High levels of DJ-1 protein and isoelectric point 6.3 isoform in sera of breast cancer patients.
High levels of DJ-1 protein and isoelectric point 6.3 isoform in sera of breast cancer patients.
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DOI：
10.1111/cas.12673
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发表时间：
2015-07
期刊：
影响因子：
5.7
通讯作者：
Kohno N
中科院分区：
文献类型：
--
作者：
Kawate T;Iwaya K;Koshikawa K;Moriya T;Yamasaki T;Hasegawa S;Kaise H;Fujita T;Matsuo H;Nakamura T;Ishikawa T;Hiroi S;Iguchi-Ariga SM;Ariga H;Murota K;Fujimori M;Yamamoto J;Matsubara O;Kohno N
在癌症和帕金森氏症患者中，DJ-1蛋白可能会在潜在细胞保护机制的反应受损期间分泌到血清中。为了确定乳腺癌患者血清中DJ-1蛋白的临床意义，我们检测了乳腺癌组(n=180)和非癌对照组(n=300)的血液样本。EL ISA法检测到乳腺癌组的DJ-1平均水平(42.7 ng/m L)明显高于对照组(28.3 ng/m L)(P=0.019)。根据活检组织的TNM分类、激素受体阴性状态和高Ki-67标记指数，较高的DJ-1水平与晚期临床分级显著相关；尽管DJ-1mRNA表达上调，但样本中DJ-1蛋白表达较低。经双向凝胶电泳法和免疫印迹分析，17例血标本(11例乳腺癌患者和6例非乳腺癌对照)DJ-1亚型均清晰可检出。在11例肿瘤中，等电点为6.3的异构体强度最高。相反，在6例非癌组织中，除PI6.3亚型外，其他亚型均有高表达，且乳腺癌组与对照组之间的亚型差异有统计学意义(P<0.00025)。这些数据表明，高水平的DJ-1，可能是等电点6.3的异构体，是乳腺癌的候选血清标志。
In patients with cancer and Parkinson’s disease, the DJ-1 protein may be secreted into the serum during the impaired response of the underlying cell-protective mechanisms. In order to determine the clinical significance of DJ-1 protein in the sera of breast cancer patients, we examined blood samples from a breast cancer group (n = 180) and a non-cancerous control group (n = 300). Higher levels of DJ-1 were detected in the breast cancer group (mean level, 42.7 ng/mL) than the control group (28.3 ng/mL) by ELISA (P = 0.019). Higher DJ-1 levels were significantly associated with advanced clinical grade, according to the TNM classification, negative hormone receptor status, and high Ki-67 labeling index, of biopsied materials; samples showed low DJ-1 protein expression despite upregulated DJ-1 mRNA. DJ-1 isoforms could be detected clearly in 17 blood samples (from 11 breast cancer patients, and 6 non-cancerous controls) by 2-D gel electrophoresis and immunoblot analysis. The isoform at the pI of 6.3 showed the highest intensity in all 11 cancer cases. Conversely, in the 6 non-cancerous cases, isoforms other than the pI 6.3 isoform were highly expressed, and there was a significant difference in the isoform pattern between breast cancer cases and controls (P = 0.00025). These data indicate that high levels of DJ-1, probably of isoform at pI 6.3, is a candidate serum marker of breast cancer.