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Article ; Online: Treatment Decision Drivers in Stage III Non-Small-Cell Lung Cancer: Outcomes of a Web-Based Survey of Oncologists in the United States.

Cotarla, Ion / Boron, Marnie L / Cullen, Shawna L / Spinner, Daryl S / Faulkner, Eric C / Carroll, Marissa C / Shah, Surbhi / Yagui-Beltran, Adam

JCO oncology practice

2020 Volume 16, Issue 10, Page(s) e1232–e1242

Abstract: Purpose: We conducted a cross-sectional survey of practicing medical oncologists in the United States to obtain insight into physician and patient treatment decision making in stage III non-small-cell lung cancer (NSCLC).: Methods: A convenience ... ...

Abstract	Purpose: We conducted a cross-sectional survey of practicing medical oncologists in the United States to obtain insight into physician and patient treatment decision making in stage III non-small-cell lung cancer (NSCLC). Methods: A convenience sample of 150 oncologists completed a 38-question Web-based survey in January 2019. Results: Surveyed oncologists (82% community based) had an average of 15 years of clinical experience and had treated an average of 20 patients newly diagnosed with stage III NSCLC in the previous 6 months. Oncologists reported presenting 55% of their patients with stage III NSCLC to tumor boards. For patients with new unresectable stage III NSCLC seen in the previous 6 months, concurrent chemoradiation therapy (cCRT) was reported as the initial treatment in an average of 48% of patients. The most frequent reason for delays in starting the initial chosen treatment was insurance preauthorization processes (reported by 65% of oncologists). A total of 55% of all patients with unresectable stage III NSCLC who received cCRT went on to receive consolidation immunotherapy; for patients who received consolidation chemotherapy after cCRT, the rate of immunotherapy was lower (42%). Biomarker test results were given as the reason for oncologists not recommending immunotherapy after cCRT in approximately a quarter of cases. The 112 oncologists with eligible patients who declined immunotherapy reported previous treatment fatigue as the reason in 34% of patients and insurance challenges in 19% of patients. Conclusion: Oncologists reported notable deviations from treatment guidelines for stage III NSCLC. Our findings highlight important opportunities to improve decision making and the coordination of care in stage III NSCLC.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/therapy ; Chemoradiotherapy ; Clinical Decision-Making ; Cross-Sectional Studies ; Humans ; Immunotherapy ; Internet ; Lung Neoplasms/therapy ; Neoplasm Staging ; Oncologists ; Practice Patterns, Physicians' ; Surveys and Questionnaires ; United States
Language	English
Publishing date	2020-06-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3028198-2
ISSN	2688-1535 ; 2688-1527
ISSN (online)	2688-1535
ISSN	2688-1527
DOI	10.1200/JOP.19.00781
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Zs.A 7198: Show issues

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Article ; Online: Cancer stem cells in lung tumorigenesis.

Kratz, Johannes R / Yagui-Beltrán, Adam / Jablons, David M

The Annals of thoracic surgery

2010 Volume 89, Issue 6, Page(s) S2090–5

Abstract: Although stem cells were discovered more than 50 years ago, we have only recently begun to understand their potential importance in cancer biology. Recent advances in our ability to describe, isolate, and study lung stem cell populations has led to a ... ...

Abstract	Although stem cells were discovered more than 50 years ago, we have only recently begun to understand their potential importance in cancer biology. Recent advances in our ability to describe, isolate, and study lung stem cell populations has led to a growing recognition of the central importance cells with stem cell-like properties may have in lung tumorigenesis. This article reviews the major studies supporting the existence and importance of cancer stem cells in lung tumorigenesis. Continued research in the field of lung cancer stem cell biology is vital, as ongoing efforts promise to yield new prognostic and therapeutic targets.
MeSH term(s)	Humans ; Lung Neoplasms/etiology ; Neoplastic Stem Cells
Language	English
Publishing date	2010-05-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2010.03.038
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Zs.A 252: Show issues

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Article: Respiratory Homeostasis and Exploitation of the Immune System for Lung Cancer Vaccines.

Yagui-Beltrán, Adam / Coussens, Lisa M / Jablons, David M

US oncology

2010 Volume 58, Issue 1, Page(s) 40–48

Abstract: Lung cancer is the leading cause of all cancer deaths in the US. The international scientific and clinical community has made significant advances toward understanding specific molecular mechanisms underlying lung carcinogenesis; however, despite these ... ...

Abstract	Lung cancer is the leading cause of all cancer deaths in the US. The international scientific and clinical community has made significant advances toward understanding specific molecular mechanisms underlying lung carcinogenesis; however, despite these insights and advances in surgery and chemoradiotherapy, the prognosis for non-small-cell lung cancer (NSCLC) remains poor. Nonetheless, significant effort is being focused on advancing translational research evaluating the efficacy of novel targeted therapeutic strategies for lung cancer. Illustrative examples of this include antagonists of the epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, and a diverse assortment of anti-angiogenic compounds targeting growth factors and/or their receptors that regulate tumor-associated angiogenic programs. In addition, with the increased awareness of the significant role chronically activated leukocytes play as potentiators of solid-tumor development, the role of innate and adaptive immune cells as regulators of lung carcinogenesis is being examined. While some of these studies are examining how novel therapeutic strategies may enhance the efficacy of lung cancer vaccines, others are evaluating the intrinsic characteristics of the immune response to lung cancer in order to identify rate-limiting molecular and/or cellular programs to target with novel anticancer therapeutics. In this article, we explore important aspects of the immune system and its role in regulating normal respiratory homeostasis compared with the immune response accompanying development of lung cancer. These hallmarks are then discussed in the context of recent efforts to develop lung cancer vaccines, where we have highlighted important concepts that must be taken into consideration for future development of novel therapeutic strategies and clinical trials assessing their efficacy.
Language	English
Publishing date	2010-02-25
Publishing country	England
Document type	Journal Article
ISSN	1758-4027
ISSN	1758-4027
DOI	10.17925/ohr.2009.05.1.40
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Article ; Online: A translational approach to lung cancer research: From EGFRs to Wnt and cancer stem cells.

Yagui-Beltrán, Adam / Jablons, David M

Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia

2009 Volume 15, Issue 4, Page(s) 213–220

Abstract: Lung cancer remains the main cause of all cancer deaths in the United States. The prognosis for non-small cell lung cancer, despite advances in current therapies, is disappointing. Fortunately, we are steadily gaining significant insights into the ... ...

Abstract	Lung cancer remains the main cause of all cancer deaths in the United States. The prognosis for non-small cell lung cancer, despite advances in current therapies, is disappointing. Fortunately, we are steadily gaining significant insights into the heterogeneous molecular pathogenesis of lung cancer, which seems to occur in a stepwise manner, mainly secondary to tobacco smoking. With the emerging power of gene expression signatures for individual lung tumors and with the advancing field of stem cell biology and the paradigm of cancer stem cells, we are most certainly paving the way to developing novel tools for the early detection, chemoprevention, and treatment of these vastly morbid pathologies with enormous global burden. We will explore some of these issues and highlight how we are starting to translate them into clinically relevant tools for lung cancer patients.
MeSH term(s)	Angiogenesis Inhibitors/therapeutic use ; Animals ; Biomedical Research/trends ; Carcinoma, Non-Small-Cell Lung/blood supply ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/metabolism ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/therapy ; Epigenesis, Genetic ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/genetics ; ErbB Receptors/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunotherapy/methods ; Lung Neoplasms/blood supply ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Lung Neoplasms/therapy ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/prevention & control ; Protein Kinase Inhibitors/therapeutic use ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Wnt Proteins/genetics ; Wnt Proteins/metabolism
Chemical Substances	Angiogenesis Inhibitors ; Protein Kinase Inhibitors ; Wnt Proteins ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2009-09-17
Publishing country	Japan
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2019756-1
ISSN	2186-1005 ; 1341-1098
ISSN (online)	2186-1005
ISSN	1341-1098
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Zs.A 5253: Show issues

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Article: The role of cancer stem cells in neoplasia of the lung: past, present and future.

Yagui-Beltrán, Adam / He, Biao / Jablons, David M

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico

2008 Volume 10, Issue 11, Page(s) 719–725

Abstract: Through the identification and subsequent targeting of an exquisitely unique and phenotypically defined cancer stem-cell population exhibiting discrete therapeutic vulnerabilities (a potential source of tumor recurrence) better survival rates for these ... ...

Abstract	Through the identification and subsequent targeting of an exquisitely unique and phenotypically defined cancer stem-cell population exhibiting discrete therapeutic vulnerabilities (a potential source of tumor recurrence) better survival rates for these patients may be achieved. It is this impetus that is making the field of pulmonary stem cell biology a growing field in biomedicine. These efforts are leading to the steady identification of multi-potent, self-renewing and proliferative progenitor cell populations throughout the bronchopulmonary tree. These cells give rise to both transiently amplifying (TA) and terminally differentiated (TD) cells, which (like in many other organs) are crucial for tissue homeostasis. In leukemia, it has been shown that partially committed cells, which are normally responsible for tissue maintenance after trauma, may undergo transformation via mutations resulting in the selective expression of genes that accentuate and perpetuate these cells' self-renewal capabilities. It is therefore perhaps legitimate to consider stem cells as protumorigenic. It is when these cells undergo genetic mutations which make them acquire the ability to metastasize, that cancer occurs, rendering the concept of "cancer stem cells" a rather attractive one indeed.
MeSH term(s)	Animals ; Antigens, Differentiation/analysis ; Biomarkers, Tumor/analysis ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/pathology ; Forecasting ; Gene Expression Profiling ; Hedgehog Proteins/genetics ; Hedgehog Proteins/physiology ; Humans ; Lung Neoplasms/etiology ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Lung Neoplasms/therapy ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mutation ; Neoplasm Proteins/genetics ; Neoplasm Proteins/physiology ; Neoplasm Transplantation ; Neoplastic Stem Cells/pathology ; Receptors, Notch/genetics ; Receptors, Notch/physiology ; Signal Transduction ; Stem Cells/pathology ; Wnt Proteins/genetics ; Wnt Proteins/physiology
Chemical Substances	Antigens, Differentiation ; Biomarkers, Tumor ; Hedgehog Proteins ; Neoplasm Proteins ; Receptors, Notch ; Wnt Proteins
Language	English
Publishing date	2008-10-22
Publishing country	Italy
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2397359-6
ISSN	1699-3055 ; 1699-048X
ISSN (online)	1699-3055
ISSN	1699-048X
DOI	10.1007/s12094-008-0278-6
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Zs.A 6644: Show issues

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Article ; Online: Optimal surgical management of Stage I non-small-cell lung cancer in an increasingly aging population: challenges and recent progress.

Yagui-Beltrán, Adam / Jablons, David M

Expert review of respiratory medicine

2007 Volume 1, Issue 3, Page(s) 343–353

Abstract: Lung cancer remains the main cause of cancer deaths in the USA. The dismal prognosis for non-small-cell lung cancer (NSCLC) despite current advances in chemotherapy is disappointing. In an increasingly aging population, computed tomography screening ... ...

Abstract	Lung cancer remains the main cause of cancer deaths in the USA. The dismal prognosis for non-small-cell lung cancer (NSCLC) despite current advances in chemotherapy is disappointing. In an increasingly aging population, computed tomography screening allows the detection of very early Stage I NSCLC lesions. Although many retrospective trials have indicated better prognosis for those undergoing lobectomy versus sublobar resection (anatomical segmentectomy or wedge resection), the issue remains equivocal. This is particularly true for patients with significant comorbid cardiorespiratory disease compromising postoperative recovery. This review will describe landmark retrospective studies related to the topic, in an attempt to highlight the difficulties associated with surgical decision making. Key factors in the characteristics of the lesions will be examined equally with the ultimate objective of allowing the decision of lobectomy versus sublobar resection to be centered around the need of the individual patient per se. This review article will also provide an insight into ongoing randomized, prospective clinical trials on the subject, investigating into some of the emerging technologies from the laboratory and the clinic that will hopefully enable the provision of a solidly acceptable treatment plan for the Stage I NSCLC patient, with maximum survival rates and low disease recurrence.
Language	English
Publishing date	2007-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2479146-5
ISSN	1747-6356 ; 1747-6348
ISSN (online)	1747-6356
ISSN	1747-6348
DOI	10.1586/17476348.1.3.343
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Zs.A 6963: Show issues

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Article ; Online: Tumor-infiltrating regulatory T cells inhibit endogenous cytotoxic T cell responses to lung adenocarcinoma.

Ganesan, Anusha-Preethi / Johansson, Magnus / Ruffell, Brian / Yagui-Beltrán, Adam / Beltran, Adam / Lau, Jonathan / Jablons, David M / Coussens, Lisa M

Journal of immunology (Baltimore, Md. : 1950)

2013 Volume 191, Issue 4, Page(s) 2009–2017

Abstract: Immune cells comprise a substantial proportion of the tumor mass in human nonsmall cell lung cancers (NSCLC), but the precise composition and significance of this infiltration are unclear. In this study, we examined immune complexity of human NSCLC as ... ...

Abstract	Immune cells comprise a substantial proportion of the tumor mass in human nonsmall cell lung cancers (NSCLC), but the precise composition and significance of this infiltration are unclear. In this study, we examined immune complexity of human NSCLC as well as NSCLC developing in CC10-TAg transgenic mice, and revealed that CD4(+) T lymphocytes represent the dominant population of CD45(+) immune cells, and, relative to normal lung tissue, CD4(+)Foxp3(+) regulatory T cells (Tregs) were significantly increased as a proportion of total CD4(+) cells. To assess the functional significance of increased Tregs, we evaluated CD8(+) T cell-deficient/CC10-TAg mice and revealed that CD8(+) T cells significantly controlled tumor growth with antitumor activity that was partially repressed by Tregs. However, whereas treatment with anti-CD25-depleting mAb as monotherapy preferentially depleted Tregs and improved CD8(+) T cell-mediated control of tumor progression during early tumor development, similar monotherapy was ineffective at later stages. Because mice bearing early NSCLC treated with anti-CD25 mAb exhibited increased tumor cell death associated with infiltration by CD8(+) T cells expressing elevated levels of granzyme A, granzyme B, perforin, and IFN-γ, we therefore evaluated carboplatin combination therapy resulting in a significantly extended survival beyond that observed with chemotherapy alone, indicating that Treg depletion in combination with cytotoxic therapy may be beneficial as a treatment strategy for advanced NSCLC.
MeSH term(s)	Adenocarcinoma/immunology ; Animals ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents, Alkylating/administration & dosage ; Antineoplastic Agents, Alkylating/therapeutic use ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/pathology ; Carboplatin/administration & dosage ; Carboplatin/therapeutic use ; Carcinoma, Non-Small-Cell Lung/immunology ; Cisplatin/therapeutic use ; Cisplatin/toxicity ; Cytotoxicity, Immunologic ; Humans ; Interleukin-2 Receptor alpha Subunit/immunology ; Lung Neoplasms/immunology ; Lung Neoplasms/pathology ; Lymphocyte Count ; Lymphocyte Depletion ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/pathology ; Lymphopenia/genetics ; Lymphopenia/immunology ; Mice ; Mice, Mutant Strains ; Mice, Transgenic ; Random Allocation ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/pathology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/pathology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/pathology ; Tumor Escape ; Tumor Microenvironment/immunology
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents, Alkylating ; Interleukin-2 Receptor alpha Subunit ; Carboplatin (BG3F62OND5) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2013-07-12
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1301317
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Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 28: Show issues

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Article: Novel therapies targeting signaling pathways in lung cancer.

Yagui-Beltrán, Adam / He, Biao / Raz, Dan / Kim, Jae / Jablons, David M

Thoracic surgery clinics

2006 Volume 16, Issue 4, Page(s) 379–96, vi

Abstract: Despite advances in chemotherapy, the prognosis for advanced non-small-cell lung cancer (NSCLC) remains dismal. Increasing understanding of the biological processes responsible for lung carcinogenesis has led to development of new therapeutic strategies ... ...

Abstract	Despite advances in chemotherapy, the prognosis for advanced non-small-cell lung cancer (NSCLC) remains dismal. Increasing understanding of the biological processes responsible for lung carcinogenesis has led to development of new therapeutic strategies targeting this disease at a molecular level. This article examines the molecular events believed to lead to cellular changes in lung cancer, and how knowledge of these is used to develop new agents used individually or in combination with available cytotoxic drugs to improve survival. Finally, it explores how a deeper understanding of the embryonic signaling pathways responsible for airway epithelial repair and tumorogenesis, such as Hedgehog (Hh), Notch, and Wingless (Wnt), can lead to the development of newer and more specific therapies for lung cancer.
MeSH term(s)	Cell Transformation, Neoplastic/genetics ; Genes, Tumor Suppressor ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Neovascularization, Pathologic/drug therapy ; Oncogenes/genetics ; Receptor, Epidermal Growth Factor/antagonists & inhibitors ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors ; Signal Transduction/drug effects
Chemical Substances	Receptor, Epidermal Growth Factor (EC 2.7.10.1) ; Receptors, Vascular Endothelial Growth Factor (EC 2.7.10.1)
Language	English
Publishing date	2006-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2149218-9
ISSN	1558-5069 ; 1547-4127
ISSN (online)	1558-5069
ISSN	1547-4127
DOI	10.1016/j.thorsurg.2006.07.001
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Article ; Online: Epigenetic alteration of the Wnt inhibitory factor-1 promoter occurs early in the carcinogenesis of Barrett's esophagus.

Clément, Geneviève / Guilleret, Isabelle / He, Biao / Yagui-Beltrán, Adam / Lin, Yu-Ching / You, Liang / Xu, Zhidong / Shi, Yihui / Okamoto, Junichi / Benhattar, Jean / Jablons, David

Cancer science

2007 Volume 99, Issue 1, Page(s) 46–53

Abstract: The role of Wnt antagonists in the carcinogenesis of esophageal adenocarcinoma (EAC) remains unclear. We hypothesized that downregulation of the Wnt inhibitory factor-1 (WIF-1) might be involved in the neoplastic progression of Barrett's esophagus (BE). ... ...

Abstract	The role of Wnt antagonists in the carcinogenesis of esophageal adenocarcinoma (EAC) remains unclear. We hypothesized that downregulation of the Wnt inhibitory factor-1 (WIF-1) might be involved in the neoplastic progression of Barrett's esophagus (BE). We analyzed the DNA methylation status of the WIF-1 promoter in normal, preneoplastic, and neoplastic samples from BE patients and in EAC cell lines. We investigated the role of WIF-1 on EAC cell growth and the chemosensitization of the cells to cisplatin. We found that silencing of WIF-1 correlated with promoter hypermethylation. EAC tissue samples showed higher levels of WIF-1 methylation compared to the matched normal epithelium. In addition, we found that WIF-1 hypermethylation was more frequent in BE samples from patients with EAC than in BE samples from patients who had not progressed to EAC. Restoration of WIF-1 in cell lines where WIF-1 was methylation-silenced resulted in growth suppression. Restoration of WIF-1 could sensitize the EAC cells to the chemotherapy drug cisplatin. Our results suggest that silencing of WIF-1 through promoter hypermethylation is an early and common event in the carcinogenesis of BE. Restoring functional WIF-1 might be used as a new targeted therapy for the treatment of this malignancy.
MeSH term(s)	Adaptor Proteins, Signal Transducing/biosynthesis ; Adaptor Proteins, Signal Transducing/genetics ; Adenocarcinoma/drug therapy ; Adenocarcinoma/genetics ; Adenocarcinoma/metabolism ; Adenocarcinoma/pathology ; Antineoplastic Agents/pharmacology ; Barrett Esophagus/drug therapy ; Barrett Esophagus/genetics ; Barrett Esophagus/metabolism ; Barrett Esophagus/pathology ; Cell Line, Tumor ; Cisplatin/pharmacology ; DNA Methylation ; Disease Progression ; Epigenesis, Genetic ; Esophageal Neoplasms/drug therapy ; Esophageal Neoplasms/genetics ; Esophageal Neoplasms/metabolism ; Esophageal Neoplasms/pathology ; Gene Silencing ; Humans ; Promoter Regions, Genetic ; Repressor Proteins/biosynthesis ; Repressor Proteins/genetics
Chemical Substances	Adaptor Proteins, Signal Transducing ; Antineoplastic Agents ; Repressor Proteins ; WIF1 protein, human ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2007-11-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1347-9032
ISSN (online)	1349-7006
ISSN	1347-9032
DOI	10.1111/j.1349-7006.2007.00663.x
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Article ; Online: Downregulation of EMX2 is associated with clinical outcomes in lung adenocarcinoma patients.

Okamoto, Junichi / Kratz, Johannes R / Hirata, Tomomi / Mikami, Iwao / Raz, Dan / Segal, Mark / Chen, Zhao / Zhou, Hai-Meng / Pham, Patrick / Li, Hui / Yagui-Beltran, Adam / Beltran, Adam / Ray, M Roshni / Koizumi, Kiyoshi / Shimizu, Kazuo / Jablons, David / He, Biao

Clinical lung cancer

2011 Volume 12, Issue 4, Page(s) 237–244

Abstract: Background: The 5-year survival rate for stage I non-small-cell lung cancer (NSCLC) of 50% to 70% indicates that our current staging methods do not adequately predict outcome. Empty spiracles homeobox 2 (EMX2) is a homeo-domain-containing transcription ... ...

Abstract	Background: The 5-year survival rate for stage I non-small-cell lung cancer (NSCLC) of 50% to 70% indicates that our current staging methods do not adequately predict outcome. Empty spiracles homeobox 2 (EMX2) is a homeo-domain-containing transcription factor that regulates a key developmental pathway known to promote lung tumorigenesis. This study assessed the significance of EMX2 as a prognostic biomarker in lung adenocarcinoma including bronchioloalveolar carcinoma (BAC). Patients and methods: 144 patients with lung adenocarcinoma undergoing surgical resection were studied. Quantitative real-time reverse transcriptase polymerase chain reaction and Immunohistochemistry were used to analyze EMX2 mRNA and protein expression, respectively. Association of EMX2 mRNA expression levels with clinical outcomes was evaluated using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model. Results: EMX2 mRNA expression was significantly downregulated in lung adenocarcinoma compared with matched adjacent normal tissue (P < .001). EMX2 protein expression was similarly found to be downregulated in lung adenocarcinoma. The EMX2-high mRNA expressing group had statistically significant better overall survival (OS) than the EMX2-low mRNA expressing group (P = .005). Subgroup analysis also demonstrated improved survival in stage I patients (P = .01) and patients with BAC (P = .03). Lastly, the EMX2-high mRNA expressing group had statistically significant better recurrence-free survival (RFS) than the EMX2-low mRNA expression group in patients with adenocarcinoma (P < .001). Conclusion: EMX2 expression is downregulated in lung adenocarcinoma. Low EMX2 mRNA expression is significantly associated with decreased OS and RFS in patients with lung adenocarcinoma, particularly with stage I disease and BAC.
MeSH term(s)	Adenocarcinoma/genetics ; Adenocarcinoma/secondary ; Adenocarcinoma/therapy ; Adenocarcinoma, Bronchiolo-Alveolar/genetics ; Adenocarcinoma, Bronchiolo-Alveolar/secondary ; Adenocarcinoma, Bronchiolo-Alveolar/therapy ; Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/secondary ; Carcinoma, Non-Small-Cell Lung/therapy ; Down-Regulation ; Female ; Follow-Up Studies ; Homeodomain Proteins/genetics ; Humans ; Lung/metabolism ; Lung/pathology ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Lung Neoplasms/therapy ; Male ; Middle Aged ; Neoplasm Staging ; Prospective Studies ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; Transcription Factors/genetics ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Homeodomain Proteins ; RNA, Messenger ; Transcription Factors ; empty spiracles homeobox proteins
Language	English
Publishing date	2011-04-24
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2145146-1
ISSN	1938-0690 ; 1525-7304
ISSN (online)	1938-0690
ISSN	1525-7304
DOI	10.1016/j.cllc.2011.03.025
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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