced lung cancer in the elderly[J].Hosp Pract,2011,39(2):107-115.
[9]Sakashita S,Sakashita M,Sound Tsao M.Genes and pathology of non-small cell lung carcinoma[J].Semin Oncol,2014,41(1):28-39.
[10]Siegelin MD,Borczuk AC.Epidermal growth factor receptor mutations in lung adenocarcinoma[J].Lab Invest,2014,94(2):129-137.
[11]Kim MJ,Shin HC,Shin KC,et al.Best immunohistochemical panel in distinguishing adenocarcinoma from squamous cell carcinoma of lung:tissue microarray assay in resected lung cancer specimens[J].Ann Diagn Pathol,2013,17(1):85-90.
[12]Li B,He X,Luo HT,et al.Value of combined detection of CK7,CK20 and TTF-1 expression evaluating the origin of metastatic adenocarcinoma[J].Chinese Journal of Clinical Oncology,2012,39(10):683-686.[李波,何欣,罗宏涛,等.探讨CK7/CK20和TTF-1在判断转移性腺癌原发病灶中的应用价值[J].中国肿瘤临床,2012,39(10):683-686.]
[13]Xu XY,Liu HW,Jiang H,et al.Combined application of TTF-1,napsin-A and SP-A in differential diagnosis of pulmonary adenocarcinoma from non-pulmonary adenocarcinoma in needle biopsy specimens[J].Chinese Journal of Clinical and Experimental Pathology,2016,23(7):511-515.[徐小艳,刘红伟,姜黄,等.联合应用TTF-1,Napsin-A和SP-A在穿刺活检标本中肺源性腺癌和非肺源性腺癌的诊断意义[J].临床诊断病理学杂志,2016,23(7):511-515.]
[14]Ao MH,Zhang H,Sakowski L,et al.The utility of a novel triple marker(combination of TTF1,napsin A,and p40)in the subclassification of non-small cell lung cancer[J].Hum Pathol,2014,45(5):926-934.
[15]Gao FP,Wei J,Ma P,et al.Differential diagnostic significance of p63 and TTF-1 between adenocarcinoma of lung and squamous cell carcinoma[J].Journal of Clinical Pulmonary Medicine,2014.19(1):112-113.[高福平,魏谨,马平,等.TTF-1和p63在肺腺癌与鳞癌的鉴别中的意义[J].临床肺科杂志,2014,19(1):112-113.]
[16]Sun X,Yu B,Zhang RS,et al.Correlation between TTF-1protein expression and EGFR mutation in lung adenocarcinoma[J].Chinese Journal of Clinical and Experimental Pathology,2015,31(2):192-194.[孙绪,余波,章如松,等.肺腺癌组织中TTF-1蛋白表达与EGFR突变的相关性[J],临床与实验病理学杂志,2015,31(2):192-194.]
[17]Rekhtman N,Ang DC,Sima CS,et al.Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens[J].Mod Pathol,2011,24(10):1348-1359.
[18]Yang X,Xue LY,Guo L,et al.Clinicopathological and prognostic significance of a panel of tumor biomarkers in lung adenocarcinoma:a tissue microarray study[J].Chinese Journal of Lung Cancer,2014,17(3):243-253.[杨欣,薛丽燕,郭蕾,等.多种肿瘤标志物在肺腺癌中的表达及预后意义的研究[J].中国肺癌杂志,2014,17(3):243-253.]
[19]Sheffield BS,Bosdet IE,Ali RH,et al.Relationship of thyroid transcription factor 1 to EGFR status in non-smallcell lung cancer[J].Curr Oncol,2014,21(6):305-308.
[20]Yao J,Wang JJ,Wang HY,et al.Correlation between TTF-1 expression and EGFR expression and EGFR mutations of 19 and 21 exons in lung adenocarcinoma[J].Chinese Clinical Oncology,2015,20(4):338-342.[姚娟,王建军,王海燕,等.肺腺癌组织中TTF-1与EGFR表达及第19、21号外显子突变的关[J].临床肿瘤学杂志,2015,20(4):338-342.]
[21]Fiala O,Pesek M,Skrickova J,et al.Thyroid transcription factor 1 expression is associated with outcome of patients with non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy[J].Tumour Biol,201,39(2):1-8.
[22]Zhang Y,Wang R,Li Y,et al.Negative thyroid transcription factor 1 expression defines an unfavorable subgroup of lung adenocarcinomas[J].J Thoracic Oncol,2015,10(10):1444-1450.