Integrated proteogenomic characterization of medullary thyroid carcinoma.
Integrated proteogenomic characterization of medullary thyroid carcinoma.
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DOI：
10.1038/s41421-022-00479-y
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发表时间：
2022-11-08
期刊：
影响因子：
33.5
通讯作者：
Wei, Wenjun
中科院分区：
文献类型：
--
作者：
Shi, Xiao;Sun, Yaoting;Shen, Cenkai;Zhang, Yan;Shi, Rongliang;Zhang, Fan;Liao, Tian;Lv, Guojun;Zhu, Zhengcai;Jiao, Lianghe;Li, Peng;Xu, Tiansheng;Qu, Ning;Huang, Naisi;Hu, Jiaqian;Zhang, Tingting;Gu, Yanzi;Qin, Guangqi;Guan, Haixia;Pu, Weilin;Li, Yuan;Geng, Xiang;Zhang, Yan;Chen, Tongzhen;Huang, Shenglin;Zhang, Zhikang;Ge, Shuting;Wang, Wu;Xu, Weibo;Yu, Pengcheng;Lu, Zhongwu;Wang, Yulong;Guo, Liang;Wang, Yu;Guo, Tiannan;Ji, Qinghai;Wei, Wenjun
甲状腺髓样癌是一种罕见的神经内分泌恶性肿瘤，起源于甲状腺滤泡旁细胞（C细胞）。在这里，我们通过全外显子组测序，RNA测序，DNA甲基化阵列，蛋白质组学和磷酸化蛋白质组学分析，展示了102个MTC的综合多组学景观。综合分析确定BRAF和NF 1作为新的驱动基因，除了充分表征的RET和RAS原癌基因。MTC的基于蛋白质组的分层揭示了三种分子异质性亚型，命名为：（1）代谢型，（2）基底型和（3）间充质型，其在遗传驱动因子，表观遗传修饰谱，临床病理因素和临床结局方面不同。此外，我们探索了每个蛋白质组亚型的假定治疗靶点，并发现两个腱蛋白家族成员TNC/TNXB可能作为MTC的潜在预后生物标志物。总的来说，我们的研究扩展了MTC生物学和治疗漏洞的知识，这可能是未来调查这种恶性肿瘤的重要资源。
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy derived from parafollicular cells (C cells) of the thyroid. Here we presented a comprehensive multi-omics landscape of 102 MTCs through whole-exome sequencing, RNA sequencing, DNA methylation array, proteomic and phosphoproteomic profiling. Integrated analyses identified BRAF and NF1 as novel driver genes in addition to the well-characterized RET and RAS proto-oncogenes. Proteome-based stratification of MTCs revealed three molecularly heterogeneous subtypes named as: (1) Metabolic, (2) Basal and (3) Mesenchymal, which are distinct in genetic drivers, epigenetic modification profiles, clinicopathologic factors and clinical outcomes. Furthermore, we explored putative therapeutic targets of each proteomic subtype, and found that two tenascin family members TNC/TNXB might serve as potential prognostic biomarkers for MTC. Collectively, our study expands the knowledge of MTC biology and therapeutic vulnerabilities, which may serve as an important resource for future investigation on this malignancy.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
46.9
作者：
通讯作者：
--
DOI：
10.1093/bioinformatics/btr670
发表时间：
2012-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Boeva V;Popova T;Bleakley K;Chiche P;Cappo J;Schleiermacher G;Janoueix-Lerosey I;Delattre O;Barillot E
通讯作者：
Barillot E
影响因子：
50.3
作者：
Fishbein L;Leshchiner I;Walter V;Danilova L;Robertson AG;Johnson AR;Lichtenberg TM;Murray BA;Ghayee HK;Else T;Ling S;Jefferys SR;de Cubas AA;Wenz B;Korpershoek E;Amelio AL;Makowski L;Rathmell WK;Gimenez-Roqueplo AP;Giordano TJ;Asa SL;Tischler AS;Cancer Genome Atlas Research Network;Pacak K;Nathanson KL;Wilkerson MD
通讯作者：
Wilkerson MD