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PLoS One. 2015 Jul 1;10(7):e0132134. doi: 10.1371/journal.pone.0132134. eCollection 2015.

EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas.

Author information

1
Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China; Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, United States of America.
2
Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, United States of America.
3
Department of Oncology, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, China.
4
Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
5
School of Life Sciences, Tsinghua University, Beijing 10084, China.
6
Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
7
Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, United States of America; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing 100142, China.
8
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing 100142, China.
9
Department of Pathology, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.

Abstract

BACKGROUND:

Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer (NSCLC). Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC.

METHODS:

Two independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro.

RESULTS:

EMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration.

CONCLUSIONS:

EMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT). EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy.

PMID:
26132438
PMCID:
PMC4488446
DOI:
10.1371/journal.pone.0132134
[Indexed for MEDLINE]
Free PMC Article

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