Oncotarget

Research Papers:

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

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

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Oncotarget. 2017; 8:58122-58132. https://doi.org/10.18632/oncotarget.19468

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Abstract

Jin Roh1, Youkyoung Jeon6, A-Neum Lee4,5, Sang Min Lee7, YeonMee Kim8, Chang Ohk Sung1, Chan-Jeoung Park3, Jung Yong Hong2, Dok Hyun Yoon2, Cheolwon Suh2, Jooryung Huh1, Inhak Choi6,* and Chan-Sik Park1,4,5,*

1Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

2Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

3Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

4Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

5Cell Dysfunction Research Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

6Department of Microbiology and Immunology, Advanced Research Center for Multiple Myeloma, Inje University College of Medicine, Busan, Korea

7Department of Hematology/Oncology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea

8Department of Pathology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea

*These authors have contributed equally to this work

Correspondence to:

Chan-Sik Park, email: [email protected]

Inhak Choi, email: [email protected]

Keywords: multiple myeloma, immune checkpoint, VSIG4, immunohistochemistry, prognosis

Received: November 14, 2016    Accepted: June 20, 2017    Published: July 22, 2017

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 (p = 0.046). VSIG4 expression was remained statistically significant after adjustment for revised international staging system (rISS) and Mayo stratification algorithm (mSMART) risk classification, respectively (p = 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.


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