Early diagnostic value of survivin and its alternative splice variants in breast cancer.
Early diagnostic value of survivin and its alternative splice variants in breast cancer.
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DOI：
10.1186/1471-2407-14-176
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发表时间：
2014-03-12
期刊：
影响因子：
3.8
通讯作者：
Wall NR
中科院分区：
文献类型：
--
作者：
Khan S;Bennit HF;Turay D;Perez M;Mirshahidi S;Yuan Y;Wall NR
凋亡抑制蛋白Survivin及其剪接变异体在乳腺癌组织中差异表达。我们之前的工作表明，Survivin是通过称为外体的膜结合小泡从肿瘤细胞释放出来的。因此，我们推测，对血清Survivin及其剪接变异体的分析可能为乳腺癌的早期诊断提供一种新的生物标志物。我们收集了40例乳腺癌患者和10例对照患者的血清，这些患者在治疗后5年内无病。此外，对来自同一40例患者的23例配对乳腺癌组织进行了剪接变异分析。用ELISA法分析血清中Survivin的水平，并使用商用的ExoQuick试剂盒从该血清中分离外切体，随后进行Western blotting和免疫组织化学。所有乳腺癌样本中Survivin水平均显著高于对照组(p <； 0.05)，其中癌症患者血清中的外切体数量显著高于对照组(p <； 0.01)。Survivin和Survivin-∆EX3剪接变异体在血清外体中的表达和定位相同，而Survivin-2B蛋白在外体中的表达存在差异。同样，Survivin和Survivin-∆EX3蛋白在本研究评估的所有乳腺癌组织中都是主要的表达形式，而Survivin-2B在不同的癌症分期中的表达差异更大。在这项研究中，我们首次表明，像Survivin一样，Survivin剪接变体也外包装在乳腺癌患者的血清中，模仿我们在乳腺癌组织中也报道的Survivin剪接变体模式。Exosomal-Survivin的差异表达，特别是Survivin-2B，可以作为早期乳腺癌患者的诊断和/或预后标志物，如果你愿意的话，可以作为“液体活检”。此外，更彻底地了解这一重要的抗细胞凋亡途径的作用可能会导致乳腺癌患者潜在治疗药物的开发。
The inhibitor of apoptosis (IAP) protein Survivin and its splice variants are differentially expressed in breast cancer tissues. Our previous work showed Survivin is released from tumor cells via small membrane-bound vesicles called exosomes. We, therefore, hypothesize that analysis of serum exosomal Survivin and its splice variants may provide a novel biomarker for early diagnosis of breast cancer. We collected sera from forty breast cancer patients and ten control patients who were disease free for 5 years after treatment. In addition, twenty-three paired breast cancer tumor tissues from those same 40 patients were analyzed for splice variants. Serum levels of Survivin were analyzed using ELISA and exosomes were isolated from this serum using the commercially available ExoQuick kit, with subsequent Western blots and immunohistochemistry performed. Survivin levels were significantly higher in all the breast cancer samples compared to controls (p < 0.05) with exosome amounts significantly higher in cancer patient sera compared to controls (p < 0.01). While Survivin and Survivin-∆Ex3 splice variant expression and localization was identical in serum exosomes, differential expression of Survivin-2B protein existed in the exosomes. Similarly, Survivin and Survivin-∆Ex3 proteins were the predominant forms detected in all of the breast cancer tissues evaluated in this study, whereas a more variable expression of Survivin-2B level was found at different cancer stages. In this study we show for the first time that like Survivin, the Survivin splice variants are also exosomally packaged in the breast cancer patients’ sera, mimicking the survivin splice variant pattern that we also report in breast cancer tissues. Differential expression of exosomal-Survivin, particularly Survivin-2B, may serve as a diagnostic and/or prognostic marker, a “liquid biopsy” if you will, in early breast cancer patients. Furthermore, a more thorough understanding of the role of this prominent antiapoptotic pathway could lead to the development of potential therapeutics for breast cancer patients.
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影响因子：
4.8
作者：
Savina, A;Furl치n, M;Colombo, MI
通讯作者：
Colombo, MI
影响因子：
3.7
作者：
Khan S;Jutzy JM;Valenzuela MM;Turay D;Aspe JR;Ashok A;Mirshahidi S;Mercola D;Lilly MB;Wall NR
通讯作者：
Wall NR
胃癌中不同生存变异的表达：源于苏属-2b在肿瘤进展中的作用的第一线索。
影响因子：
8.8
作者：
Krieg, A;Mahotka, C;Krieg, T;Grabsch, H;Muller, W;Takeno, S;Suschek, C V;Heydthausen, M;Gabbert, H E;Gerharz, C D
通讯作者：
Gerharz, C D
影响因子：
8
作者：
Caldas, H;Jiang, YY;Altura, RA
通讯作者：
Altura, RA
影响因子：
8.4
作者：
O'Brien, Keith;Rani, Sweta;O'Driscoll, Lorraine
通讯作者：
O'Driscoll, Lorraine