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      Prognostic role of podocalyxin-like protein expression in various cancers: A systematic review and meta-analysis

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          Abstract

          Several studies were conducted to explore the prognostic significance of podocalyxin-like protein (PODXL) expression in various cancers, with contradictory. This study aims to summarize the prognostic significance of PODXL expression in cancers. PubMed, the Cochrane Library and Embase were completely retrieved. The prospective or retrospective studies focusing on the prognostic role of PODXL expression in cancers were eligible. The endpoints were overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS).12 studies involving a total of 5,309 patients were identified. The results indicated that high PODXL expression was significantly associated with worse OS when compared to the low PODXL expression (HR=1.76, 95%CI=1.53-2.04, p<0.00001; I 2=41%, p=0.08). And similar results were detected in the subgroup analysis of analysis model, ethnicity, sample size, tumor type and antibody type. And the results also showed that high PODXL expression was obviously related to shorter DSS (HR=2.47, 95%CI=1.53-3.99, p=0.0002; I 2=66%, p=0.03) and DFS (HR=2.12, 95%CI=1.58-2.85, p<0.00001; I 2=19%, p=0.29). In conclusion, it was revealed that high PODXL expression is an unfavorable predictor of OS, DSS and DFS in patients with cancers, and high PODXL expression is a promising prognostic biomarker for cancers, especially for patients in European.

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          Most cited references23

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          Identification and characterization of podocalyxin--the major sialoprotein of the renal glomerular epithelial cell

          The glomerular epithelial polyanion is a specialized cell surface component found on renal glomerular epithelial cells (podocytes) that is rich in sialoprotein(s), as detected by staining with cationic dyes (colloidal iron, alcian blue) and wheat germ agglutinin (WGA). We have isolated rat glomeruli and analyzed their protein composition by SDS PAGE in 5-10% gradient gels. When the gels were stained with alcian blue or "Stains All," a single band with an apparent Mr of 140,000 was detected that also stained very prominently with silver, but not with Coomassie Blue. This band predominated in fluorograms of gels of isolated glomeruli that had been labeled in their sialic acid residues by periodate-[3H]borohydride. In lectin overlays, the 140-kilodalton (kd) band was virtually the only one that bound [125I]wheat germ agglutinin, and this binding could be prevented by predigestion with neuraminidase. [125I]Peanut lectin bound exclusively to the 140-kd band after neuraminidase treatment. An antibody was prepared that specifically recognizes only the 140-kd band by immunoprecipitation and immuneoverlay. By immunoperoxidase and immunogold techniques, it was localized to the surface coat of the glomerular epithelium and, less extensively, to that of endothelial cells. When analyzed (after electroelution from preparative SDS gels), the 140-kd band was found to contain approximately 20% hexose and approximately 4.5% sialic acid. These findings indicate that the 140-kd protein is the major sialoprotein of the glomerulus, and it is the only component of glomerular lysates with an affinity for cationic dyes and lectins identical to that defined histochemically for the epithelial polyanion in situ. Since this molecule is a major component of the cell coat or glycocalyx of the podocytes, we have called it "podocalyxin."
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            The role of podocalyxin in health and disease.

            Podocalyxin, a sialomucin most closely related to CD34 and endoglycan, is expressed by kidney podocytes, hematopoietic progenitors, vascular endothelia, and a subset of neurons; aberrant expression has recently been implicated in a range of cancers. Through interactions with several intracellular proteins and at least one extracellular ligand, podocalyxin regulates both adhesion and cell morphology. In the developing kidney, podocalyxin plays an essential role in the formation and maintenance of podocyte foot processes, and its absence results in perinatal lethality. Podocalyxin expression in the hematopoietic system correlates with cell migration and the seeding of new hematopoietic tissues. In addition, it is abnormally expressed in subsets of breast, prostate, liver, pancreatic, and kidney cancer as well as leukemia. Strikingly, it is often associated with the most aggressive cases, and it is likely involved in metastasis. Thus, a thorough investigation of the normal activities of podocalyxin may facilitate the development of new cancer treatment strategies.
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              Cancer cells in transit: the vascular interactions of tumor cells.

              Metastasis is a highly regulated, multistep process in which cancerous cells shed from the primary tumor and enter the circulatory system, where they interact extensively with host cells before they lodge and colonize the target organ. The adhesive interactions of circulating tumor cells with platelets, leukocytes, and endothelial cells facilitate their survival and extravasation from the vasculature, thus representing critical kick-off events for the colonization of distant organs. This review presents our current mechanistic knowledge on vascular interactions of tumor cells, and it discusses biochemical and cell and molecular biology techniques used for the identification of novel receptor-ligand pairs mediating these interactions. This review brings together diverse observations about the contributions of key molecular constituents, including selectins, fibrin(ogen), and CD44, in one mechanistic interpretation. Understanding the molecular underpinnings of adhesive interactions between tumor cells and host cells may provide guidelines for developing promising antimetastatic therapies when initiated early in the course of disease progression.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                8 August 2017
                25 December 2016
                : 8
                : 32
                : 52457-52464
                Affiliations
                1 Department of Hepatobiliary Disease, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
                2 School of Medicine, Tongji University, Shanghai, China
                3 Department of General Surgery, 302 Hospital of PLA, Beijing, China
                Author notes
                Correspondence to: Yongzhao Zhao, yongzhao_zhao@ 123456163.com
                Shengzhi Wang, 994233529@ 123456qq.com
                Article
                14199
                10.18632/oncotarget.14199
                5581042
                28881743
                15be6641-319b-4df6-8b27-44fde29ece97
                Copyright: © 2017 Wang et al.

                This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 19 October 2016
                : 20 November 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                prognostic,podocalyxin-like protein,cancer,overall survival
                Oncology & Radiotherapy
                prognostic, podocalyxin-like protein, cancer, overall survival

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