Myristoylated alanine-rich C-kinase substrate as a prognostic biomarker in human primary lung squamous cell carcinoma.
To identify novel biomarkers for the diagnosis and prognosis of human primary lung squamous cell carcinoma (SCC), we compared the spectrum of proteins expressed in SCC and in the adjacent non-cancer tissue, using QSTAR Elite liquid chromatography with tandem mass spectrometry (LC-MS/MS), coupled with iTRAQ technology. We identified 410 proteins differentially expressed in more than 75% of patients, and validated the expression of candidate target proteins by immunohistochemistry. Based on the results of LC-MS/MS, Ingenuity Pathway Analysis and immunohistochemical analyses, myristoylated alanine-rich C-kinase substrate (MARCKS) (upregulated 2.28-fold, p< 0.005) was selected as a potential biomarker of human lung SCC. In order to evaluate the association between patient prognosis and the expression of candidate biomarkers, univariate survival analysis was performed with disease-specific survival curves according to the Kaplan-Meier method, and differences in survival were assessed with the log-rank test. Immunohistochemical evaluation of MARCKS in 99 patients with lung SCC revealed a significant association between positive expression and poor prognosis compared with patients with negative expression (log-rank test; p=0.024). These results indicate that MARCKS may represent a potential biomarker for the prognosis of primary lung SCC.
Department of Thoracic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Shoji
S
Hanada
Anna
A
Kakehashi
Noritoshi
N
Nishiyama
Min
M
Wei
Shotaro
S
Yamano
Kyukwang
K
Chung
Hiroaki
H
Komatsu
Hidetoshi
H
Inoue
Shigefumi
S
Suehiro
Hideki
H
Wanibuchi
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D008297:Male; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008875:Middle Aged; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D015398:Signal Transduction
D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate
Lung cancer; proteomics; squamous cell carcinoma