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多发性骨髓瘤中的 Transgelin-2:肾功能障碍的新标志物?

Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?

机构信息

Chair and Department of Nephrology, Jagiellonian University Medical College, 30-688 Kraków, Poland.

Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland.

出版信息

Molecules. 2021 Dec 23;27(1):79. doi: 10.3390/molecules27010079.

DOI:10.3390/molecules27010079
PMID:35011306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8746652/
Abstract

Transgelin is a 22-kDa protein involved in cytoskeletal organization and expressed in smooth muscle tissue. According to animal studies, it is a potential mediator of kidney injury and fibrosis, and moreover, its role in tumorigenesis is emerging in a variety of cancers. The study included 126 ambulatory patients with multiple myeloma (MM). Serum transgelin-2 concentrations were measured by enzyme-linked immunoassay. We evaluated associations between baseline transgelin and kidney function (serum creatinine, estimated glomerular filtration rate-eGFR, urinary markers of tubular injury: cystatin-C, neutrophil gelatinase associated lipocalin-NGAL monomer, cell cycle arrest biomarkers IGFBP-7 and TIMP-2) and markers of MM burden. Baseline serum transgelin was also evaluated as a predictor of kidney function after a follow-up of 27 months from the start of the study. Significant correlations were detected between serum transgelin-2 and serum creatinine (R = 0.29; = 0.001) and eGFR (R = -0.25; = 0.007). Transgelin significantly correlated with serum free light chains lambda (R = 0.18; = 0.047) and serum periostin (R = -0.22; = 0.013), after exclusion of smoldering MM patients. Patients with decreasing eGFR had higher transgelin levels (median 106.6 versus 83.9 ng/mL), although the difference was marginally significant ( = 0.05). However, baseline transgelin positively correlated with serum creatinine after the follow-up period (R = 0.37; < 0.001) and negatively correlated with eGFR after the follow-up period (R = -0.33; < 0.001). Moreover, higher baseline serum transgelin (beta = -0.11 ± 0.05; = 0.032) significantly predicted lower eGFR values after the follow-up period, irrespective of baseline eGFR and follow-up duration. Our study shows for the first time that elevated serum transgelin is negatively associated with glomerular filtration in MM and predicts a decline in renal function over long-term follow-up.

摘要

转胶蛋白是一种 22kDa 的蛋白质,参与细胞骨架组织,并在平滑肌组织中表达。根据动物研究,它是肾脏损伤和纤维化的潜在介质,而且,它在多种癌症中的肿瘤发生作用正在出现。该研究纳入了 126 例门诊多发性骨髓瘤(MM)患者。通过酶联免疫吸附试验测定血清转胶蛋白-2 浓度。我们评估了基线转胶蛋白与肾功能(血清肌酐、估计肾小球滤过率-eGFR、肾小管损伤的尿标志物:胱抑素-C、中性粒细胞明胶酶相关脂质运载蛋白-NGAL 单体、细胞周期阻滞生物标志物 IGFBP-7 和 TIMP-2)和 MM 负担标志物之间的相关性。还评估了基线血清转胶蛋白作为研究开始后 27 个月随访期间肾功能的预测因子。检测到血清转胶蛋白-2 与血清肌酐(R = 0.29; = 0.001)和 eGFR(R = -0.25; = 0.007)之间存在显著相关性。排除冒烟型 MM 患者后,转胶蛋白与血清游离轻链 lambda(R = 0.18; = 0.047)和血清骨膜蛋白(R = -0.22; = 0.013)显著相关。eGFR 下降的患者转胶蛋白水平较高(中位数 106.6 与 83.9ng/mL),尽管差异具有边缘显著性( = 0.05)。然而,基线转胶蛋白在随访期间与血清肌酐呈正相关(R = 0.37; <0.001),在随访期间与 eGFR 呈负相关(R = -0.33; <0.001)。此外,较高的基线血清转胶蛋白(β=-0.11 ± 0.05; = 0.032)独立于基线 eGFR 和随访时间,显著预测了随访后的 eGFR 值降低。我们的研究首次表明,升高的血清转胶蛋白与 MM 中的肾小球滤过率呈负相关,并预测了长期随访中肾功能的下降。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f4/8746652/3d3401759003/molecules-27-00079-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f4/8746652/4ea5f26e28cc/molecules-27-00079-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f4/8746652/3d3401759003/molecules-27-00079-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f4/8746652/4ea5f26e28cc/molecules-27-00079-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29f4/8746652/3d3401759003/molecules-27-00079-g002.jpg

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