Proteome Landscapes of Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

Yi, Xiao; Zhu, Jiang; Liu, Wei; Lu, Cong; Sun, Ping; Huang, Lingling; Nie, Xiu; Huang, Shiang; Guo, Tiannan; Zhu, Yi

doi:10.1016/j.mcpro.2023.100604

Cited by 10 publications

(5 citation statements)

References 53 publications

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“…However, considering the small number of samples tested, we further investigated additional proteomics data based on mass spectrometry. These results confirmed variable upregulation of COPS subunit proteins in HCC tissues relative to healthy adjacent tissues (Figure 3B [29], Supplementary Figure 2D [30] and Supplementary Figure 2E [31]).…”

Section: Expression Of Cops Subunits In Hcc: Associations With Clinic...supporting

confidence: 74%

“…The Human Protein Atlas (https://www.proteinatlas.org) (version 23.0), which contains more than 10 million single-cell protein expression profiles generated by immunocytochemistry and immunohistochemistry [28], was utilized to identify differences in protein expression between normal and HCC tissues and to retrieve the related literature. Here, we compared the protein expression levels of COPS subunits based on immunohistochemical images and quantitative proteomics analysis based on mass spectrometry [29][30][31].…”

Section: Differential Expression Analysis Of Copsmentioning

confidence: 99%

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COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma

Liu,

Han,

Xuan

et al. 2024

Aging

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Hepatocellular carcinoma (HCC) is among the most common deadly tumors but still lacks specific biomarkers for diagnosis, prognosis, and treatment guidance. The COP9 signalosome (COPS) is an essential regulator of the ubiquitin conjugation pathway upregulated in various cancers. We evaluated the contributions of COPS subunits to HCC tumorigenesis and their utility for prognosis. We comprehensively evaluated the tumor expression pattern and tumorigenic functions of COPS subunits using The Cancer Genome Atlas (TCGA), The Human Protein Atlas and immunohistochemistry. Kaplan–Meier, Cox regression, ROC curve, and nomogram analyses were used to assess the predictive values of COPS subunits for clinical outcome. Expression levels of COPS subunits were significantly upregulated in HCC tissues, which predicted shorter overall survival (OS). Further, Cox regression analysis identified COPS5, COPS7B, and COPS9 as independent prognostic biomarkers for OS. High mutation rates were also found in COPS subunits. Functional network analysis indicated that COPS and neighboring genes regulate ‘protein neddylation’, ‘protein deneddylation’, and ‘protein ubiquitination’. The COPS PPI included strong interactions with p53, CUL1/2/3/4, and JUN. Moreover, the correlations between COPS subunit expression levels and tumor immune cell infiltration rates were examined using TIMER, TISIDB, ssGSEA, and ESTIMATE packages. COPS subunits expression levels were positively correlated with specific tumor immune cell infiltration rates, immunoregulator expression levels, and microsatellite instability in HCC. Finally, knockout of COPS6 and COPS9 in HCC cells reduced while overexpression enhanced proliferation rate and metastasis capacity. Our study revealed that COPS potential biomarker for unfavorable HCC prognosis and indicators of immune infiltration, tumorigenicity, and metastasis.

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Section: Expression Of Cops Subunits In Hcc: Associations With Clinic...supporting

confidence: 74%

Section: Differential Expression Analysis Of Copsmentioning

confidence: 99%

COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma

Liu,

Han,

Xuan

et al. 2024

Aging

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“…The variations of collagen molecules, phosphate groups, lipid ester carbonyls, and polysaccharides were found in CCA patients. Specific lipid metabolism in HCC and abnormal extracellular pathways in CCA were found by mass spectrometry ( 50 ). RF was used to select the features and establish the model with an area under the curve (AUC) value of 0.92 and an accuracy of 90%.…”

Section: Ai and Diagnosismentioning

confidence: 99%

Application of AI on cholangiocarcinoma

Huang,

Bai,

Qiu

et al. 2024

Front. Oncol.

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Cholangiocarcinoma, classified as intrahepatic, perihilar, and extrahepatic, is considered a deadly malignancy of the hepatobiliary system. Most cases of cholangiocarcinoma are asymptomatic. Therefore, early detection of cholangiocarcinoma is significant but still challenging. The routine screening of a tumor lacks specificity and accuracy. With the application of AI, high-risk patients can be easily found by analyzing their clinical characteristics, serum biomarkers, and medical images. Moreover, AI can be used to predict the prognosis including recurrence risk and metastasis. Although they have some limitations, AI algorithms will still significantly improve many aspects of cholangiocarcinoma in the medical field with the development of computing power and technology.

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“…Primary liver cancer is the sixth most frequently diagnosed cancer and the second leading cause of cancer death worldwide in 2022, with approximately 865,000 new cases and 757,948 deaths . Liver tumorigenesis is accompanied by a suite of alterations in proteomes, − which may also manifest in circulating fluids. Previous hospital-centric studies have reported that circulating levels of several proteins were associated with the risk of liver cancer. − Yet, most plasma proteomic studies concerning liver cancer have predominantly relied on cross-sectional designs.…”

Section: Introductionmentioning

confidence: 99%

“…Unlike the genome and transcriptome, protein level regulations often show a more direct correlation with disease phenotypes. , Therefore, probing the proteome may yield novel insights into the risk of developing liver cancer. Recent technological advancements, particularly in high-throughput techniques like liquid chromatography-tandem mass spectrometry (LC-MS/MS) and data-independent acquisition (DIA) methods, have enabled detailed and high-throughput proteomic profiling. ,, These innovations allow for the simultaneous assessment of thousands of proteins with high precision, providing deeper insights into the molecular mechanisms of diseases and identification of potential biomarkers. By employing this technology in a cohort study, where instances of liver cancer emerged during follow-up, we might pinpoint circulating proteins linked to liver cancer risk.…”

Section: Introductionmentioning

confidence: 99%

Proteogenomic Analysis Identifies a Causal Association between Plasma Apolipoprotein B Levels and Liver Cancer Risk

Liu,

Yuan,

Wang

et al. 2024

J. Proteome Res.

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Liver oncogenesis is accompanied by discernible protein changes in the bloodstream. By employing plasma proteomic profiling, we can delve into the molecular mechanisms of liver cancer and pinpoint potential biomarkers. In this nested case-control study, we applied liquid chromatography-tandem mass spectrometry for proteome profiling in baseline plasma samples. Differential protein expression was determined and was subjected to functional enrichment, network, and Mendelian randomization (MR) analyses. We identified 193 proteins with notable differential levels between the groups. Of these proteins, MR analysis offered a compelling negative association between apolipoprotein B (APOB) and liver cancer. This association was further corroborated in the UK Biobank cohort: genetically predicted APOB levels were associated with a 31% (95% CI 19−42%) decreased risk of liver cancer; and phenotypic analysis indicated an 11% (95% CI 8− 14%) decreased liver cancer risk for every 0.1 g/L increase of circulating APOB levels. Multivariable MR analysis suggested that the hepatic fat content might fully mediate the APOB-liver cancer connection. In summary, we identified some plasma proteins, particularly APOB, as potential biomarkers of liver cancer. Our findings underscore the intricate link between lipid metabolism and liver cancer, offering hints for targeted prophylactic strategies and early detection.

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Proteome Landscapes of Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

Cited by 10 publications

References 53 publications

COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma

COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma

Application of AI on cholangiocarcinoma

Proteogenomic Analysis Identifies a Causal Association between Plasma Apolipoprotein B Levels and Liver Cancer Risk

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