Development and Validation of a Plasma Biomarker Panel for Discerning Clinical Significance of Indeterminate Pulmonary Nodules

Abstract

We developed a seven-analyte plasma biomarker panel able to identify benign nodules, otherwise deemed indeterminate, with a high degree of accuracy. This panel may have clinical utility in risk-stratifying screen-detected lung nodules, decrease unnecessary follow-up imaging or invasive procedures, and potentially avoid unnecessary morbidity, mortality, and health care costs.

Angiogenesis Biomarkers May Be Useful in the Management of Patients With Indeterminate Pulmonary Nodules

“…Development of a plasma-based multi-analyte classification panel was conducted using 31 patients with benign nodules and 59 patients with stage I NSCLC, as previously described [11,12]. A unique validation cohort from Mayo Clinic, consisting of patients with benign nodules (n ¼ 61) and those with pathologically proven stage I lung cancer (n ¼ 19) was employed to test the classification panel.…”

“…This includes all patients who received anatomic resections and wedge resections for diagnosis. A second cohort from Rush University Medical Center with benign pathology were also accrued from an internal LDCT screening trial (n ¼ 18) in which all cases were followed for a minimum of 2 years to ensure the absence of a malignancy, as previously described [11,12]. Finally, specimens from additional patients with either benign disease (n ¼ 51) or with pathologically diagnosed stage I lung cancer (n ¼ 48) that matched the inclusion criteria above were obtained from Mayo Clinic (Rochester, MN) for our biomarker performance evaluation.…”

“…The objective of this study is to investigate if serum biomarkers of angiogenesis are capable of distinguishing stage I NSCLC from benign nodules in high-risk individuals with positive radiography. In addition, we also evaluate the ability of these biomarkers to improve the performance of our previously reported multi-analyte lung cancer detection panel [11,12].…”

Value of circulating insulin-like growth factor–associated proteins for the detection of stage I non–small cell lung cancer

“…14 The performance of several of the iterations of the random forest analysis is provided as Table E2, with iteration 5 providing the optimal performance characteristics from a 7-analyte panel. This new 7-analyte classification panel was composed of interleukin (IL)-6, IL-10, IL-1 receptor antagonist, stromal cell-derived factor-1a þ b, IGFBP-4, IGFBP-5, and IGF-2.…”

“…13 Here, we investigate the potential value of these IGF-related factors to distinguish earlystage NSCLC from cases of benign disease in high-risk individuals with positive radiography. Further, we also evaluate the value of these biomarkers as a means to improve upon the performance of our multivariate plasma test for this purpose 14 and validated this refined panel against a second, independent cohort from the Mayo Clinic.…”