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Robust gene expression signature from formalin-fixed paraffin-embedded samples predicts prognosis of non-small-cell lung cancer patients.
Open accessPublished version of a preprint
Abstract
PURPOSE: The requirement of frozen tissues for microarray experiments limits the clinical usage of genome-wide expression profiling by using microarray technology. The goal of this study is to test the feasibility of developing lung cancer prognosis gene signatures by using genome-wide expression profiling of formalin-fixed paraffin-embedded (FFPE) samples, which are widely available and provide a valuable rich source for studying the association of molecular changes in cancer and associated clinical outcomes. EXPERIMENTAL DESIGN: We randomly selected 100 Non-Small-Cell lung cancer (NSCLC) FFPE samples with annotated clinical information from the UT-Lung SPORE Tissue Bank. We microdissected tumor area from FFPE specimens and used Affymetrix U133 plus 2.0 arrays to attain gene expression data. After strict quality control and analysis procedures, a supervised principal component analysis was used to develop a robust prognosis signature for NSCLC. Three independent published microarray datasets were used to validate the prognosis model. RESULTS: This study showed that the robust gene signature derived from genome-wide expression profiling of FFPE samples is strongly associated with lung cancer clinical outcomes and can be used to refine the prognosis for stage I lung cancer patients, and the prognostic signature is independent of clinical variables. This signature was validated in several independent studies and was refined to a 59-gene lung cancer prognosis signature. CONCLUSIONS: We conclude that genome-wide profiling of FFPE lung cancer samples can identify a set of genes whose expression level provides prognostic information across different platforms and studies, which will allow its application in clinical settings.
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“In two datasets of 55 and 196 non-small-cell lung cancer patients [11, 12], there was no significant differences in OS between patients with high vs. low SLFN11 expression (HR = 1.60 and 1.16, p = 0.348 and 0.368, respectively) (Fig 3B and 3C).”
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Novel Therapeutic Strategies in Lung Cancer
Kurtyka, C. A. (2014) · Digital Commons - University of South Florida (University of South Florida)
Metadata
- Authors
- Xie, Y., Xiao, G., Coombes, K. R., Behrens, C., Solis, L. M., Raso, G., Girard, L., Erickson, H. S., Roth, J., Heymach, J. V., Moran, C., Danenberg, K., Minna, J. D., & Wistuba, I. I.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Authors' Affiliations: Departments of 1Clinical Sciences, 2Simmons Cancer Center, 3Internal Medicine, 4Pharmacology, and 5Hamon Center for Therapeutic Oncology Research, The University of Texas Southwestern Medical Center, Dallas; Departments of 6Bioinformatics and Computational Biology, 7Thoracic/Head and Neck Medical Oncology, 8Pathology and 9Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas; and 10Response Genetics, Inc., Los Angeles, California
- Corresponding author
- Wistuba, Ignacio I.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2011-09-01
- Volume
- 17
- Issue
- 17
- Pages
- 5705-5714
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC3166982
- OpenAlex
- W2167736999
- Cited by
- 162
- References
- 51
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 4 · 2023: 10 · 2022: 24 · 2021: 13 · 2020: 11 · 2019: 12 · 2018: 5 · 2017: 13 · 2016: 9 · 2015: 11 · 2014: 14 · 2013: 14 · 2012: 10
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R33DA027592, R21DA027592)
- National Cancer Institute (CA-16672, (P50-CA70907, R01CA152301, P50CA070907, P30CA016672)
- National Center for Research Resources (UL1RR024982)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- non-small cell lung cancer, prognostic gene signature, formalin-fixed paraffin-embedded tissue, gene expression profiling, tumor microdissection, stage I lung cancer, prognostic model validation
- MeSH terms
- Carcinoma, Non-Small-Cell Lung, Female, Formaldehyde, Humans, Lung Neoplasms, Male, Prognosis, Paraffin Embedding, Tissue Fixation, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling
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