Insulin Receptor Substrate-1 (IRS-1) and IRS-2 expression levels are associated with prognosis in non-small cell lung cancer (NSCLC)
AuthorsPiper, Andrew J.
Clark, Jennifer L.
Mercado-Matos, Jose R.
Matthew-Onabanjo, Asia N.
Shaw, Leslie M.
UMass Chan AffiliationsSenior Scholars Program
School of Medicine
Graduate School of Biomedical Sciences
Department of Pathology
Department of Molecular, Cell and Cancer Biology
Non-small cell lung cancer
Squamous cell carcinomas
Lung and intrathoracic tumors
Amino Acids, Peptides, and Proteins
Respiratory Tract Diseases
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AbstractThe insulin-like growth factor-1 (IGF-1) signaling pathway has been implicated in non-small cell lung cancer (NSCLC) outcomes and resistance to targeted therapies. However, little is known regarding the molecular mechanisms by which this pathway contributes to the biology of NSCLC. The insulin receptor substrate (IRS) proteins are cytoplasmic adaptor proteins that signal downstream of the IGF-1R and determine the functional outcomes of this signaling pathway. In this study, we assessed the expression patterns of IRS-1 and IRS-2 in NSCLC to identify associations between IRS-1 and IRS-2 expression levels and survival outcomes in the two major histological subtypes of NSCLC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). High IRS-2 expression was significantly associated with decreased overall survival in adenocarcinoma (ADC) patients, whereas low IRS-1 cytoplasmic expression showed a trend toward association with decreased overall survival in squamous cell carcinoma (SCC) patients. Tumors with low IRS-1 and high IRS-2 expression were found to be associated with poor outcomes in ADC and SCC, indicating a potential role for IRS-2 in the aggressive behavior of NSCLC. Our results suggest distinct contributions of IRS-1 and IRS-2 to the biology of ADC and SCC that impact disease progression.
PLoS One. 2019 Aug 8;14(8):e0220567. doi: 10.1371/journal.pone.0220567. eCollection 2019. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/41176
Andrew Piper participated in this study as a medical student in the Senior Scholars research program at the University of Massachusetts Medical School.