Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis, and tissue microarray validation.
Published version of a preprint
Abstract
PURPOSE: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap. EXPERIMENTAL DESIGN: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860). RESULTS: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate <1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup. CONCLUSIONS: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics.
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In two datasets of 55 and 196 non-small-cell lung cancer patients, there was no significant difference in OS between patients with high vs. low SLFN11 expression (HR = 1.60 and 1.16, p = 0.348 and 0.368, respectively).
“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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“The following datasets were obtained and analyzed: GSE37751 [10], GSE29013 [11], GSE37745 [12], GSE17260 [13], GSE32646 [14], and GSE63885 [15].”
Background
- Authors
- Botling, J., Edlund, K., Lohr, M., Hellwig, B., Holmberg, L., Lambe, M., Berglund, A., Ekman, S., Bergqvist, M., Pontén, F., König, A., Fernandes, O., Karlsson, M., Helenius, G., Karlsson, C., Rahnenführer, J., Hengstler, J. G., & Micke, P.
- Affiliations
- Uppsala University (SE)
- Corresponding author
- Micke, Patrick
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2013-01-01
- Volume
- 19
- Issue
- 1
- Pages
- 194-204
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2107296273
- Cited by
- 359
- References
- 47
- Citations by year
- 2026: 10 · 2025: 25 · 2024: 21 · 2023: 23 · 2022: 40 · 2021: 50 · 2020: 23 · 2019: 35 · 2018: 19 · 2017: 31 · 2016: 23 · 2015: 21 · 2014: 27 · 2013: 11
- FWCI
- 9.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Keywords
- non-small cell lung cancer, prognostic factors, CADM1, gene expression profiling, meta-analysis, survival, lung adenocarcinoma, immunohistochemistry, Cox proportional hazards model
- MeSH terms
- Cell Adhesion Molecule-1, Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Female, Humans, Immunoglobulins, Lung Neoplasms, Male, Middle Aged, Neoplasm Staging, Prognosis, Biomarkers, Tumor, Reproducibility of Results, Cell Adhesion Molecules, Gene Expression Regulation, Neoplastic, Cluster Analysis, Gene Expression Profiling
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