Establishment of a multi-analyte serum biomarker panel to identify lymph node metastases in non-small cell lung cancer.
BACKGROUND
In non-small cell lung cancer (NSCLC), the presence of locoregional lymph node metastases remains the most important prognostic factor and significantly guides treatment regimens. Unfortunately, currently-available noninvasive staging modalities have limited accuracy. The objective of this study was to create a multianalyte blood test capable of discriminating a patient's true (pathologic) nodal status preoperatively.


METHODS
Pretreatment serum specimens collected from 107 NSCLC patients with localized disease were screened with 47 biomarkers implicated in disease presence or progression. Multivariate statistical algorithms were then used to identify the optimal combination of biomarkers for accurately discerning each patient's nodal status.


RESULTS
We identified 15 candidate biomarkers that met our criteria for statistical relevance in discerning a patient's preoperative nodal status. A 'random forest' classification algorithm was used with these parameters to define a 6-analyte panel, consisting of macrophage inflammatory protein-1alpha, carcinoembryonic antigen, stem cell factor, tumor necrosis factor-receptor I, interferon-gamma, and tumor necrosis factor-alpha, that was the optimum combination of biomarkers for identifying a patient's pathologic nodal status. A Classification and Regression Tree analysis was then created with this panel that was capable of correctly classifying 88% of the patients tested, relative to the pathologic assessments. This value is in contrast to our observed 85% classification rate using conventional clinical methods.


CONCLUSIONS
This study establishes a serum biomarker panel with efficacy in discerning preoperative nodal status. With further validation, this blood test may be useful for assessing nodal status (including occult disease) in NSCLC patients facing tumor resection therapy.
Borgia
Jeffrey A
JA
Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA. jeffrey_borgia@rush.edu
Basu
Sanjib
S
Faber
L Penfield
LP
Kim
Anthony W
AW
Coon
John S
JS
Kaiser-Walters
Kelly A
KA
Fhied
Cristina
C
Thomas
Sherene
S
Rouhi
Omid
O
Warren
William H
WH
Bonomi
Philip
P
Liptay
Michael J
MJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood / Q000145:classification*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011013:Pneumonectomy / Q000379:methods; D011237:Predictive Value of Tests; D011300:Preoperative Care; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate; D055815:Young Adult
D014408:Biomarkers, Tumor