Affiliations: [a] Department of Thoracic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan | [b] Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan
Correspondence:
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Corresponding author: Noritoshi Nishiyama, Department of Thoracic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. Tel.: +81 6 6645 3841; Fax: +81 6 6646 6057; E-mail: m1364552@msic.med.osaka-cu.ac.jp.
Abstract: 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.
