Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma

Jiang, Ying; Sun, Aihua; Zhao, Yang; Ying, Wantao; Sun, Hui‐Chuan; Yang, Xin‐Rong; Xing, Baocai; Sun, Wei; Lang, Ren; Hu, Bo; Li, Chaoying; Zhang, Li; Qin, Guangrong; Zhang, Menghuan; Chen, Ning; Zhang, Manli; Huang, Yin; Zhou, Jinan; Zhao, Yan; Liu, Mingwei; Zhu, Xiao‐Dong; Qiu, Yang; Sun, Yanjun; Huang, Cheng; Yan, Meng; Wang, Tong; Liu, Wei; Tian, Fang; Xu, Huali; Zhou, Jian; Wu, Zhenyu; Shi, Tieliu; Zhu, Weimin; Qin, Jun; Xie, Lu; Fan, Jia; Qian, Xiaohong; He, Fuchu

doi:10.1038/s41586-019-0987-8

Cited by 659 publications

(671 citation statements)

References 63 publications

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“…These results were validated at the mRNA level by real‐time PCR and at the protein level by IHC (Fig. B,C), which was also confirmed by the RNAseq data from TCGA‐LIHC and proteomic data from the Chinese Human Proteome Project (Supporting Fig. A,B,G).…”

Section: Discussionsupporting

confidence: 65%

Tumor‐Derived Peptidoglycan Recognition Protein 2 Predicts Survival and Antitumor Immune Responses in Hepatocellular Carcinoma

et al. 2020

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Background and Aims Hepatocellular carcinoma (HCC) is linked to immunosuppression. Relieving immunosuppression has been an attractive strategy to improve the efficacy of cancer immunotherapy. Peptidoglycan recognition protein 2 (PGLYRP2) is a pattern recognition receptor which is specifically expressed in liver and implicated in the regulation of innate immunity and immunosurveillance. However, the role of hepatic PGLYRP2 in modulating immune responses against HCC remains to be investigated. Approach and Results In this study, we investigated whether PGLYRP2 is able to influence HCC progression through regulating host antitumor immune responses. We demonstrated that PGLYRP2 was down‐regulated in HCC, which was linked with poor prognosis in patients (P < 0.001). PGLYRP2 overexpression in HCC cells significantly enhanced antitumor immune responses in immune‐competent mice and elevated immune response rates of peripheral blood mononuclear cells against HCC. Mechanistically, DNA methyltransferase 3A–mediated promoter hypermethylation was responsible for the down‐regulation of PGLYRP2 in HCC. PGLYRP2 promoted production of chemokine (C‐C motif) ligand 5 (CCL5) in HCC through binding to the CCL5 promoter, which contributed to the enhanced antitumor immunity. Conclusions We provide evidence that tumor‐derived PGLYRP2 acts as a candidate biomarker for adequate immune response against HCC and improved patient outcomes, indicating the importance of hepatic PGLYRP2 in cancer immunosurveillance and in designing immunotherapeutic approaches.

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Section: Discussionsupporting

confidence: 65%

Tumor‐Derived Peptidoglycan Recognition Protein 2 Predicts Survival and Antitumor Immune Responses in Hepatocellular Carcinoma

et al. 2020

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“…We observed a significant upregulation of most examined OTU subfamily DUBs, including OTUB2, OTUD7A, OTUD6B, OTUD3, OTUD7B, ALG13, OTUB1, and OTULIN (Table S1 and Figure S1A, Supporting Information). Additionally, the results of expression analysis on the data of Chinese Human Proteome Project (CNHPP) [ 31 ] (110 paired tumor and nontumor tissues of clinical early‐stage HCC) showed consistently upregulation of protein level of OTUs (including OTUD7B, OTUD6B, ALG13, OTUB1, OTULIN) in HCC tissues (Table S2 and Figure S1B, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Deubiquitylase OTUD6B Governs pVHL Stability in an Enzyme‐Independent Manner and Suppresses Hepatocellular Carcinoma Metastasis

et al. 2020

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“…HBV-associated HCC cohort containing 110 paired tumor and nontumor tissues demonstrated increased TGF-b genes and increased cholesterol metabolism in HCC compared with non-tumor tissue [41].…”

Section: Trends In Molecular Medicinementioning

confidence: 99%

Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma

Chen

Gingold

2019

Trends in Molecular Medicine

186

135

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Hepatocellular carcinoma (HCC) is an inflammation-induced and chemotherapy-resistant cancer. Dysregulated signaling in the transforming growth factor beta (TGF-b) pathway plays a central role in inflammation, fibrogenesis, and immunomodulation in the HCC microenvironment. This review dissects the genetic landscape of the TGF-b superfamily genes in HCC and discusses the essential effects of this pathway on the tumor immune microenvironment. We highlight the TGF-b signature as a potential biomarker for identifying individualized immunotherapeutic approaches in HCC. An improved understanding of the detailed mechanisms of liver cancer immunogenicity and the specific role of TGF-b in mediating immunotherapy resistance in HCC will provide important insights into HCC immune escape and promote the development of biomarker-derived combination immunotherapies for HCC.

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Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma

Cited by 659 publications

References 63 publications

Tumor‐Derived Peptidoglycan Recognition Protein 2 Predicts Survival and Antitumor Immune Responses in Hepatocellular Carcinoma

Tumor‐Derived Peptidoglycan Recognition Protein 2 Predicts Survival and Antitumor Immune Responses in Hepatocellular Carcinoma

Deubiquitylase OTUD6B Governs pVHL Stability in an Enzyme‐Independent Manner and Suppresses Hepatocellular Carcinoma Metastasis

Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma

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