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      Prognostic value of CD44 expression in renal cell carcinoma: a systematic review and meta-analysis

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          Abstract

          CD44 is a marker of cancer stem-like cells in renal cell carcinoma (RCC). However, the prognostic value of CD44 in RCC remains controversial. This study evaluated the correlation of CD44 expression with the clinicopathological features of RCC through a meta-analysis. We systematically searched PubMed, ISI Web of Science and Embase for relevant studies until February 2015. We collected and analysed data on clinical stage, Fuhrman grade, microvascular invasion, recurrence, five-year overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Twenty studies involving 1672 patients satisfied the inclusion criteria. Results showed that high CD44 expression in RCC was a poor prognostic marker for five-year OS (RR = 0.69, 95% CI 0.60–0.78) in a fixed-effects model and for five-year DSS (RR = 0.46, 95% CI 0.27–0.80) and five-year DFS (RR = 0.63, 95% CI 0.43–0.93) in a random-effects model. CD44 expression also correlated with Furhman grade (RR = 0.61, 95% CI 0.48–0.77), tumour recurrence (RR = 7.42, 95% CI 3.74–14.70) and MVI (Microvascular invasion) (RR = 3.63, 95% CI 1.97–6.71). This meta-analysis suggests that CD44 is a prognostic marker in RCC. High CD44 expression correlates with high Fuhrman grade, recurrence, MVI and poor prognosis.

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          Most cited references27

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          Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review.

          Renal cell carcinoma (RCC), the most common form of kidney cancer, initially has an asymptomatic clinical course; 25-30% of patients present with metastatic disease at time of diagnosis. Worldwide incidence and mortality rates are rising at a rate of approximately 2-3% per decade. Metastatic RCC (mRCC) is one of the most treatment-resistant malignancies; outcomes are generally poor and median survival after diagnosis is less than one year. Surgery and chemotherapy have limited or no effect, leaving mRCC patients underserved in the realm of cancer treatment. As the world's population ages and the prevalence of risk factors (obesity, hypertension) increases, the burden of mRCC is predicted to increase significantly. With a shift in treatment of mRCC to novel therapies, such as molecularly targeted therapies (MTTs) (e.g., sorafenib and sunitinib), clinicians, payers, and other healthcare decision-makers must re-evaluate the optimal role for new treatments. Timely understanding of the burden of mRCC on individuals and society clearly is needed at this juncture. Using a comprehensive literature review, we assessed the epidemiologic, economic, and health-related quality of life (HRQOL) burdens of mRCC. The annual incidence of mRCC in major European countries, the US, and Japan ranges from 1500 to 8600 cases. However, prevalence data were lacking. The estimated economic burden of mRCC is large; $107-$556 million (2006 USD) in the US and $446 million-$1.6 billion (2006 USD) collectively in select countries worldwide. MTTs have potential to reduce the burden of mRCC and provide substantial value beyond their clinical effectiveness.
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            Hyaluronan-mediated CD44 activation of RhoGTPase signaling and cytoskeleton function promotes tumor progression.

            Hyaluronan (HA), a major component of the extracellular matrix (ECM), is enriched in many types of tumors. In cancer patients HA concentrations are usually higher in malignant tumors than in corresponding benign or normal tissues, and in some tumor types the level of HA is predictive of malignancy. HA is often bound to CD44 isoforms which are ubiquitous, abundant, and functionally important cell surface receptors. This article reviews the current evidence for HA/CD44-mediated activation of the ankyrin-based cytoskeleton and RhoGTPase signaling during tumor progression. A special focus is placed on the role of HA-mediated CD44 interaction with unique downstream effectors (e.g., the cytoskeletal protein, ankyrin and/or various GTPases (e.g., RhoA, Rac1 and Cdc42)) in coordinating intracellular signaling pathways (e.g., Ca(2+) mobilization, Rho signaling, PI3 kinase-AKT activation, NHE1-mediated cellular acidification, transcriptional upregulation and cytoskeletal function) and generating the concomitant onset of tumor cell activities (e.g., tumor cell adhesion, growth, survival, migration and invasion) and tumor progression. I believe this information will provide valuable new insights into poorly understood aspects of solid tumor malignancy. Furthermore, the new knowledge concerning HA/CD44-mediated oncogenic signaling events will have potentially important clinical utility, and could establish CD44 and its associated signaling molecules as important tumor markers for the early detection and evaluation of oncogenic potential. It could also serve as ground work for the future development of new drug targets to inhibit HA/CD44-mediated tumor metastasis and cancer progression.
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              Prognostic significance of the cancer stem cell markers CD133, CD44, and CD166 in colorectal cancer.

              CD133, CD44, and CD166 are cell surface markers that have recently been associated with colorectal cancer stem cells. As which of these markers has the greatest impact on patient prognosis is currently unknown, we compared their expression and prognostic significance in 110 colorectal adenocarcinomas. We demonstrate that expression of CD133 correlates with that of CD166, while both do not correlate with CD44. We show that CD133 is the best sole marker to predict low patient survival, while the combined analysis of all three markers may be superior in identification of low-, intermediate-, and high-risk cases of colorectal cancer.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                19 August 2015
                2015
                : 5
                : 13157
                Affiliations
                [1 ]Department of Urology, State Key Laboratory of Kidney Disease, PLA Medical School, Chinese People’s Liberation Army General Hospital , Beijing, China
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                srep13157
                10.1038/srep13157
                4541415
                26287771
                0e280891-7e2d-4c36-a931-17cd7851eb9c
                Copyright © 2015, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 07 April 2015
                : 03 July 2015
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