Lee Byung-Hyun, Kim Ji-Hea, Kang Ka-Won, Lee Se-Ryeon, Park Yong, Sung Hwa-Jung, Kim Byung-Soo
Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Korea.
Department of Biomedical Science, Graduate School of Medicine, Korea University, Seoul 02841, Korea.
Biomedicines. 2022 May 10;10(5):1099. doi: 10.3390/biomedicines10051099.
Poliovirus receptor (PVR, CD155) is upregulated during tumor progression, and PVR expression is associated with poor prognosis in cancer patients; however, prognostic implications for PVR in multiple myeloma (MM) have not been investigated. PVR plays an immunomodulatory role by interacting with CD226, CD96, and TIGIT. TIGIT is a checkpoint inhibitory receptor that can limit adaptive and innate immunity, and it binds to PVR with the highest affinity. We used immunohistochemistry, ELISA, qPCR, and flow cytometry to investigate the role of PVR in MM. PVR was highly expressed in patients with MM, and membrane PVR expression showed a significant correlation with soluble PVR levels. PVR expression was significantly associated with the Revised-International Staging System stage, presence of extramedullary plasmacytoma and bone lesion, percentage of bone marrow plasma cells (BMPCs), and β2-microglobulin levels, suggesting a possible role in advanced stages and metastasis. Furthermore, TIGIT expression was significantly correlated with the percentage of BMPCs. Patients with high PVR expression had significantly shorter overall and progression-free survival, and PVR expression was identified as an independent prognostic factor for poor MM survival. These findings indicate that PVR expression is associated with MM stage and poor prognosis, and is a potential prognostic marker for MM.
脊髓灰质炎病毒受体(PVR,CD155)在肿瘤进展过程中上调,且PVR表达与癌症患者的不良预后相关;然而,PVR在多发性骨髓瘤(MM)中的预后意义尚未得到研究。PVR通过与CD226、CD96和TIGIT相互作用发挥免疫调节作用。TIGIT是一种检查点抑制受体,可限制适应性免疫和先天性免疫,并且它与PVR的结合亲和力最高。我们使用免疫组织化学、酶联免疫吸附测定、定量聚合酶链反应和流式细胞术来研究PVR在MM中的作用。PVR在MM患者中高表达,且膜PVR表达与可溶性PVR水平显著相关。PVR表达与国际分期系统修订版分期、髓外浆细胞瘤和骨病变的存在、骨髓浆细胞(BMPC)百分比以及β2微球蛋白水平显著相关,提示其在疾病晚期和转移中可能发挥作用。此外,TIGIT表达与BMPC百分比显著相关。PVR高表达的患者总生存期和无进展生存期显著缩短,且PVR表达被确定为MM患者不良生存的独立预后因素。这些发现表明,PVR表达与MM分期及不良预后相关,是MM的一个潜在预后标志物。