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免疫检查点分子含V结构域免疫球蛋白4是多发性骨髓瘤的独立预后因素。

The immune checkpoint molecule V-set Ig domain-containing 4 is an independent prognostic factor for multiple myeloma.

作者信息

Roh Jin, Jeon Youkyoung, Lee A-Neum, Lee Sang Min, Kim YeonMee, Sung Chang Ohk, Park Chan-Jeoung, Hong Jung Yong, Yoon Dok Hyun, Suh Cheolwon, Huh Jooryung, Choi Inhak, Park Chan-Sik

机构信息

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

Department of Microbiology and Immunology, Advanced Research Center for Multiple Myeloma, Inje University College of Medicine, Busan, Korea.

出版信息

Oncotarget. 2017 Jul 22;8(35):58122-58132. doi: 10.18632/oncotarget.19468. eCollection 2017 Aug 29.

Abstract

Multiple myeloma (MM) remains as an incurable disease, despite recent substantial improvements in treatment. Therefore, development of novel biomarkers for risk stratification and new therapeutic targets are imperative. One of the emerging treatments for MM is the immune checkpoint blockades. V-set Ig domain-containing 4 (VSIG4) is a lately studied B7-related immune checkpoint modulator. We assessed the VSIG4 expression in patients with MM and its prognostic impact. We analyzed 81 bone marrow and 66 extramedullary biopsy samples of MM patients using immunohistochemistry. VSIG4 mRNA expression data from the Multiple Myeloma Genomics Portal (MMGP) were analyzed to validate our results. The overall survival (OS) of the high VSIG4 expression group was significantly poorer than that of the low VSIG4 expression group ( = 0.046). VSIG4 expression was remained statistically significant after adjustment for revised international staging system (rISS) and Mayo stratification algorithm (mSMART) risk classification, respectively ( = 0.019 and 0.017). Corroborating results were also observed on analyses of VSIG4 expression in patients with extramedullary MM and external data from the MMGP. Our results suggest that VSIG4 expression in MM is an independent indicator of poor prognosis, implying a possible therapeutic target for immunotherapy for MM.

摘要

尽管近期治疗有了显著改善,但多发性骨髓瘤(MM)仍然是一种无法治愈的疾病。因此,开发用于风险分层的新型生物标志物和新的治疗靶点势在必行。MM的新兴治疗方法之一是免疫检查点阻断。含V-set Ig结构域4(VSIG4)是最近研究的一种B7相关免疫检查点调节剂。我们评估了MM患者中VSIG4的表达及其预后影响。我们使用免疫组织化学分析了81例MM患者的骨髓样本和66例髓外活检样本。分析了来自多发性骨髓瘤基因组学门户网站(MMGP)的VSIG4 mRNA表达数据以验证我们的结果。高VSIG4表达组的总生存期(OS)明显低于低VSIG4表达组(P = 0.046)。分别在校正修订的国际分期系统(rISS)和梅奥分层算法(mSMART)风险分类后,VSIG4表达仍具有统计学意义(P = 0.019和0.017)。在对髓外MM患者的VSIG4表达分析和来自MMGP的外部数据中也观察到了相互印证的结果。我们的结果表明,MM中VSIG4表达是预后不良的独立指标,这意味着它可能是MM免疫治疗的一个潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a721/5601638/5990fcee7b4c/oncotarget-08-58122-g001.jpg

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