Elevated serum concentration of hepatocyte growth factor in patients with multiple myeloma: Correlation with markers of disease activity
Elevated serum concentration of hepatocyte growth factor in patients with multiple myeloma: Correlation with markers of disease activity
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DOI：
10.1002/ajh.10304
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发表时间：
2003-04-01
影响因子：
12.8
通讯作者：
Kyriakou, DS
中科院分区：
文献类型：
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作者：
Alexandrakis, MG;Passam, FH;Kyriakou, DS
肝细胞生长因子（HGF）已被证明参与血管生成，上皮细胞增殖和破骨细胞活化。HGF及其受体在骨髓瘤细胞系中表达，并可能参与多发性骨髓瘤（MM）骨破坏的发病机制。本研究的目的是检测未经治疗的MM患者血清HGF水平及其与骨转换指数和疾病活动标志物的相关性。纳入47例新诊断的MM患者和25例对照：12例患者为I期，13例为II期，22例为III期（Durie-Salmon分类）。根据X线检查结果，骨病变评分为0 - 3分。测定血清骨钙素（OC）、白细胞介素-6（IL-6）、TNF-α、β（2）-微球蛋白（β（2）M）、CRIP、钙和24小时尿胶原分解N-端肽交联（NTx）。与II期和I期相比，III期的HGF水平显著更高（中位数：分别为1，990.4 vs. 1，743.8和1，432.4 pg/mL，P < 0.05）。NTx、IL-6、TNF-α、CRIP、β 2-M和钙离子浓度随临床分期的进展而显著升高（P < 0.01）。OC在I期高于11期和III期（P < 0.01）。患者的所有参数均显著高于对照组。HGF与IL-6和TNF-α的相关性较强，与β 2 M、CRP、NTx和OC的相关性较弱。我们得出结论，血清HGF水平增加，在MM疾病的晚期和扩展的骨病变。HGF与IL-6和TNF-α相关，它们是MM中参与破骨细胞刺激的细胞因子。然而，本研究中未显示HGF与骨转换标志物的独立关联，因此其在MM骨病中的作用需要进一步阐明。(C)2003 Wiley-Liss，Inc.
Hepatocyte growth factor (HGF) has been shown to be involved in angiogenesis, epithelial cell proliferation, and osteoclast activation. HGF and its receptor are expressed on myeloma cell lines and could be involved in the pathogenesis of bone destruction in multiple myeloma (MM). The aim of this study was to examine serum levels of HGF in untreated MM patients and its correlation with bone turnover indices and markers of disease activity. Forty-seven newly diagnosed MM patients and 25 controls were included: 12 patients were of stage I, 13 of stage II, and 22 of stage III (Durie-Salmon classification). Bone lesions were scored from 0 to 3, according to X-ray findings. Serum osteocalcin (OC), interleukin-6 (IL-6), TNF-alpha, beta(2)-microglobulin (beta(2)M), CRIP, calcium, and 24-hr urine N-telopeptide cross-links of collagen breakdown (NTx) were determined. HGF levels were significantly higher at stage III compared to stages II and I (medians: 1,990.4 vs. 1,743.8 and 1,432.4 pg/mL, respectively, P < 0.05). Similarly, NTx, IL-6, TNF-alpha, CRIP, beta(2)M, and calcium increased significantly with advancing stage (P < 0.01). OC was higher at stage I in comparison to stages 11 and III (P < 0.01). All parameters were significantly higher in patients than controls. HGF showed a strong correlation with IL-6 and TNF-alpha and less with beta(2)M, CRP, NTx, and OC. We conclude that serum HGF levels are increased in advanced stages of MM disease and extended bone lesions. HGF correlates with IL-6 and TNF-alpha, which are cytokines involved in osteoclast stimulation in MM. However, an independent association of HGF with bone turnover markers was not shown in this study, thus its role in MM bone disease needs to be further clarified. (C) 2003 Wiley-Liss, Inc.