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中国HBV相关肝细胞癌的蛋白质组学综合特征 [复制链接]

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发表于 2019-10-23 13:56 |只看该作者 |倒序浏览 |打印

SHANGHAI, Oct. 22, 2019 /PRNewswire/ -- The world-class journal Cell, an international high-impact journal, published the article "Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma in China." The research was jointly conducted and published by the teams of Dr. Jia Fan at Zhongshan Hospital, Fudan University, Dr. Hu Zhou at Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Dr. Daming Gao at the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Dr. Weiwei Shi at OrigiMed.


Graphical Abstract

To date, this is the largest cohort study on hepatocellular carcinoma (HCC) in China, especially on the multi-omics proteogenomic analysis of HBV-related HCC. As a partner of the Clinical Proteomic Tumor Analysis Consortium (CPTAC), OrigiMed conducted a comprehensive proteogenomic analysis of HBV-related HCC from a Chinese cohort, and also was the first Chinese tumor precision medicine company to publish Chinese cancer population data in Cell.

The study performed the first proteogenomic characterization of hepatitis B virus (HBV)-related HCC using paired tumors and adjacent liver tissues from 159 patients. Integrated proteogenomic analysis revealed consistency and discordance among multi-omics, activation status of key signaling pathways, and liver-specific metabolic reprogramming in HBV-related HCC.

Proteomic profiling identified three subgroups associated with clinical and molecular attributes including patient survival, tumor thrombus, genetic profile, and the liver-specific proteome. These proteomic subgroups have distinct features in metabolic reprogramming, microenvironment dysregulation, cell proliferation, and potential therapeutics.

Two prognostic biomarkers, PYCR2 and ADH1A, related to proteomic subgrouping and involved in HCC metabolic reprogramming were identified. CTNNB1 and TP53 mutation-associated signaling and metabolic profiles were revealed, among which mutated CTNNB1- associated ALDOA phosphorylation was validated to promote glycolysis and cell proliferation. The study provides a valuable resource that significantly expands the knowledge of HBV-related HCC and may eventually benefit clinical practice.

It is widely known that China is home to a large population suffering from liver cancer. According to the China Liver Cancer Big Data Report published in 2018, there are 854,000 new cases of primary liver cancer in the world every year. Among these cases, 466,000 cases (55%) are from China. The incidence of liver cancer remains high in China. Among males, liver cancer is the third most common cancer, preceded by lung cancer and stomach cancer.

HCC accounts for about 85–90% of all primary liver malignancies, and the largest attributable causes are chronic infection of hepatitis B virus (HBV), hepatitis C virus (HCV) (Sartorius et al., 2015), alcohol abuse, and metabolic syndrome. HBV is estimated to affect 292,000,000 people globally, and current antiviral therapy is not able to eliminate HBV completely. Notably, HBV-related HCC accounts for about 85% of HCC cases in China (Prevention of Infection Related Cancer (PIRCA) Group, 2019) due to the high prevalence of HBV infection.

Collectively, this study not only provides a high-quality proteogenomic resource of HBV-related HCC complementary to The Cancer Genome Atlas (TCGA), but also implicates promising prognostic and therapeutic significance and underlying regulatory mechanisms that may benefit clinical practice.

Dr. Weiwei Shi, the co-first author of this article and vice president of the Computational Oncology Department of OrigiMed said, "The importance of Multi-omics is that it can help to understand the comprehensive information of tumors from different dimensions. Benefitting from the cross-complementation among omics, we compared the relationship between different omics, which, to a large extent, made up for the shortcomings of single omics. It has been a great honor for OrigiMed to take the responsibility for the main bioinformatics analysis of liver cancer multi-omics proteogenomic data and pathological analysis of clinical liver cancer samples in this study. We hope to work more closely with clinical partners in the future, so as to provide comprehensive and accurate molecular diagnostic information for every cancer patient and help the reform of cancer treatment methods."

DOI: https://doi.org/10.1016/j.cell.2019.08.052

About OrigiMed

Established in May 2016, OrigiMed is a medical science and technology company devoted to providing comprehensive molecular diagnostic information for cancer patients leveraging next-generation sequencing technology. OrigiMed collaborates with hospitals and institutes by providing comprehensive genomic testing in our CLIA-certificated and CAP-accredited laboratory. It also partners with pharmaceutical companies all over the world throughout research, biomarker-driven drug development, and commercialization of new cancer therapies. For more information, go to www.origimed.com.


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才高八斗

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发表于 2019-10-23 13:57 |只看该作者
上海,2019年10月22日,国际影响力很高的世界级杂志《细胞》(Cell)发表了文章《中国HBV相关肝细胞癌的蛋白质组学综合特征》。这项研究是由复旦大学中山医院的贾凡博士,中国科学院上海药物研究所的胡舟博士,上海生物化学与细胞研究所的高大明博士联合进行并发表的。中国科学院生物生物学,蛋白质组学肿瘤分析联合会(CPTAC)和OrigiMed的Shiweiwei博士。
图形概要


迄今为止,这是中国最大的一项关于肝细胞癌(HCC)的队列研究,尤其是有关HBV相关HCC的多组学蛋白质组学分析。作为临床蛋白质组学肿瘤分析协会(CPTAC)的合作伙伴,OrigiMed对来自中国队列的HBV相关HCC进行了全面的蛋白质组学分析,并且是第一家在Cell中发布中国癌症人群数据的中国肿瘤精密医学公司。

该研究使用配对的肿瘤和来自159名患者的相邻肝组织进行了乙型肝炎病毒(HBV)相关的HCC的首次蛋白质组学表征。整合的蛋白质组学分析显示,在HBV相关的HCC中,多组学,关键信号通路的激活状态以及肝脏特异性代谢重编程之间存在一致性和不一致。

蛋白质组学分析确定了与临床和分子属性相关的三个亚组,包括患者生存率,肿瘤血栓,遗传谱和肝脏特异性蛋白质组。这些蛋白质组在代谢重编程,微环境失调,细胞增殖和潜在的治疗方法中具有独特的特征。

鉴定了两个与蛋白质组有关并参与HCC代谢重编程的预后生物标志物PYCR2和ADH1A。揭示了CTNNB1和TP53突变相关的信号和代谢谱,其中经突变的CTNNB1相关的ALDOA磷酸化被证实可促进糖酵解和细胞增殖。该研究提供了宝贵的资源,可极大地扩展与HBV相关的HCC的知识,并可能最终有益于临床实践。

众所周知,中国是众多肝癌患者的故乡。根据2018年发布的《中国肝癌大数据报告》,每年全球有85.4万例新发原发性肝癌病例。在这些案例中,有466,000案例(55%)来自中国。在中国肝癌的发病率仍然很高。在男性中,肝癌是第三大常见癌症,其次是肺癌和胃癌。

HCC占所有原发性肝恶性肿瘤的约85–90%,最大的可归因是乙型肝炎病毒(HBV),丙型肝炎病毒(HCV)的慢性感染(Sartorius等,2015),酗酒和代谢综合症。估计HBV会影响全球2.92亿人,目前的抗病毒治疗不能完全消除HBV。值得注意的是,由于HBV感染率很高,HBV相关的HCC约占中国HCC病例的85%(感染相关癌症预防(PIRCA)组,2019)。

总的来说,这项研究不仅提供了与癌症基因组图谱(TCGA)互补的,与HBV相关的HCC的高质量蛋白质组学资源,而且还暗示了有希望的预后和治疗意义以及潜在的有益于临床实践的调节机制。

本文的共同第一作者,OrigiMed计算肿瘤学部副总裁史伟伟博士说:“多组学的重要性在于,它可以帮助理解不同维度的肿瘤的全面信息。通过组学之间的交叉互补,我们比较了不同组学之间的关系,这些关系在很大程度上弥补了单个组学的缺点,这是OrigiMed承担起肝脏主要生物信息学分析的责任,这是我的荣幸这项研究中的癌症多组学蛋白质组基因组学数据和临床肝癌病理分析,我们希望将来与临床合作伙伴更加紧密地合作,以便为每位癌症患者提供全面而准确的分子诊断信息,并帮助进行肝癌的改革。癌症治疗方法。”

DOI:https://doi.org/10.1016/j.cell.2019.08.052
关于OrigiMed

OrigiMed成立于2016年5月,是一家医疗科技公司,致力于利用下一代测序技术为癌症患者提供全面的分子诊断信息。 OrigiMed通过在我们的CLIA认证和CAP认可的实验室中提供全面的基因组测试,与医院和研究所合作。 它还在研究,生物标记物驱动的药物开发以及新的癌症疗法的商业化方面与世界各地的制药公司合作。 有关更多信息,请访问www.origimed.com
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