Universität zu Köln

Zhu, Chang-Qi, Ding, Keyue, Strumpf, Dan, Weir, Barbara A., Meyerson, Matthew ORCID: 0000-0002-9133-8108, Pennell, Nathan ORCID: 0000-0002-1458-0064, Thomas, Roman K., Naoki, Katsuhiko ORCID: 0000-0002-9637-1388, Ladd-Acosta, Christine, Liu, Ni, Pintilie, Melania, Der, Sandy, Seymour, Lesley, Jurisica, Igor, Shepherd, Frances A. and Tsao, Ming-Sound (2010). Prognostic and Predictive Gene Signature for Adjuvant Chemotherapy in Resected Non-Small-Cell Lung Cancer. J. Clin. Oncol., 28 (29). S. 4417 - 4425. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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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. J Clin Oncol 28:4417-4424. (C) 2010 by American Society of Clinical Oncology

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zhu, Chang-Qi UNSPECIFIED UNSPECIFIED UNSPECIFIED Ding, Keyue UNSPECIFIED UNSPECIFIED UNSPECIFIED Strumpf, Dan UNSPECIFIED UNSPECIFIED UNSPECIFIED Weir, Barbara A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyerson, Matthew UNSPECIFIED orcid.org/0000-0002-9133-8108 UNSPECIFIED Pennell, Nathan UNSPECIFIED orcid.org/0000-0002-1458-0064 UNSPECIFIED Thomas, Roman K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Naoki, Katsuhiko UNSPECIFIED orcid.org/0000-0002-9637-1388 UNSPECIFIED Ladd-Acosta, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Ni UNSPECIFIED UNSPECIFIED UNSPECIFIED Pintilie, Melania UNSPECIFIED UNSPECIFIED UNSPECIFIED Der, Sandy UNSPECIFIED UNSPECIFIED UNSPECIFIED Seymour, Lesley UNSPECIFIED UNSPECIFIED UNSPECIFIED Jurisica, Igor UNSPECIFIED UNSPECIFIED UNSPECIFIED Shepherd, Frances A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tsao, Ming-Sound UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-494337
DOI:	10.1200/JCO.2009.26.4325
Journal or Publication Title:	J. Clin. Oncol.
Volume:	28
Number:	29
Page Range:	S. 4417 - 4425
Date:	2010
Publisher:	AMER SOC CLINICAL ONCOLOGY
Place of Publication:	ALEXANDRIA
ISSN:	1527-7755
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXPRESSION SIGNATURES; SQUAMOUS-CELL; P53 PROTEIN; SURVIVAL; ADENOCARCINOMA; MDM2; DEPENDENCE Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49433