Expression and Clinical Significance of Prohibitin in Primary Lung Squamous Cell Carcinoma.
Feng Guo, Kenzo Hiroshima, Takeshi Tomonaga, Fumio Nomura, Osamu Matsubara, Yukio Nakatani. Chiba University Graduate School of Medicine, Japan; Tokyo Women's Medical University Yachiyo Medical Center, Chiba, Japan; National Institute of Biomedical Innovation, Osaka, Japan; National Defense Medical College, Tokorozawa, Japan
Background: Lung cancer is the leading cause of cancer death for both man and women in the world. Studying the carcinogenesis of lung squamous cell carcinoma with proteomic approaches may identify carcinogenesis-associated proteins. The purpose of the study is to discover potential biomarkers for diagnosis, treatment and prevention of the lung squamous cell carcinoma by using proteome-based approaches.
Design: Protein samples from 10 paired lung squamous cell carcinoma (SqCC) tissues and noncancerous tissues were compared by fluorescent 2-D differential gel electrophoresis (2-D DIGE) .Validation of a candidate biomarker was carried out with Western blotting and immunohistochemistry analysis of 71 cases of lung SqCC. The immunostaining in tissue sections was divided into high and low expressions based on the intensity (1+ to 3+) and proportion (<40%, >40%) of positive cells. The correlation between PHB expression and clinicopathological indicators of lung SqCC was determined by using x2 test. Kaplan-Meier methods were used to compare survival rates. Cox proportional hazards models were used to identify independently significant variables.
Results: Thirty-six proteins whose expression altered significantly in the tumor tissue were identified by mass spectrometry. Among them, a 30-kDa protein prohibitin (PHB) was up-regulated in lung SqCC, which was confirmed by immunoblotting. In immunohistochemistry, high expression of cytoplasmic PHB was seen in 41 out of 71 SqCC patients, and was associated with UICC classification of tumor grade (p=0.011), tumor size (p=0.03), lymph node metastasis (P=0.01) and pathological stages (p=0.002). During the median 56 months of follow-up, patients who had the high expression of PHB had low over-all(P=0.008) and disease-free survival rates (P=0.034) by Univariate analysis. Multivariate analysis indicated that PHB was an independent prognostic factor for SqCC (P=0.04).
Conclusions: The expression of PHB may play an important role in the development and progression of human squamous cell carcinoma. PHB is likely to be a clinical prognostic biomarker and may be a potential therapeutic target for lung cancer.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 252, Tuesday Afternoon