Predictive biomarkers for systemic therapy of hepatocellular carcinoma

Moldogazieva, N. T.; Zavadskiy, S. P.; Sologova, Susanna S.; Mokhosoev, Innokenty M.; Terentiev, A. A.

doi:10.1080/14737159.2021.1987217

Cited by 24 publications

(18 citation statements)

References 163 publications

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“…However, we did not perform further systematic analysis on the correlations between C1QBP protein levels and HCC patient survival nor the expression pattern of C1QBP in HCC tissues, due to the lack of patient databases for the evaluation of protein expression in a large scale manner. Therefore, we would like to check the protein expression of C1QBP in our own HCC patient cohort with detailed clinical parameters in the future investigation, as clinically immunohistochemical analysis on the expression of key protein markers such as Ki67 6 is widely applied for the diagnosis or/and prognosis of HCC patients.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, unveiling the mechanisms for HCC progression is of great significance for the identification of potential therapeutic targets or agents, which might be further developed for adjuvant therapeutic strategies. Moreover, although a variety of biomarkers including MTOR and RAF1 6 have been identified for aiding to the prognosis of HCC patients, exploring biomarkers with higher effectiveness for combined prognostic application is still required.…”

Section: Introductionmentioning

confidence: 99%

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The Mitochondrial Protein C1QBP Promotes Hepatocellular Carcinoma Progression by Enhancing Cell Survival, Migration and Invasion

Hou¹,

Lu²,

Wang³

et al. 2022

J. Cancer

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Backgrounds: Hepatocellular carcinoma (HCC) is a major type of death-causing cancer whose pathological mechanisms are not fully understood. In addition, the identification of effective biomarkers for HCC prognosis is in emergency. Although a variety of studies have shown that Complement C11 binding protein (C1QBP) may play a tumor-promoting or tumor-suppressive role in cancer, the functions and mechanisms of C1QBP in HCC progression are under-investigating. Methods and results: Bioinformatic approaches were employed for checking the expression of C1QBP in HCC patient samples and the association between C1QBP mRNA expression and survival rates of patients with HCC or the promoter methylation of C1QBP . MTT analysis, PI/Annexin V staining, transwell and metabolic flux assays were performed to examine the effects of C1QBP on proliferation, apoptosis, migration, invasion, and oxidative phosphorylation of HCC cells. In the present study, we observed that C1QBP is lower expressed in HCC samples and cell lines. Moreover, high levels of C1QBP were associated with unfavorable outcomes of HCC patients. Loss-of-function assays showed that proliferation, migration and invasion of HCC cells were mitigated while cell apoptosis was augmented upon the loos of C1QBP. Moreover, the oxidative phosphorylation was moderately decreased when C1QBP was depleted. Furthermore, we also investigated the methylation status and copy number variation of C1QBP and analyzed their correlation with its mRNA expression in HCC patients. Finally, we suggested that C1QBP is correlated with genes encoding ribosome RPL-related proteins and mitochondrial MRPL-related proteins in HCC patients. Conclusions: C1QBP is correlated with a poor prognosis of HCC patients and promotes the survival, migration and invasion of HCC cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Mitochondrial Protein C1QBP Promotes Hepatocellular Carcinoma Progression by Enhancing Cell Survival, Migration and Invasion

Hou¹,

Lu²,

Wang³

et al. 2022

J. Cancer

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“…Among them, Sorafenib is the most widely used (75)(76)(77). In order to overcome the shortcomings of Sorafenib, newly molecular targeted drugs including Regorafenib, Lenvatinib and Cabozantinib have been approved for marketing one after another (78)(79)(80). Although it is currently believed that these drugs are generally superior to Sorafenib, these agents (lenvatinib, regorafenib, and carbozantinib) have the same chemical core structure (1-(4-(pyridin-4-yloxy)phenyl) urea) with sorafenib (81).…”

Section: Discussionmentioning

confidence: 99%

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

et al. 2021

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BAY-876 is an effective antagonist of the Glucose transporter type 1 (GLUT1) receptor, a mediator of aerobic glycolysis, a biological process considered a hallmark of hepatocellular carcinoma (HCC) together with cell proliferation, drug-resistance, and metastasis. However, the clinical application of BAY-876 has faced many challenges. In the presence study, we describe the formulation of a novel microcrystalline BAY-876 formulation. A series of HCC tumor models were established to determine not only the sustained release of microcrystalline BAY-876, but also its long-acting antitumor activity. The clinical role of BAY-876 was confirmed by the increased expression of GLUT1, which was associated with the worse prognosis among advanced HCC patients. A single dose of injection of microcrystalline BAY-876 directly in the HCC tissue achieved sustained localized levels of Bay-876. Moreover, the single injection of microcrystalline BAY-876 in HCC tissues not only inhibited glucose uptake and prolonged proliferation of HCC cells, but also inhibited the expression of epithelial-mesenchymal transition (EMT)-related factors. Thus, the microcrystalline BAY-876 described in this study can directly achieve promising localized effects, given its limited diffusion to other tissues, thereby reducing the occurrence of potential side effects, and providing an additional option for advanced HCC treatment.

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“…This was surprising, because mass spectrometry is highly appropriate for elucidating the changes arising in the phosphoproteome as a consequence of the activity exerted by tyrosine kinase inhibitors. This was the case when we explored the activity of the aforementioned inhibitors in other cancer types, such as cholangiocarcinoma, breast cancer, hepatocellular cancer, or gastric cancer [ 261 , 262 , 263 , 264 ]. However, the conclusions and findings may not be extrapolated to BC; thus, further research is strongly needed.…”

Section: Proteomics In the Therapy Of Bladder Cancermentioning

confidence: 99%

Proteomics as a Complementary Technique to Characterize Bladder Cancer

López-Cortés

Vázquez‐Estévez

Fernandez

et al. 2021

Cancers

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Bladder cancer (BC) is the most common tumor of the urinary tract and is conventionally classified as either non-muscle invasive or muscle invasive. In addition, histological variants exist, as organized by the WHO-2016 classification. However, innovations in next-generation sequencing have led to molecular classifications of BC. These innovations have also allowed for the tracing of major tumorigenic pathways and, therefore, are positioned as strong supporters of precision medicine. In parallel, immunohistochemistry is still the clinical reference to discriminate histological layers and to stage BC. Key contributions have been made to enlarge the panel of protein immunomarkers. Moreover, the analysis of proteins in liquid biopsy has also provided potential markers. Notwithstanding, their clinical adoption is still low, with very few approved tests. In this context, mass spectrometry-based proteomics has remained a step behind; hence, we aimed to develop them in the community. Herein, the authors introduce the epidemiology and the conventional classifications to review the molecular classification of BC, highlighting the contributions of proteomics. Then, the advances in mass spectrometry techniques focusing on maintaining the integrity of the biological structures are presented, a milestone for the emergence of histoproteomics. Within this field, the review then discusses selected proteins for the comprehension of the pathophysiological mechanisms of BC. Finally, because there is still insufficient knowledge, this review considers proteomics as an important source for the development of BC therapies.

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Predictive biomarkers for systemic therapy of hepatocellular carcinoma

Cited by 24 publications

References 163 publications

The Mitochondrial Protein C1QBP Promotes Hepatocellular Carcinoma Progression by Enhancing Cell Survival, Migration and Invasion

The Mitochondrial Protein C1QBP Promotes Hepatocellular Carcinoma Progression by Enhancing Cell Survival, Migration and Invasion

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

Proteomics as a Complementary Technique to Characterize Bladder Cancer

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