Decreased GRP78 Protein Expression is a Potential Prognostic Marker of Oral Squamous Cell Carcinoma in Taiwan

Huang, Tze-Ta; Chen, Jeff Yi-Fu; Tseng, Chih-En; Su, Yu-Chieh; Ho, Hsu-Chueh; Lee, Moon-Sing; Chang, Chiou-Tuz; Wong, Yong-Kie; Chen, Hau-Ren

doi:10.1016/S0929-6646(10)60060-5

« Previous Next »Journal of the Formosan Medical Association
Volume 109, Issue 5 , Pages 326-337, May 2010

Decreased GRP78 Protein Expression is a Potential Prognostic Marker of Oral Squamous Cell Carcinoma in Taiwan

Tze-Ta Huang
- Dental Department, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualian, Taiwan
Jeff Yi-Fu Chen
- Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan
Chih-En Tseng
- Department of Pathology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualian, Taiwan
Yu-Chieh Su
- Division of Hematology-Oncology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualian, Taiwan
Hsu-Chueh Ho
- Department of Otolaryngology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualian, Taiwan
Moon-Sing Lee
- Division of Radiotherapy and Radiooncology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualian, Taiwan
Chiou-Tuz Chang
- Dental Department, Taichung Veterans General Hospital, Taichung, Taiwan
Yong-Kie Wong
- Dental Department, Taichung Veterans General Hospital, Taichung, Taiwan
Hau-Ren Chen
- Department of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Chiayi, Taiwan
- Correspondence to: Dr Hau-Ren Chen, Department of Life Science, Institute of Molecular Biology, and Institute of Biomedical Science, National Chung Cheng University, 168 University Road, Min-Hsiung, Chia-Yi, Taiwan

Received 10 June 2008; received in revised form 16 November 2008; accepted 20 August 2009.

Background/Purpose

Oral squamous cell carcinoma (OSCC) is an aggressive tumor and its occurrence in Taiwan is closely related to chronic smoking, alcohol consumption, and especially to betel quid chewing. It became the fourth most common malignant tumor of Taiwanese men in 2006. Unfortunately, there are few biomarkers for diagnosis and treatment of this disease.

Methods

To find potential markers, two domestic cell lines (OC2 and OCSL) derived from different grades of OSCC were established and their proteins were compared by global proteomic analysis. The expression differences of GRP78 protein in these two cell lines and clinical samples from OSCC patients were verified.

Results

Of the 11 candidate proteins expressed differentially in both cell lines, six [heat shock protein 90 kDa beta member 1 (94 kDa glucose-regulated protein; GRP94), protein disulfide-isomerase precursor, vimentin, tubulin beta-2C chain, 78 kDa glucose-regulated protein precursor (GRP78), and annexin A2] were increased in OC2 cells (low-grade OSCC), and five (heat shock protein 90-beta, annexin A1, stress-induced phosphoprotein 1, elongation factor-2, and integrin alpha-3 precursor) were increased in OCSL cells (high-grade OSCC). Some of these proteins have been previously associated with malignant tumors, but no previous association of GRP78 with OSCC has been reported. GRP78 protein expression in these two OSCC cell lines was confirmed by Western blotting. Immunohistochemical staining of clinical samples from OSCC patients revealed that decreased GRP78 protein expression was significantly correlated with advance tumor stage (p < 0.001) and neck lymph node metastasis (p = 0.001).