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蛋白质组学表征揭示了鼻咽癌分化的分子图谱。

Proteomic Characterization Reveals a Molecular Portrait of Nasopharyngeal Carcinoma Differentiation.

作者信息

Xiao Zhefeng, Li Maoyu, Li Guoqing, Fu Ying, Peng Fang, Chen Yongheng, Chen Zhuchu

机构信息

Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.

Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China;; State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, P.R. China;; Collaborative Innovation Center for Cancer Medicine (CICCM), Guangzhou, Guangdong, P. R. China.

出版信息

J Cancer. 2017 Feb 11;8(4):570-577. doi: 10.7150/jca.17414. eCollection 2017.

Abstract

Nasopharyngeal carcinoma (NPC) is categorized into three different differentiated subtypes by World Health Organization (WHO). Based on an earlier comparative proteomic database of the three histological subtypes, the study was to deepen our understanding of molecular mechanisms associated with NPC differentiation through bio-information mining. Among the three subtypes were 194 differentially expressed proteins (DEPs) of 725 identified proteins. Two DEPs, heat shock protein family B (small) member 1 (HSPB1) and keratin 5 (KRT5), were validated in a series of NPC tissue samples by using immunohistochemistry. Quantified protein families including keratins, S100 proteins (S100s) and heat shock proteins exhibited characteristic expression alterations. Comparisons of predicted bio-function activation states among different subtypes, including formation of cellular protrusion, metastasis, cell death, and viral infections, were conducted. Canonical pathway analysis inferred that Rho GTPases related signaling pathways regulated the motility and invasion of dedifferentiated NPC. In conclusion, the study explored the proteomic characteristics of NPC differentiation, which could deepen our knowledge of NPC tumorigenesis and allow the development of novel targets of therapeutic and prognostic value in NPC.

摘要

世界卫生组织(WHO)将鼻咽癌(NPC)分为三种不同的分化亚型。基于这三种组织学亚型早期的比较蛋白质组数据库,本研究旨在通过生物信息挖掘加深我们对与NPC分化相关分子机制的理解。在这三种亚型中,725种已鉴定蛋白质中有194种差异表达蛋白质(DEP)。通过免疫组织化学在一系列NPC组织样本中验证了两种DEP,即热休克蛋白家族B(小)成员1(HSPB1)和角蛋白5(KRT5)。包括角蛋白、S100蛋白(S100s)和热休克蛋白在内的定量蛋白质家族表现出特征性的表达改变。对不同亚型之间预测的生物功能激活状态进行了比较,包括细胞突起形成、转移、细胞死亡和病毒感染。典型通路分析推断,Rho GTPases相关信号通路调节去分化NPC的运动性和侵袭性。总之,本研究探索了NPC分化的蛋白质组特征,这可以加深我们对NPC肿瘤发生的认识,并有助于开发具有治疗和预后价值的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b0a/5370501/efd7f694f19e/jcav08p0570g001.jpg

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