Serum protein expression predicts recurrence in patients with early-stage lung cancer after resection.
BACKGROUND
Patients with early stage nonsmall-cell lung cancer who have undergone complete resection have a recurrence rate of approximately 50%, predominately due to the development of systemic metastases. This study is a prospective analysis of the expression of seven serum protein markers of invasion and metastasis, collected preoperatively (baseline) and serially after resection, to determine the relationship between marker expression and recurrence.


METHODS
Serum was collected from 196 patients with clinical stage I nonsmall-cell lung cancer who underwent resection over a 5-year period (1996 to 2000). Samples were drawn before resection and 1, 4, 6, 12, 18, and 24 months postoperatively. All patients were followed for at least 24 months or until death. Serum protein levels of vascular endothelial growth factor, hepatocyte growth factor), E-selectin, CD44, basic fibroblast growth factor, urokinase plasminogen activator, and urokinase plasminogen activator receptor were determined using enzyme-linked immunosorbent assay.


RESULTS
To date, 73 patients (37%) have demonstrated recurrence. Baseline levels of only 1 marker (CD44) correlated with pathologic stage (p = 0.02). Analysis of the serial samples demonstrated that recurrence was predicted (before clinical or radiographic determination) by decreasing levels of E-selectin (p = 0.002), increasing levels of CD44 (p = 0.001), and increasing levels of urokinase plasminogen activator receptor (p = 0.03).


CONCLUSIONS
This study demonstrates the potential to predict recurrence after resection in patients with early-stage nonsmall-cell lung cancer using a panel of serum protein markers. Early identification of patients with recurrence may improve the efficacy of systemic therapy.
D'Amico
Thomas A
TA
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. damic001@mc.duke.edu
Brooks
Kelli R
KR
Joshi
Mary-Beth Moore
MB
Conlon
Debbi
D
Herndon
James
J
Petersen
Rebecca P
RP
Harpole
David H
DH
D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology / Q000556:secondary* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000473:pathology / Q000556:secondary* / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000473:pathology / Q000556:secondary* / Q000601:surgery; D019040:E-Selectin / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D005500:Follow-Up Studies; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D018960:Hyaluronan Receptors / Q000097:blood; D015993:Life Tables; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000453:epidemiology; D009367:Neoplasm Staging; D011013:Pneumonectomy; D011184:Postoperative Period; D011237:Predictive Value of Tests; D011956:Receptors, Cell Surface / Q000097:blood; D055293:Receptors, Urokinase Plasminogen Activator; D016019:Survival Analysis; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D014408:Biomarkers, Tumor; D019040:E-Selectin; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D014568:Urokinase-Type Plasminogen Activator