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      High expression of TRPM8 predicts poor prognosis in patients with osteosarcoma

      research-article
      ,
      Oncology Letters
      D.A. Spandidos
      TRPM8, osteosarcoma, prognosis, overall survival, disease-free survival

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          Abstract

          The transient receptor potential melastatin member 8 (TRPM8) is a newly characterized oncoprotein involved in various malignant tumors. However, its expression pattern and biological function in osteosarcoma remain unclear. The present study aimed to explore the expression and prognostic significance of TRPM8 in osteosarcoma (OS). The results revealed that the expression of TRPM8 mRNA and protein in OS tissue was significantly higher than that in paired normal bone tissue (P<0.05). Additionally, the level of TRPM8 mRNA and protein in patients with a higher clinical stage and with distant metastasis was markedly higher than in those with a lower clinical stage and no metastasis (P<0.05). Furthermore, a high TRPM8 level was closely associated with clinical stage and distant metastasis (P=0.007 and 0.030), but not associated with the patient age (P=0.481), gender (P=0.905), tumor size (P=0.429), histological subtype (P=0.207) or anatomical location (P=0.369). In addition, OS patients with high TRPM8 expression had significantly shorter overall survival (P=0.008) and disease-free survival times (P=0.008) when compared with patients with low expression of TRPM8. In Cox multivariate analysis, TRPM8 overexpression was identified to be an independent and significant prognostic factor for overall survival (P=0.040), but not for disease-free survival (P=0.051). Collectively, the present data suggest that TRPM8 may play a crucial role in the development and progression of OS, and thus may be considered as a novel molecular target for therapy in patients with OS.

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          Most cited references25

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          Prognostic and predictive factors in early-stage breast cancer.

          Breast cancer is the most common malignancy among American women. Due to increased screening, the majority of patients present with early-stage breast cancer. The Oxford Overview Analysis demonstrates that adjuvant hormonal therapy and polychemotherapy reduce the risk of recurrence and death from breast cancer. Adjuvant systemic therapy, however, has associated risks and it would be useful to be able to optimally select patients most likely to benefit. The purpose of adjuvant systemic therapy is to eradicate distant micrometastatic deposits. It is essential therefore to be able to estimate an individual patient's risk of harboring clinically silent micrometastatic disease using established prognostic factors. It is also beneficial to be able to select the optimal adjuvant therapy for an individual patient based on established predictive factors. It is standard practice to administer systemic therapy to all patients with lymph node-positive disease. However, there are clearly differences among node-positive women that may warrant a more aggressive therapeutic approach. Furthermore, there are many node-negative women who would also benefit from adjuvant systemic therapy. Prognostic factors therefore must be differentiated from predictive factors. A prognostic factor is any measurement available at the time of surgery that correlates with disease-free or overall survival in the absence of systemic adjuvant therapy and, as a result, is able to correlate with the natural history of the disease. In contrast, a predictive factor is any measurement associated with response to a given therapy. Some factors, such as hormone receptors and HER2/neu overexpression, are both prognostic and predictive.
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            New targets and approaches in osteosarcoma.

            Osteosarcoma is the most common primary tumor of bone. Approximately 2/3 of patients who present with localized osteosarcoma can be expected to be cured of their disease with surgery and routine chemotherapy. Only 1/3 of patients with metastases detectable at presentation will be cured. These survival trends have stagnated over the past 20 years using conventional chemotherapy. New agents need to be rationally investigated to strive for improvement in the survival of patients diagnosed with osteosarcoma. This manuscript will review the rationale for conventional chemotherapy used in the treatment of osteosarcoma, as well as agents in varying stages of development that may have promise for treatment in the future. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins.

              We have identified and cloned a novel gene, trp-p8, by screening a prostate-specific subtracted cDNA library. The 5694-bp cDNA has a 3312-bp open reading frame, which codes for a 1104 amino acid putative protein with seven transmembrane domains. The predicted protein revealed significant homology with the transient receptor potential (trp) family of Ca(2+) channel proteins. Northern blot analysis indicated that trp-p8 expression within normal human tissues is mostly restricted to prostate epithelial cells. In situ hybridization analysis showed that trp-p8 mRNA expression was at moderate levels in normal prostate tissue and appears to be elevated in prostate cancer. Notably, trp-p8 mRNA was also expressed in a number of nonprostatic primary tumors of breast, colon, lung, and skin origin, whereas transcripts encoding trp-p8 were hardly detected or not detected in the corresponding normal human tissues.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                August 2016
                22 June 2016
                22 June 2016
                : 12
                : 2
                : 1373-1379
                Affiliations
                Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
                Author notes
                Correspondence to: Mr. Huimian Xu, Department of Surgical Oncology, The First Hospital of China Medical University, 155 Nanjingbei Street, Shenyang, Liaoning 110001, P.R. China, E-mail: xuhuimian1956@ 123456163.com
                Article
                OL-0-0-4764
                10.3892/ol.2016.4764
                4950156
                27446440
                23179d4f-51bc-4165-860f-d19e526b886d
                Copyright: © Zhao et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 18 January 2015
                : 24 February 2016
                Categories
                Articles

                Oncology & Radiotherapy
                trpm8,osteosarcoma,prognosis,overall survival,disease-free survival
                Oncology & Radiotherapy
                trpm8, osteosarcoma, prognosis, overall survival, disease-free survival

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