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

研究成果: Article査読

336 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)4417-4424
ページ数8
ジャーナルJournal of Clinical Oncology
28
29
DOI
出版ステータスPublished - 2010 10 10
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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