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Prognostic value of glucosylceramide synthase and P-glycoprotein expression in oral cavity cancer

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Abstract

Background

Glucosylceramide synthase (GCS) and P-glycoprotein (P-gp) overexpression are associated with multidrug resistance in several human cancers. This study investigated the prognostic value of GCS and P-gp in oral cavity squamous cell carcinoma (OSCC).

Methods

The association between GCS and P-gp overexpression and clinical outcomes was assessed in 186 human clinical specimens of primary tumors obtained from curative surgery. Immunohistochemistry staining results were scored as high or low for GCS, and positive or negative for P-gp. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to assess the significance of differences in recurrence or survival outcomes between variables.

Results

GCS overexpression was observed in 128 (68.8 %) patients and P-gp overexpression in 43 (23.1 %) patients. High GCS expression was significantly correlated with P-gp immunopositivity (P = 0.005). GCS and P-gp overexpression was significantly correlated with cervical nodal metastasis (P < 0.05). Univariate analyses showed that tumor lymphovascular invasion, positive neck lymph nodes, advanced overall TNM stage, high GCS expression, and P-gp immunopositivity were associated with poor locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) (P < 0.05). Multivariate analyses showed that lymphovascular invasion, nodal positivity, and P-gp overexpression remained independent prognostic variables for LRC, DFS, and OS, and that GCS expression was an independent predictor of LRC and DFS (P < 0.05).

Conclusion

GCS and P-gp expression is associated with poor prognosis, suggesting suitability as novel biomarkers in OSCC.

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Acknowledgments

This study was supported by a grant (no. 2015R1A2A1A15054540) from Basic Science Research Program through the National Research Foundation of Korea (NRF), Ministry of Science, ICT, and Future Planning, and a grant (no. HI15C2920) from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), Ministry of Health and Welfare, Seoul, Republic of Korea (J.L. Roh).

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    Authors and Affiliations

    1. Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea

      Ji Won Kim, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam & Sang Yoon Kim

    2. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

      Yangsoon Park & Kyung-Ja Cho

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    1. Ji Won Kim
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    Correspondence to Jong-Lyel Roh.

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    J. W. Kim and Y. Park equally contributed to this paper.

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    Kim, J.W., Park, Y., Roh, JL. et al. Prognostic value of glucosylceramide synthase and P-glycoprotein expression in oral cavity cancer. Int J Clin Oncol 21, 883–889 (2016). https://doi.org/10.1007/s10147-016-0973-1

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    • DOI: https://doi.org/10.1007/s10147-016-0973-1

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