A novel function for vimentin: the potential biomarker for predicting melanoma hematogenous metastasis
A novel function for vimentin: the potential biomarker for predicting melanoma hematogenous metastasis
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波形蛋白的新功能：预测黑色素瘤血行转移的潜在生物标志物
DOI：
10.1186/1756-9966-29-109
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发表时间：
2010-08-11
影响因子：
11.3
通讯作者：
Zhao, Xiulan
中科院分区：
文献类型：
--
作者：
Li, Man;Zhang, Baogang;Zhao, Xiulan
背景恶性黑色素瘤（MM）的发病率比世界上大多数肿瘤的发病率都要快，黑色素瘤转移仍然是最棘手的问题。方法采用B16 F10皮下移植法建立8只小鼠自发性肺转移模型。采用双向差异凝胶电泳（2D-DIGE）结合基质辅助激光解吸电离飞行时间质谱（MALDI-TOF/MS）技术，检测亲本B16 F10（B16组）和相应肺转移瘤（B16 M组）两种皮下移植瘤组织的差异蛋白质谱。采用Western blotting方法对结果进行验证，并进一步检测个体差异蛋白的临床意义B16 M组中高表达的蛋白质包括细胞骨架蛋白和结构蛋白（波形蛋白、γ-肌动蛋白、β-肌动蛋白、层粘连蛋白结合蛋白）、蛋白质伴侣家族（重链结合蛋白、Bip）、免疫蛋白酶体组装（蛋白酶体激活剂REG α）以及参与糖酵解活性（PGK 1、烯醇化酶、TPI、人骨骼肌GAPDH）和蛋白质转运（肌红蛋白）的其他蛋白质。Western blotting结果显示，与B16组相比，B16 M组Vimentin表达明显上调。免疫组化结果显示，Vimentin在有血行转移的原发性黑色素瘤组织中高表达（P< 0.05），与淋巴结转移无关（P> 0.05）。TNM分期是恶性黑色素瘤患者预后不良的独立指标（P= 0.004）。结论Vimentin在恶性黑色素瘤组织中的异常表达可能有助于提高对恶性黑色素瘤患者血行转移高危因素的认识。这可能是黑色素瘤转移的一个新指标。总之，波形蛋白不仅是黑色素瘤临床诊断的标志物，而且是黑色素瘤血行转移的预测因子。
BackgroundThe incidence of malignant melanoma (MM) was occurring at a faster rate than for most neoplasm worldwide, and melanoma metastasis is still the most formidable problem. So it is necessarily to find some biomarkers associated with melanoma metastasis.MethodsIn our study, 8 spontaneous lung metastatic mice models were created by B16F10 subcutaneously transplantation. The differential protein profiles of two kinds of subcutaneous transplanted tumor tissues, which was parental B16F10 (B16 group) and corresponding lung metastases (B16M group) were detected by two-dimensional differential in-gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Western blotting was used to validate the results, and the clinical significance of individual protein was detected furtherly in a set of human samples.ResultIn this study, thirty proteins were found to be differentially expressed (ratio > 2 or < -2,P< 0.01) and thirteen of them were identified by MS. Highly expressed proteins in B16M group included cytoskeleton/structure proteins (vimentin, gamma-actin, β-actin, laminin binding protein), the chaperone family of proteins (heavy-chain binding protein, Bip), immunoproteasome assembly (proteasome activator REG alpha) and others involved in glycolysis activity (PGK1, enolase, TPI, human skeletal muscle GAPDH) and protein transport (myoglobin). Vimentin was significantly up-regulated in B16M group compared with B16 group which was validated by western blotting. Immunohistochemistry was performed in a set of clinical samples, the results showed that over-expression of vimentin was frequently observed in primary melanoma patients with hematogenous metastasis (P< 0.05), not associated with lymph node metastasis (P> 0.05). The presence of TNM stage was a independent indicator of poor prognosis for melanoma patients (P= 0.004).ConclusionThe aberrant immunohistochemical expression of vimentin in primary melanoma tissues may help to call attention for patients with high risk of hematogenous metastasis. That might be as a novel metastatic indicator for melanoma. In a word, vimentin is not only the dignostic marker but also the hematogenous metastasis predictor for melanomas clinically.