Prognostic value of high FoxC2 expression in resectable non-small cell lung cancer, alone or in combination with E-cadherin expression

被引:22
作者
Jiang, Wei [1 ]
Fan, Hong [1 ]
Qian, Cheng [1 ]
Ding, Jianyong [1 ]
Wang, Qun [1 ]
Pang, Xuguang [1 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Dept Thorac Surg, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
Lung cancer; FoxC2; E-cadherin; Prognosis; Immunohistochemistry; EPITHELIAL-MESENCHYMAL TRANSITION; CLINICAL-SIGNIFICANCE; TRANSCRIPTION FACTOR; TUMOR PROGRESSION; GENE-EXPRESSION; METASTASIS; ANGIOGENESIS; P120-CATENIN; MECHANISMS; CARCINOMA;
D O I
10.1186/s12885-016-2056-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: FoxC2 is an epithelial-mesenchymal transition (EMT) regulator which induces metastasis. The purpose of this study is to assess the prognostic value of FoxC2 expression in non-small cell lung cancer (NSCLC), alone or in combination with E-cadherin expression. Methods: A retrospective study was conducted using immunohistochemistry to investigate FoxC2 and E-cadherin expression in a cohort of 309 patients with surgically resected NSCLCs. The prognostic value of FoxC2 and E-cadherin on overall survival (OS) and recurrence-free survival (RFS) was determined by Kaplan-Meier analysis and Cox proportional hazard models. Results: High FoxC2 expression was detected in 26.5 % of tumors, and significantly correlated with tobacco use (p = 0.047), adenocarcinoma (p = 0.008) and nodal involvement (p < 0.001). Univariate analysis revealed its association with OS (p = 0.036) and RFS (p = 0.011). By multivariate analysis, high FoxC2 expression lost its significance as an independent predictor of recurrence (p = 0.077), while TNM stage, nodal status and the presence of high FoxC2 and impaired E-cadherin expression retained independent prognostic significance in relation to both OS and RFS. Subset analyses indicated that high FoxC2 expression was significantly associated with disease outcome in node-positive, but not in node-negative patients. Conclusion: Evaluation of FoxC2 expression, alone or in combination with E-cadherin expression, may help to stratify NSCLC patients for risk of disease progression, pointing to this EMT regulator as a potential prognostic marker.
引用
收藏
页数:9
相关论文
共 23 条
[1]   Role of the epithelial-mesenchymal transition regulator Slug in primary human cancers [J].
Alves, Catarina Castro ;
Carneiro, Fatima ;
Hoefler, Heinz ;
Becker, Karl-Friedrich .
FRONTIERS IN BIOSCIENCE-LANDMARK, 2009, 14 :3041-3050
[2]   Epithelial mesenchymal interactions in cancer and development [J].
Arias, AM .
CELL, 2001, 105 (04) :425-431
[3]   Cell adhesion and signalling by cadherins and Ig-CAMs in cancer [J].
Cavallaro, U ;
Christofori, G .
NATURE REVIEWS CANCER, 2004, 4 (02) :118-132
[4]   Cancer metastasis:: Building a framework [J].
Gupta, Gaorav P. ;
Massague, Joan .
CELL, 2006, 127 (04) :679-695
[5]   FOXC2 Expression Links Epithelial-Mesenchymal Transition and Stem Cell Properties in Breast Cancer [J].
Hollier, Brett G. ;
Tinnirello, Agata A. ;
Werden, Steven J. ;
Evans, Kurt W. ;
Taube, Joseph H. ;
Sarkar, Tapasree Roy ;
Sphyris, Nathalie ;
Shariati, Maryam ;
Kumar, Sreedevi V. ;
Battula, Venkata L. ;
Herschkowitz, Jason I. ;
Guerra, Rudy ;
Chang, Jeffrey T. ;
Miura, Naoyuki ;
Rosen, Jeffrey M. ;
Mani, Sendurai A. .
CANCER RESEARCH, 2013, 73 (06) :1981-1992
[6]   Cancer statistics, 2008 [J].
Jemal, Ahmedin ;
Siegel, Rebecca ;
Ward, Elizabeth ;
Hao, Yongping ;
Xu, Jiaquan ;
Murray, Taylor ;
Thun, Michael J. .
CA-A CANCER JOURNAL FOR CLINICIANS, 2008, 58 (02) :71-96
[7]   Prognostic Role of Twist, Slug, and Foxc2 Expression in Stage I Non-Small-Cell Lung Cancer After Curative Resection [J].
Jiang, Wei ;
Pang, Xu-Guang ;
Wang, Qun ;
Shen, Ya-Xing ;
Chen, Xiao-Ke ;
Xi, Jun-Jie .
CLINICAL LUNG CANCER, 2012, 13 (04) :280-287
[8]   Foxc2 Transcription Factor: A Newly Described Regulator of Angiogenesis [J].
Kume, Tsutomu .
TRENDS IN CARDIOVASCULAR MEDICINE, 2008, 18 (06) :224-228
[9]   Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition [J].
Lee, Terence K. ;
Poon, Ronnie T. P. ;
Yuen, Anthony P. ;
Ling, Ming Tat ;
Kwok, Wei Kei ;
Wang, Xiang Hong ;
Wong, Yong Chuan ;
Guan, Xin Yuan ;
Man, Kwan ;
Chau, King Lok ;
Fan, Sheung Tat .
CLINICAL CANCER RESEARCH, 2006, 12 (18) :5369-5376
[10]   Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers [J].
Mani, Sendurai A. ;
Yang, Jing ;
Brooks, Mary ;
Schwaninger, Gunda ;
Zhou, Alicia ;
Miura, Naoyuki ;
Kutok, Jeffery L. ;
Hartwell, Kimberly ;
Richardson, Andrea L. ;
Weinberg, Robert A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (24) :10069-10074