A multi-omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma.
A multi-omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma.
复制标题
一项多组学研究描绘了食管鳞状细胞癌的新分子特征和治疗靶点
DOI：
10.1002/ctm2.538
复制
发表时间：
2021-09
影响因子：
10.6
通讯作者：
Chen WL
中科院分区：
文献类型：
--
作者：
Jin X;Liu L;Wu J;Jin X;Yu G;Jia L;Wang F;Shi M;Lu H;Liu J;Liu D;Yang J;Li H;Ni Y;Luo Q;Jia W;Wang W;Chen WL
食管鳞状细胞癌(ESCC)是食道癌的主要组织亚型，预后较差。在这里，我们对治疗初期的人ESCC和配对的正常邻近组织(队列1，n=924)进行了全面的转录、蛋白质组、磷蛋白质组和代谢组学表征，以努力确定ESCC的新的分子易感性和潜在的治疗靶点。整合分析揭示了一小群与ESCC转录后和翻译后调节活跃相关的基因。通过使用蛋白质组、磷蛋白质组和代谢组学数据，与癌症病因学密切相关的ESCC相关信号和代谢通路的网络被揭开。值得注意的是，蛋白质组和磷蛋白质组数据的综合分析准确地指出，参与RNA转录、加工和代谢的某些途径在ESCC中受到刺激。重要的是，确定了与ESCC预后密切相关的蛋白质。通过纳入ESCC患者队列2(n=41)，3个排名靠前的预后蛋白X-脯氨酸氨基肽酶3(XPNPEP3)、溴域PhD指状转录因子(BPTF)和纤维蛋白(FBL)在ESCC中的表达增加。在这些预后蛋白中，只有众所周知的核仁甲基转移酶FBL对ESCC细胞的体外和体内生长是必不可少的。此外，一项使用ESCC患者队列3(n=100)的验证性研究表明，FBL的高表达预示着不利的患者生存。最后，描述了常见的癌症/睾丸抗原和已建立的癌症驱动因素和激酶，所有这些都可以指导治疗决策。总之，我们的多组学分析描绘了与ESCC病理生物学相关的新的分子特征，涉及表观遗传、转录后、翻译后和代谢特征，并揭示了具有治疗潜力的新的分子脆弱性。1.揭示了ESCC的一个新的分子特征，它涉及到转录后和翻译后的主动调控。2.描述了与ESCC相关的信号和代谢途径、组学数据之间的网络、常见的癌症/睾丸抗原以及已建立的癌症驱动因素和激酶。3.发现了与ESCC预后密切相关的蛋白，并对一种新的预后蛋白--纤维蛋白(FBL)进行了进一步的验证和功能研究，发现其与患者预后呈负相关。
Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment‐naive ESCC and paired normal adjacent tissues (cohort 1, n = 24) in an effort to identify new molecular vulnerabilities for ESCC and potential therapeutic targets. Integrative analysis revealed a small group of genes that were related to the active posttranscriptional and posttranslational regulation of ESCC. By using proteomic, phosphoproteomic, and metabolomic data, networks of ESCC‐related signaling and metabolic pathways that were closely linked to cancer etiology were unraveled. Notably, integrative analysis of proteomic and phosphoproteomic data pinpointed that certain pathways involved in RNA transcription, processing, and metabolism were stimulated in ESCC. Importantly, proteins with close linkage to ESCC prognosis were identified. By enrolling an ESCC patient cohort 2 (n = 41), three top‐ranked prognostic proteins X‐prolyl aminopeptidase 3 (XPNPEP3), bromodomain PHD finger transcription factor (BPTF), and fibrillarin (FBL) were verified to have increased expression in ESCC. Among these prognostic proteins, only FBL, a well‐known nucleolar methyltransferase, was essential for ESCC cell growth in vitro and in vivo. Furthermore, a validation study using an ESCC patient cohort 3 (n = 100) demonstrated that high FBL expression predicted unfavorable patient survival. Finally, common cancer/testis antigens and established cancer drivers and kinases, all of which could direct therapeutic decisions, were characterized. Collectively, our multi‐omics analyses delineated new molecular features associated with ESCC pathobiology involving epigenetic, posttranscriptional, posttranslational, and metabolic characteristics, and unveiled new molecular vulnerabilities with therapeutic potential for ESCC. 1. A new molecular feature of ESCC that involves both active posttranscriptional and posttranslational regulation was unveiled. 2. ESCC‐related signaling and metabolic pathways, networks among omics data, and common cancer/testis antigens along with established cancer drivers and kinases were delineated. 3. Proteins with close linkage to ESCC prognosis were discovered, and a new prognostic protein, fibrillarin (FBL), was further validated, functionally studied, and found to correlate negatively with patient outcomes.
登录
查看更多内容
SF3B3 对 EZH2 前体 mRNA 的选择性剪接有助于肾癌的致瘤潜力
DOI：
10.1158/1078-0432.ccr-16-2020
发表时间：
2017-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Chen K;Xiao H;Zeng J;Yu G;Zhou H;Huang C;Yao W;Xiao W;Hu J;Guan W;Wu L;Huang J;Huang Q;Xu H;Ye Z
通讯作者：
Ye Z
通过多区域全外显子组测序对食管鳞状细胞癌及其癌前病变进行基因组比较。
影响因子：
16.6
作者：
Chen XX;Zhong Q;Liu Y;Yan SM;Chen ZH;Jin SZ;Xia TL;Li RY;Zhou AJ;Su Z;Huang YH;Huang QT;Huang LY;Zhang X;Zhao YN;Yun JP;Wu QL;Lin DX;Bai F;Zeng MS
通讯作者：
Zeng MS
影响因子：
20.3
作者：
Chen, Wen-Lian;Wang, Jing-Han;Jia, Wei
通讯作者：
Jia, Wei
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J
影响因子：
7.2
作者：
Duronio, Robert J.;Xiong, Yue
通讯作者：
Xiong, Yue