JTCS Click here to go to SJM website.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Carolyn E. Reed
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Reed, C. E.
Right arrow Articles by Mitas, M.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Reed, C. E.
Right arrow Articles by Mitas, M.
Related Collections
Right arrow Lung - cancer
Right arrow Molecular biology
Right arrow Lung - basic science
Right arrowRelated Article

J Thorac Cardiovasc Surg 2008;135:627-634
© 2008 The American Association for Thoracic Surgery

General Thoracic Surgery

A simple two-gene prognostic model for adenocarcinoma of the lung

Carolyn E. Reed, MDa,*, Amanda Graham, MSa, Rana S. Hoda, MDb, Andras Khoor, MDd, Elizabeth Garrett-Mayer, PhDc, Michael B. Wallace, MDe, Michael Mitas, PhDa

a Department of Surgery, Medical University of South Carolina, Charleston, SC
b Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC
c Department of Biostatics, Bioinformatics & Epidemiology, Medical University of South Carolina, Charleston, SC
d Department of Laboratory Medicine & Pathology, Mayo Clinic, Jacksonville, Fla
e Division of Gastroenterology & Hepatology, Mayo Clinic, Jacksonville, Fla

Received for publication April 23, 2007; revisions received September 3, 2007; accepted for publication October 26, 2007.

* Address for reprints: Carolyn E. Reed, MD, Medical University of South Carolina, 96 Jonathan Lucas St, 418 CSB, Charleston, SC 29425. (Email: reedce{at}musc.edu).

Objective: We hypothesized that clinical outcome of resected early-stage adenocarcinoma of the lung can be predicted by the expression of a few critically important genes as measured by quantitative real-time reverse-transcriptase polymerase chain reaction in formalin-fixed paraffin-embedded primary tumors.

Methods: Twenty-two prognostic genes for the metastatic phenotype were identified through complementary DNA microarray analysis of 4 cancer cell lines and bioinformatics analysis. Expression levels of a subset of these genes (n = 13) were measured by real-time time reverse-transcriptase polymerase chain reaction in formalin-fixed paraffin-embedded primary adenocarcinoma from patients whose disease recurred within 2 years (n = 9) and in patients who did not have a recurrence (n = 11). Receiver operating characteristic curves were analyzed to establish prognostic values of single genes. The most informative gene was combined with the remaining genes to determine whether there was a particular pair(s) that yielded high diagnostic accuracy. A small validation study was performed.

Results: Receiver operating characteristic curve analysis of the single genes revealed that high expression of CK19 was associated with nonrecurrence (area under the curve = 0.859, confidence interval = 0.651–0.970). The CK19/EpCAM2 gene ratio had the most reproducible prognostic accuracy, followed by the CK19/P-cadherin ratio. A Kaplan–Meier survival analysis generated from the CK19/EpCAM2 ratio resulted in highly significant curves as a function of marker positivity (P = .0007; hazard ratio = 10.7). Significance declined but was maintained in the validation study.

Conclusions: This preliminary study provides evidence that the CK19/EpCAM2 and/or CK19/P-cadherin ratio(s) may be a simple and accurate prognostic indicator of clinical outcome in early-stage adenocarcinoma of the lung. If further validation studies from large patient cohorts confirm the results, adjuvant therapy could be targeted to this high-risk group.

Abbreviations and Acronyms AUC = area under the curve; cDNA = complementary DNA; CI = confidence interval; cRNA = complementary RNA; Ct = cycle of threshold; NSCLC = non–small cell lung cancer; RT-PCR = reverse-transcription polymerase chain reaction


Related Article

Discussion
J. Thorac. Cardiovasc. Surg. 2008 135: 633-634. [Extract] [Full Text] [PDF]





HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS
Copyright © 2008 by The American Association for Thoracic Surgery.