A simple two-gene prognostic model for adenocarcinoma of the lung.
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.
Reed
Carolyn E
CE
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA. reedce@musc.edu
Graham
Amanda
A
Hoda
Rana S
RS
Khoor
Andras
A
Garrett-Mayer
Elizabeth
E
Wallace
Michael B
MB
Mitas
Michael
M
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015820:Cadherins / Q000032:analysis*; D002147:Calmodulin / Q000032:analysis*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D053539:Keratin-19 / Q000235:genetics*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; C488659:CALM2 protein, human; D015820:Cadherins; D002147:Calmodulin; D053539:Keratin-19