Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Mar 20;18(1):310.
doi: 10.1186/s12885-018-4193-0.

The serum-based VeriStrat® test is associated with proinflammatory reactants and clinical outcome in non-small cell lung cancer patients

Mary Jo Fidler  1 , Cristina L Fhied  2 , Joanna Roder  3 , Sanjib Basu  4 , Selina Sayidine  2 , Ibtihaj Fughhi  1 , Mark Pool  2 , Marta Batus  1 , Philip Bonomi  1 , Jeffrey A Borgia  5   6   7
Affiliations

The serum-based VeriStrat® test is associated with proinflammatory reactants and clinical outcome in non-small cell lung cancer patients

Mary Jo Fidler et al. BMC Cancer. .

Abstract

Background: The VeriStrat test is a serum proteomic signature originally discovered in non-responders to second line gefitinib treatment and subsequently used to predict differential benefit from erlotinib versus chemotherapy in previously treated advanced non-small cell lung cancer (NSCLC). Multiple studies highlight the clinical utility of the VeriStrat test, however, the mechanistic connection between VeriStrat-poor classification and poor prognosis in untreated and previously treated patients is still an active area of research. The aim of this study was to correlate VeriStrat status with other circulating biomarkers in advanced NSCLC patients - each with respect to clinical outcomes.

Methods: Serum samples were prospectively collected from 57 patients receiving salvage chemotherapy and 70 non-EGFR mutated patients receiving erlotinib. Patients were classified as either VeriStrat good or poor based on the VeriStrat test. Luminex immunoassays were used to measure circulating levels of 102 distinct biomarkers implicated in tumor aggressiveness and treatment resistance. A Cox PH model was used to evaluate associations between biomarker levels and clinical outcome, whereas the association of VeriStrat classifications with biomarker levels was assessed via the Mann-Whitney Rank Sum test.

Results: VeriStrat was prognostic for outcome within the erlotinib treated patients (HR = 0.29, p < 0.0001) and predictive of differential treatment benefit between erlotinib and chemotherapy ((interaction HR = 0.25; interaction p = 0.0035). A total of 27 biomarkers out of 102 unique analytes were found to be significantly associated with OS (Cox PH p ≤ 0.05), whereas 16 biomarkers were found to be associated with PFS. Thrombospondin-2, C-reactive protein, TNF-receptor I, and placental growth factor were the analytes most highly associated with OS, all with Cox PH p-values ≤0.0001. VeriStrat status was found to be significantly associated with 23 circulating biomarkers (Mann-Whitney Rank Sum p ≤ 0.05), 6 of which had p < 0.001, including C-reactive protein, IL-6, serum amyloid A, CYFRA 21.1, IGF-II, osteopontin, and ferritin.

Conclusions: Strong associations were observed between survival and VeriStrat classifications as well as select circulating biomarkers associated with fibrosis, inflammation, and acute phase reactants as part of this study. The associations between these biomarkers and VeriStrat classification might have therapeutic implications for poor prognosis NSCLC patients, particularly with new immunotherapeutic treatment options.

Keywords: Biomarker; Erlotinib; Luminex; Non-small cell lung cancer (NSCLC); Serum; VeriStrat.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Institutional Review Board at Rush University Medical Center and all specimens were collected with written informed consent from all subjects enrolled.

Consent for publication

Not applicable.

Competing interests

All authors have no competing interests to disclose with exception of J.R., who is an employee at Biodesix, Incorporated.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Kaplan-Meier plot of OS by VeriStrat classification and treatment group
Fig. 2
Fig. 2
Box and whisker plots of biomarker levels in association with VeriStrat status
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Taguchi F, Solomon B, Gregorc V, Roder H, Gray R, Kasahara K, Nishio M, Brahmer J, Spreafico A, Ludovini V, et al. Mass spectrometry to classify non-small-cell lung cancer patients for clinical outcome after treatment with epidermal growth factor receptor tyrosine kinase inhibitors: a multicohort cross-institutional study. J Natl Cancer Inst. 2007;99(11):838–846. doi: 10.1093/jnci/djk195. - DOI - PubMed
    1. Amann JM, Lee JW, Roder H, Brahmer J, Gonzalez A, Schiller JH, Carbone DP. Genetic and proteomic features associated with survival after treatment with erlotinib in first-line therapy of non-small cell lung cancer in eastern cooperative oncology group 3503. J Thorac Oncol. 2010;5(2):169–178. doi: 10.1097/JTO.0b013e3181c8cbd9. - DOI - PMC - PubMed
    1. Carbone DP, Ding K, Roder H, Grigorieva J, Roder J, Tsao MS, Seymour L, Shepherd FA. Prognostic and predictive role of the VeriStrat plasma test in patients with advanced non-small-cell lung cancer treated with erlotinib or placebo in the NCIC clinical trials group BR.21 trial. J Thorac Oncol. 2012;7(11):1653–1660. doi: 10.1097/JTO.0b013e31826c1155. - DOI - PMC - PubMed
    1. Stinchcombe TE. The use of EGFR tyrosine kinase inhibitors in EGFR wild-type non-small-cell lung Cancer. Curr Treat Options in Oncol. 2016;17(4):18. doi: 10.1007/s11864-016-0394-4. - DOI - PubMed
    1. Wakelee H, Goldman JW, Gadgeel S, Camidge DR, Reckamp KL, Ou SI, Yu HA, Solomon B, Liu SV, Perol M, et al. PS01.66: biomarker stratification of outcomes of third-generation EGFR TKI therapy in patients with previously-treated advanced NSCLC: Topic: Medical Oncology. J Thorac Oncol. 2016;11(11S):S311–S312. doi: 10.1016/j.jtho.2016.09.101. - DOI - PubMed

Publication types

MeSH terms