Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer

Chang Qi Zhu, Keyue Ding, Dan Strumpf, Barbara A. Weir, Matthew Meyerson, Nathan Pennell, Roman K. Thomas, Katsuhiko Naoki, Christine Ladd-Acosta, Ni Liu, Melania Pintilie, Sandy Der, Lesley Seymour, Igor Jurisica, Frances A. Shepherd, Ming Sound Tsao

Research output: Contribution to journalArticle

308 Citations (Scopus)

Abstract

Purpose: The JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non-small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT. Patients and Methods: Gene expression profiling was conducted on mRNA from 133 frozen JBR.10 tumor samples (62 observation [OBS], 71 ACT). The minimum gene set that was selected for the greatest separation of good and poor prognosis patient subgroups in OBS patients was identified. The prognostic value of this gene signature was tested in four independent published microarray data sets and by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR). Results: A 15-gene signature separated OBS patients into high-risk and low-risk subgroups with significantly different survival (hazard ratio [HR], 15.02; 95% CI, 5.12 to 44.04; P < .001; stage I HR, 13.31; P < .001; stage II HR, 13.47; P < .001). The prognostic effect was verified in the same 62 OBS patients where gene expression was assessed by qPCR. Furthermore, it was validated consistently in four separate microarray data sets (total 356 stage IB to II patients without adjuvant treatment) and additional JBR.10 OBS patients by qPCR (n = 19). The signature was also predictive of improved survival after ACT in JBR.10 high-risk patients (HR, 0.33; 95% CI, 0.17 to 0.63; P = .0005), but not in low-risk patients (HR, 3.67; 95% CI, 1.22 to 11.06; P = .0133; interaction P < .001). Significant interaction between risk groups and ACT was verified by qPCR. Conclusion: This 15-gene expression signature is an independent prognostic marker in early-stage, completely resected NSCLC, and to our knowledge, is the first signature that has demonstrated the potential to select patients with stage IB to II NSCLC most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine.

Original languageEnglish
Pages (from-to)4417-4424
Number of pages8
JournalJournal of Clinical Oncology
Volume28
Issue number29
DOIs
Publication statusPublished - 2010 Oct 10

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer'. Together they form a unique fingerprint.

  • Cite this

    Zhu, C. Q., Ding, K., Strumpf, D., Weir, B. A., Meyerson, M., Pennell, N., Thomas, R. K., Naoki, K., Ladd-Acosta, C., Liu, N., Pintilie, M., Der, S., Seymour, L., Jurisica, I., Shepherd, F. A., & Tsao, M. S. (2010). Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer. Journal of Clinical Oncology, 28(29), 4417-4424. https://doi.org/10.1200/JCO.2009.26.4325