Pierre Massion
Faculty Member
Last active: 1/11/2018

Discovery of new membrane-associated proteins overexpressed in small-cell lung cancer.

Ocak S, Friedman DB, Chen H, Ausborn JA, Hassanein M, Detry B, Weynand B, Aboubakar F, Pilette C, Sibille Y, Massion PP
J Thorac Oncol. 2014 9 (3): 324-36

PMID: 24518087 · PMCID: PMC4028683 · DOI:10.1097/JTO.0000000000000090

INTRODUCTION - Small-cell lung cancer (SCLC) is the most aggressive subtype of lung cancer, with no early detection strategy or targeted therapy currently available. We hypothesized that difference gel electrophoresis (DIGE) may identify membrane-associated proteins (MAPs) specific to SCLC, advance our understanding of SCLC biology, and discover new biomarkers of SCLC.

METHODS - MAP lysates were prepared from three SCLCs, three non-small-cell lung cancers, and three immortalized normal bronchial epithelial cell lines and coanalyzed by DIGE. Subsequent protein identification was performed by mass spectrometry. Proteins were submitted to Ingenuity Pathway Analysis. Candidate biomarkers were validated by Western blotting (WB) and immunohistochemistry (IHC).

RESULTS - Principal component analysis on the global DIGE data set demonstrated that the four replicates derived from each of the nine cell lines clustered closely, as did samples within the same histological group. One hundred thirty-seven proteins were differentially expressed in SCLC compared with non-small-cell lung cancer and immortalized normal bronchial epithelial cells. These proteins were overrepresented in cellular/tissue morphology networks. Dihydropyrimidinase-related protein 2, guanine nucleotide-binding protein alpha-q, laminin receptor 1, pontin, and stathmin 1 were selected as candidate biomarkers among MAPs overexpressed in SCLC. Overexpression of all candidates but RSSA in SCLC was verified by WB and/or IHC on tissue microarrays. These proteins were significantly associated with SCLC histology and survival in univariables analyses.

CONCLUSION - DIGE analysis of a membrane-associated subproteome discovered overexpression of dihydropyrimidinase-related protein 2, guanine nucleotide-binding protein alpha-q, RUVB1, and stathmin 1 in SCLC. Results were verified by WB and/or IHC in primary tumors, suggesting that investigating their functional relevance in SCLC progression is warranted. Association with survival requires further validation in larger clinical data sets.

MeSH Terms (21)

Adenocarcinoma Aged Biomarkers, Tumor Blotting, Western Bronchi Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Cells, Cultured Electrophoresis, Gel, Two-Dimensional Female Humans Immunoenzyme Techniques Lung Neoplasms Male Membrane Proteins Middle Aged Neoplasm Staging Prognosis Small Cell Lung Carcinoma Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Survival Rate

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