Lymphangiogenic Markers and Their Impact on Nodal Metastasis and Survival in Non-Small Cell Lung Cancer - A Structured Review with Meta-Analysis

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Abstract

Background

In non-small cell lung cancer (NSCLC), nodal metastasis is an adverse prognostic factor. Several mediating factors have been implied in the development of nodal metastases and investigated for predictive and prognostic properties in NSCLC. However, study results differ. In this structured review and meta-analysis we explore the published literature on commonly recognized pathways for molecular regulation of lymphatic metastasis in NSCLC.

Methods

A structured PubMed search was conducted for papers reporting on the expression of known markers of lymhangiogenesis in NSCLC patients. Papers of sufficient quality, presenting survival and/or correlation data were included.

Results

High levels of vascular endothelial growth factor C (VEGF-C, HR 1.57 95% CI 1.34–1.84) and high lymphatic vascular density (LVD, HR 1.84 95% CI 1.18–2.87) were significant prognostic markers of poor survival and high expression of VEGF-C, vascular endothelial growth factor receptor 3 (VEGFR3) and LVD was associated with lymph node metastasis in NSCLC.

Conclusion

Lymphangiogenic markers are prognosticators of survival and correlate with lymph node metastasis in NSCLC. Their exact role and clinical implications should be further elucidated.

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Most cited references 62

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Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

M Parmar, V. Torri, L. Stewart (1998)

Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.

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The International Epidemiology of Lung Cancer: geographical distribution and secular trends.

Danny R Youlden, Susanna M Cramb, Peter D Baade (2008)

This review presents the latest available international data for lung cancer incidence, mortality and survival, emphasizing the established causal relationship between smoking and lung cancer. In 2002, it was estimated that 1.35 million people throughout the world were diagnosed with lung cancer, and 1.18 million died of lung cancer-more than for any other type of cancer. There are some key differences in the epidemiology of lung cancer between more developed and less developed countries. In more developed countries, incidence and mortality rates are generally declining among males and are starting to plateau for females, reflecting previous trends in smoking prevalence. In contrast, there are some populations in less developed countries where increasing lung cancer rates are predicted to continue, due to endemic use of tobacco. A higher proportion of lung cancer cases are attributable to nonsmoking causes within less developed countries, particularly among women. Worldwide, the majority of lung cancer patients are diagnosed after the disease has progressed to a more advanced stage. Despite advances in chemotherapy, prognosis for lung cancer patients remains poor, with 5-year relative survival less than 14% among males and less than 18% among females in most countries. Given the increasing incidence of lung cancer in less developed countries and the current lack of effective treatment for advanced lung cancers, these results highlight the need for ongoing global tobacco reform to reduce the international burden of lung cancer.

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Language bias in randomised controlled trials published in English and German.

M. Egger, T Zellweger-Zähner, M. Schneider … (1997)

Some randomised controlled trials (RCTs) done in German-speaking Europe are published in international English-language journals and others in national German-language journals. We assessed whether authors are more likely to report trials with statistically significant results in English than in German. We studied pairs of RCT reports, matched for first author and time of publication, with one report published in German and the other in English. Pairs were identified from reports round in a manual search of five leading German-language journals and from reports published by the same authors in English found on Medline. Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors' identities, affiliations, and other characteristics of trial reports. Main study endpoints were selected by two investigators who were unaware of trial results. Our main outcome was the number of pairs of studies in which the levels of significance (shown by p values) were discordant. 62 eligible pairs of reports were identified but 19 (31%) were excluded because they were duplicate publications. A further three pairs (5%) were excluded because no p values were given. The remaining 40 pairs were analysed. Design characteristics and quality features were similar for reports in both languages. Only 35% of German-language articles, compared with 62% of English-language articles, reported significant (p < 0.05) differences in the main endpoint between study and control groups (p = 0.002 by McNemar's test). Logistic regression showed that the only characteristic that predicted publication in an English-language journal was a significant result. The odds ratio for publication of trials with significant results in English was 3.75 (95% CI 1.25-11.3). Authors were more likely to publish RCTs in an English-language journal if the results were statistically significant. English language bias may, therefore, be introduced in reviews and meta-analyses if they include only trials reported in English. The effort of the Cochrane Collaboration to identify as many controlled trials as possible, through the manual search of many medical journals published in different languages will help to reduce such bias.

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Author and article information

Contributors

Xin-Yuan Guan: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 25 August 2015

Publication date Collection: 2015

Volume: 10

Issue: 8

Electronic Location Identifier: e0132481

Affiliations

[1 ]Department of Oncology, University Hospital of North Norway, Tromso, Norway

[2 ]Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway

[3 ]Department of Community Medicine, UiT The Arctic University of Norway, Tromso, Norway

[4 ]Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway

[5 ]Institute of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway

The University of Hong Kong, CHINA

Author notes

Competing Interests: The authors have declared that no competing interests exist.

Analyzed the data: TKK TW EEP SMH. Wrote the paper: TD EEP SMH RMB LTB.

* E-mail: kilvaer@ 123456gmail.com

Article

Publisher ID: PONE-D-15-13674

DOI: 10.1371/journal.pone.0132481

PMC ID: 4549062

PubMed ID: 26305218

SO-VID: 9dc2747c-2de1-4f40-b403-2e11a395b938

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

History

Date received : 2 April 2015

Date accepted : 15 June 2015

Page count

Figures: 3, Tables: 3, Pages: 17

Funding

The authors have no support or funding to report.

Custom metadata

Data Availability As this article constitutes a meta-analysis, all data are available through already published and cited articles.

ScienceOpen disciplines: Uncategorized

Data availability:

ScienceOpen disciplines: Uncategorized

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Lymphangiogenic Markers and Their Impact on Nodal Metastasis and Survival in Non-Small Cell Lung Cancer - A Structured Review with Meta-Analysis

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Abstract

Background

Methods

Results

Conclusion

Related collections

PLOS Climate

Most cited references 62

Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

The International Epidemiology of Lung Cancer: geographical distribution and secular trends.

Language bias in randomised controlled trials published in English and German.

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Contributors

Journal

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Cited by 5

Most referenced authors 1,252