RGD Reference Report - Discovery of new membrane-associated proteins overexpressed in small-cell lung cancer. - Rat Genome Database

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

Authors: Ocak, Sebahat  Friedman, David B  Chen, Heidi  Ausborn, Jamie A  Hassanein, Mohamed  Detry, Bruno  Weynand, Birgit  Aboubakar, Frank  Pilette, Charles  Sibille, Yves  Massion, Pierre P 
Citation: Ocak S, etal., J Thorac Oncol. 2014 Mar;9(3):324-36. doi: 10.1097/JTO.0000000000000090.
RGD ID: 126781753
Pubmed: PMID:24518087   (View Abstract at PubMed)
PMCID: PMC4028683   (View Article at PubMed Central)
DOI: DOI:10.1097/JTO.0000000000000090   (Journal Full-text)


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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GNAQHumanlung non-small cell carcinoma disease_progressionIEP  RGD 
GnaqRatlung non-small cell carcinoma disease_progressionISOGNAQ (Homo sapiens) RGD 
GnaqMouselung non-small cell carcinoma disease_progressionISOGNAQ (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gnaq  (G protein subunit alpha q)

Genes (Mus musculus)
Gnaq  (guanine nucleotide binding protein, alpha q polypeptide)

Genes (Homo sapiens)
GNAQ  (G protein subunit alpha q)


Additional Information