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.
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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