Department of Clinical and Molecular Medicine, Center for Myeloma Research, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Department of Immunology and Transfusion Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
Eur J Haematol. 2022 Jul;109(1):31-40. doi: 10.1111/ejh.13766. Epub 2022 Mar 20.
Cancer cells can convert proto-oncoproteins into oncoproteins by increasing the expression of genes that are oncogenic when expressed at high levels. Such genes can promote oncogenesis without being mutated. To find overexpressed genes in cancer cells from patients with multiple myeloma, we retrieved mRNA expression data from the CoMMpass database and ranked genes by their expression levels. We grouped the most highly expressed genes based on a set of criteria and we discuss the role a selection of them can play in the disease pathophysiology. The list was highly concordant with a similar list based on mRNA expression data from the PADIMAC study. Many well-known "myeloma genes" such as MCL1, CXCR4, TNFRSF17, SDC1, SLAMF7, PTP4A3, and XBP1 were identified as highly expressed, and we believe that hitherto unrecognized key players in myeloma pathogenesis are also enriched on the list. Highly expressed genes in malignant plasma cells that were absent or expressed at only a low level in healthy plasma cells included IFI6, IFITM1, PTP4A3, SIK1, ALDOA, ATP5MF, ATP5ME, and PSMB4. The ambition of this article is not to validate the role of each gene but to serve as a guide for studies aiming at identifying promising treatment targets.
癌细胞可以通过增加高水平表达时致癌的基因的表达，将原癌蛋白转化为癌蛋白。这些基因可以在没有突变的情况下促进致癌作用。为了从多发性骨髓瘤患者的癌细胞中找到过表达的基因，我们从 CoMMpass 数据库中检索了 mRNA 表达数据，并根据表达水平对基因进行了排序。我们根据一组标准对表达水平最高的基因进行了分组，并讨论了其中一些基因在疾病发病机制中的作用。该列表与基于 PADIMAC 研究的 mRNA 表达数据的类似列表高度一致。许多众所周知的“骨髓瘤基因”，如 MCL1、CXCR4、TNFRSF17、SDC1、SLAMF7、PTP4A3 和 XBP1，被鉴定为高表达，我们认为，骨髓瘤发病机制中以前未被识别的关键因素也在该列表中得到了富集。在恶性浆细胞中高表达而在健康浆细胞中缺失或低表达的基因包括 IFI6、IFITM1、PTP4A3、SIK1、ALDOA、ATP5MF、ATP5ME 和 PSMB4。本文的目的不是验证每个基因的作用，而是为旨在确定有前途的治疗靶点的研究提供指导。
