Table_1_Prognostic value of dysadherin in cancer: A systematic review and meta-analysis.xlsx

Cancer is a leading cause of death worldwide and novel prognostic factors are reported with increasing numbers. Systematic reviews and meta-analyses on cumulative research data are crucial in estimating the true prognostic value of proposed factors. Dysadherin (FXYD Domain Containing Ion Transport Regulator 5; FXYD5) is a cell membrane glycoprotein that modulates Na+, K+-ATPase activity and cell-cell adhesion. It is abundantly expressed in a variety of cancer cells, but only in a limited number of normal cells and its levels are increased in many different tumor types. The expression or level of dysadherin has been suggested as an independent predictor for metastasis and poor prognosis by number of studies, yet we lack a definitive answer. In this study, we systematically evaluated the prognostic value of dysadherin in cancer and summarized the current knowledge on the subject. PubMed, Scopus, Web of Science and relevant clinical trial and preprint databases were searched for relevant publications and PRISMA and REMARK guidelines were applied in the process. After a careful review, a total of 23 original research articles were included. In each study, dysadherin was pointed as a marker for poor prognosis. Meta-analyses revealed 3- and 1.5-fold increases in the risk of death (fixed effects HR 3.08, 95% CI 1.88-5.06, RR 1.47, 95% CI 1.06-2.05 on overall survival, respectively) for patients with high (>50%) tumoral FXYD5 level. In many studies, a connection between dysadherin expression or level and metastatic behavior of the cancer as well as inverse correlation with E-cadherin level were reported. Thus, we conclude that dysadherin might be a useful prognostic biomarker in the assessment of disease survival of patients with solid tumors.

癌症是全球主要的死亡原因，而新的预后因素正日益增多。对累积研究数据的系统综述和荟萃分析对于评估所提出因素的真正预后价值至关重要。Dysadherin（FXYD结构域含离子转运调节因子5；FXYD5）是一种细胞膜糖蛋白，它调节Na+、K+-ATPase的活性以及细胞间的粘附。Dysadherin在多种癌细胞中表达丰富，但在正常细胞中仅存在于有限的数目，并且其在多种肿瘤类型中的水平均有所升高。众多研究表明，Dysadherin的表达或水平可能作为独立预测因子，预测转移和不良预后，然而，我们仍缺乏明确的结论。在本研究中，我们系统地评估了Dysadherin在癌症中的预后价值，并总结了关于该主题的现有知识。通过PubMed、Scopus、Web of Science以及相关的临床试验和预印本数据库，我们检索了相关出版物，并在整个过程中遵循了PRISMA和REMARK指南。经过仔细审查，共纳入了23篇原始研究文章。在每一项研究中，Dysadherin都被指认为不良预后的标志物。荟萃分析显示，对于肿瘤FXYD5水平高（>50%）的患者，死亡风险增加了3倍和1.5倍（固定效应HR 3.08，95% CI 1.88-5.06，RR 1.47，95% CI 1.06-2.05，分别针对总生存期）。在许多研究中，Dysadherin的表达或水平与癌症的转移行为之间存在关联，同时与E-钙粘蛋白水平呈负相关。因此，我们得出结论，Dysadherin可能成为评估实体瘤患者疾病生存的有用预后生物标志物。