UMMS Affiliation

Department of Molecular, Cell and Cancer Biology; Department of Pathology; Graduate School of Biomedical Sciences; School of Medicine; Senior Scholars Program

Publication Date


Document Type



Amino Acids, Peptides, and Proteins | Cancer Biology | Cells | Molecular Biology | Neoplasms | Oncology | Pathology | Respiratory Tract Diseases | Therapeutics


The 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.


Adenocarcinomas, Non-small cell lung cancer, Cytoplasmic staining, Squamous cell carcinomas, Nuclear staining, Membrane staining, Cell staining, Lung and intrathoracic tumors

Rights and Permissions

Copyright: © 2019 Piper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI of Published Version



PLoS One. 2019 Aug 8;14(8):e0220567. doi: 10.1371/journal.pone.0220567. eCollection 2019. Link to article on publisher's site

Journal/Book/Conference Title

PloS one


Andrew Piper participated in this study as a medical student in the Senior Scholars research program at the University of Massachusetts Medical School.

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.