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Quantitative Secretome Analysis Reveals Clinical Values of Carbonic Anhydrase II in Hepatocellular C

本站小编 Free考研考试/2022-01-03

Early detection and intervention are key strategies to reduce mortality, increase long-term survival, and improve the therapeutic effects of hepatocellular carcinoma (HCC) patients. Herein, the isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative proteomic strategy was used to study the secretomes in conditioned media from HCC cancerous tissues, surrounding noncancerous tissues, and distal noncancerous tissues to identify diagnostic and prognostic biomarkers for HCC. In total, 22 and 49 dysregulated secretory proteins were identified in the cancerous and surrounding noncancerous tissues, respectively, compared with the distal noncancerous tissues. Among these proteins, carbonic anhydrase II (CA2) was identified to be significantly upregulated in the secretome of cancerous tissues; correspondingly, the serum concentrations of CA2 were remarkably increased in HCC patients compared with that in normal populations. Interestingly, a significant increase of serum CA2 in recurrent HCC patients after radical resection was also confirmed compared with HCC patients without recurrence, and the serum level of CA2 could act as an independent prognostic factor for time to recurrence and overall survival. Regarding the mechanism, the secreted CA2 enhances the migration and invasion of HCC cells by activating the epithelial mesenchymal transition pathway. Taken together, this study identified a novel biomarker for HCC diagnosis and prognosis, and provided a valuable resource of HCC secretome for investigating serological biomarkers.
早期诊断和干预是降低肝细胞癌(HCC)死亡率、增加其远期生存率、提高治疗效果的关键。因此,我们对HCC手术切除的来源于同一个病人的癌、癌旁和远癌组织分别进行体外培养,应用iTRAQ定量蛋白质组技术开展分泌蛋白质组的系统分析,筛选HCC诊断和预后的生物标志物。研究结果发现,与远癌组织相比,在癌组织和癌旁组织中分别鉴定了22和49个失调的分泌蛋白。其中,碳酸酐酶II (CA2)在癌组织中的分泌显著高于癌旁组织和远癌组织,并且HCC病人的血清CA2浓度也明显高于正常人群。有价值的是,复发HCC病人在根治性切除术后血清CA2浓度水平显著高于未复发的HCC病人;且血清CA2水平可作为独立的预后危险因素,显著影响病人的无复发生存(TTR)和总生存(OS)。在机制研究发现,分泌性CA2可以促进肝癌细胞的侵袭和转移,并激活上皮间充质转化(EMT)信号通路。综上所述,本研究鉴定了一种新的可用于HCC诊断和预后判断的新型生物标志物,并为研究肝癌分泌组蛋白组和血清学生物标志物提供了宝贵的数据资源。





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http://gpb.big.ac.cn/articles/download/838
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