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

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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
Externally publishedYes

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Adjuvant Chemotherapy
Non-Small Cell Lung Carcinoma
Cisplatin
Genes
Observation
Survival
Gene Expression Profiling
Reverse Transcriptase Polymerase Chain Reaction
Transcriptome
vinorelbine
Gene Expression
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Zhu, C. Q., Ding, K., Strumpf, D., Weir, B. A., Meyerson, M., Pennell, N., ... 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

Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer. / Zhu, Chang Qi; Ding, Keyue; Strumpf, Dan; Weir, Barbara A.; Meyerson, Matthew; Pennell, Nathan; Thomas, Roman K.; Naoki, Katsuhiko; Ladd-Acosta, Christine; Liu, Ni; Pintilie, Melania; Der, Sandy; Seymour, Lesley; Jurisica, Igor; Shepherd, Frances A.; Tsao, Ming Sound.

In: Journal of Clinical Oncology, Vol. 28, No. 29, 10.10.2010, p. 4417-4424.

Research output: Contribution to journalArticle

Zhu, CQ, Ding, K, Strumpf, D, Weir, BA, Meyerson, M, Pennell, N, Thomas, RK, Naoki, K, Ladd-Acosta, C, Liu, N, Pintilie, M, Der, S, Seymour, L, Jurisica, I, Shepherd, FA & Tsao, MS 2010, 'Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer', Journal of Clinical Oncology, vol. 28, no. 29, pp. 4417-4424. https://doi.org/10.1200/JCO.2009.26.4325
Zhu, Chang Qi ; Ding, Keyue ; Strumpf, Dan ; Weir, Barbara A. ; Meyerson, Matthew ; Pennell, Nathan ; Thomas, Roman K. ; Naoki, Katsuhiko ; Ladd-Acosta, Christine ; Liu, Ni ; Pintilie, Melania ; Der, Sandy ; Seymour, Lesley ; Jurisica, Igor ; Shepherd, Frances A. ; Tsao, Ming Sound. / Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 29. pp. 4417-4424.
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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.",
author = "Zhu, {Chang Qi} and Keyue Ding and Dan Strumpf and Weir, {Barbara A.} and Matthew Meyerson and Nathan Pennell and Thomas, {Roman K.} and Katsuhiko Naoki and Christine Ladd-Acosta and Ni Liu and Melania Pintilie and Sandy Der and Lesley Seymour and Igor Jurisica and Shepherd, {Frances A.} and Tsao, {Ming Sound}",
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T1 - Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer

AU - Zhu, Chang Qi

AU - Ding, Keyue

AU - Strumpf, Dan

AU - Weir, Barbara A.

AU - Meyerson, Matthew

AU - Pennell, Nathan

AU - Thomas, Roman K.

AU - Naoki, Katsuhiko

AU - Ladd-Acosta, Christine

AU - Liu, Ni

AU - Pintilie, Melania

AU - Der, Sandy

AU - Seymour, Lesley

AU - Jurisica, Igor

AU - Shepherd, Frances A.

AU - Tsao, Ming Sound

PY - 2010/10/10

Y1 - 2010/10/10

N2 - 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.

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