Proteomic profiles of human lung adeno and squamous cell carcinoma using super-SILAC and label-free quantification approaches.
Nonsmall cell lung cancer (NSCLC) accounts for 85% of lung cancers, and is subdivided into two major histological subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). There is an unmet need to further subdivide NSCLC according to distinctive molecular features that may be associated with responsiveness to therapies. Four primary tumor-derived xenograft proteomes (two-each ADC and SCC) were quantitatively compared by using a super-SILAC labeling approach together with ultrahigh-resolution MS. Proteins highly differentially expressed in the two subtypes were identified, including 30 that were validated in an independent cohort of 12 NSCLC primary tumor-derived xenograft tumors whose proteomes were quantified by an alternative, label-free shotgun MS methodology. The 30-protein signature contains metabolism enzymes including phosphoglycerate dehydrogenase, which is more highly expressed in SCC, as well as a comprehensive set of cytokeratins and other components of the epithelial barrier, which is therefore distinctly different between ADC and SCC. These results demonstrate the utility of the super-SILAC method for the characterization of primary tissues, and compatibility with datasets derived from different MS-based platforms. The validation of proteome signatures of NSCLC subtypes supports the further development and application of MS-based quantitative proteomics as a basis for precision classifications and treatments of tumors. All MS data have been deposited in the ProteomeXchange with identifier PXD000438 (http://proteomecentral.proteomexchange.org/dataset/PXD000438).
Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Wen
W
Zhang
Yuhong
Y
Wei
Vladimir
V
Ignatchenko
Lei
L
Li
Shingo
S
Sakashita
Nhu-An
NA
Pham
Paul
P
Taylor
Ming Sound
MS
Tsao
Thomas
T
Kislinger
Michael F
MF
Moran
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
D020543:Proteome
Biomedicine; Label-free; Lung cancer; Shotgun proteomics; Super-SILAC; Xenograft