Underexpression of α-1-microglobulin/bikunin precursor predicts a poor prognosis in oral squamous cell carcinoma

Sekikawa,Shoichi; Onda,Takeshi; Miura,Nami; Nomura,Takeshi; Takano,Nobuo; Shibahara,Takahiko; Honda,Kazufumi

doi:10.3892/ijo.2018.4581

Underexpression of α-1-microglobulin/bikunin precursor predicts a poor prognosis in oral squamous cell carcinoma

Authors:
- Shoichi Sekikawa
- Takeshi Onda
- Nami Miura
- Takeshi Nomura
- Nobuo Takano
- Takahiko Shibahara
- Kazufumi Honda
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Affiliations: Department of Oral and Maxillofacial Surgery, Tokyo Dental College, Chiba 261-8502, Japan, Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo 104-0045, Japan, Department of Oral Medicine, Oral and Maxillofacial Surgery, Tokyo Dental College, Chiba 272-8513, Japan, Oral Cancer Center, Tokyo Dental College, Chiba 272-8513, Japan
Published online on: October 1, 2018 https://doi.org/10.3892/ijo.2018.4581
Pages: 2605-2614

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Abstract

In the present study, in order to identify novel diagnostic biomarkers for the malignant behavior of oral squamous cell carcinoma (OSCC), we determined the proteomic profiles of several OSCC cell lines and keratinocytes by two-dimensional fluorescence difference gel electrophoresis and liquid chromatography tandem mass spectrometry. The protein expression level of α-1-microglobulin/bikunin precursor (AMBP) was found to be significantly lower in the OSCC cell lines than in the keratinocytes, and a significant decrease in AMBP mRNA expression was confirmed in the OSCC cell lines by RT-qPCR. To investigate the biological function of AMBP in OSCC, the cells were transiently transfected with an AMBP overexpression vector; the AMBP-overexpressing cells exhibited a significantly decreased invasion and migration in comparison to the mock-transfected control cells, although no significant changes in cell proliferation were observed. Immunohistochemistry revealed that the underexpression of AMBP was significantly associated with a high metastatic potential to cervical lymph nodes and a poor overall survival. Thus, the expression of AMBP is an independent predictive factor of cervical lymph node metastasis and a prognostic factor of overall survival, and it is involved in both cell invasion and metastasis in cervical lymph nodes in OSCC.

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