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Expression of PAM50 Genes in Lung Cancer: Evidence that Interactions between Hormone Receptors and HER2/HER3 Contribute to Poor Outcome
- Source :
- Neoplasia (New York, N.Y.), Neoplasia: An International Journal for Oncology Research, Vol 17, Iss 11, Pp 817-825 (2015)
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- Non–small cell lung cancers (NSCLCs) frequently express estrogen receptor (ER) β, and estrogen signaling is active in many lung tumors. We investigated the ability of genes contained in the prediction analysis of microarray 50 (PAM50) breast cancer risk predictor gene signature to provide prognostic information in NSCLC. Supervised principal component analysis of mRNA expression data was used to evaluate the ability of the PAM50 panel to provide prognostic information in a stage I NSCLC cohort, in an all-stage NSCLC cohort, and in The Cancer Genome Atlas data. Immunohistochemistry was used to determine status of ERβ and other proteins in lung tumor tissue. Associations with prognosis were observed in the stage I cohort. Cross-validation identified seven genes that, when analyzed together, consistently showed survival associations. In pathway analysis, the seven-gene panel described one network containing the ER and progesterone receptor, as well as human epidermal growth factor receptor (HER)2/HER3 and neuregulin-1. NSCLC cases also showed a significant association between ERβ and HER2 protein expression. Cases positive for HER2 expression were more likely to express HER3, and ERβ-positive cases were less likely to be both HER2 and HER3 negative. Prognostic ability of genes in the PAM50 panel was verified in an ERβ-positive cohort representing all NSCLC stages. In The Cancer Genome Atlas data sets, the PAM50 gene set was prognostic in both adenocarcinoma and squamous cell carcinoma, whereas the seven-gene panel was prognostic only in squamous cell carcinoma. Genes in the PAM50 panel, including those linking ER and HER2, identify lung cancer patients at risk for poor outcome, especially among ERβ-positive cases and squamous cell carcinoma.
- Subjects :
- Male
Cancer Research
Lung Neoplasms
Receptor, ErbB-3
ER, estrogen receptor
DFS, disease-free survival
Receptor, ErbB-2
HER3, human epidermal growth factor receptor 3
Estrogen receptor
Bioinformatics
Cohort Studies
0302 clinical medicine
NSCLC, non–small cell lung cancer
Carcinoma, Non-Small-Cell Lung
HER2, human epidermal growth factor receptor 2
PGR, progesterone receptor
0303 health sciences
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
PFS, progression-free survival
3. Good health
Gene Expression Regulation, Neoplastic
Survival Rate
Treatment Outcome
030220 oncology & carcinogenesis
Adenocarcinoma
Female
IHC, immunohistochemistry
Protein Binding
Biology
lcsh:RC254-282
Article
OS, overall survival
FFPE, formalin-fixed, paraffin embedded
03 medical and health sciences
Breast cancer
Progesterone receptor
medicine
Carcinoma
Estrogen Receptor beta
Humans
PAM50, prediction analysis of microarray 50 gene set
Lung cancer
Estrogen receptor beta
Aged
IPA, Ingenuity Pathway Analysis
030304 developmental biology
PCA, principal component analysis
Gene signature
medicine.disease
HR, hazard ratio
Tissue Array Analysis
Cancer research
TCGA, The Cancer Genome Atlas
Subjects
Details
- ISSN :
- 14765586
- Volume :
- 17
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Neoplasia
- Accession number :
- edsair.doi.dedup.....f7b0139dba31fb27192eec003141e18b
- Full Text :
- https://doi.org/10.1016/j.neo.2015.11.002