Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

Brunetti, Oronzo; Gaspar, António; Licchetta, Antonella; Longo, Vito; Calabrese, Angela; Argentiero, Antonella; Delcuratolo, Sabina; Solimando, Antonio Giovanni; Casadei-Gardini, Andrea; Silvestris, Nicola

doi:10.3390/medicina55100707

Cited by 57 publications

(41 citation statements)

References 73 publications

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“…Sorafenib is an oral multi-targeted tyrosine kinase inhibitor (TKI) targeting PDGFR, vascular endothelial growth factor (VEGFR), fibroblast growth factor receptor (FGFR), Raf, which is a gold quality standard in the first line treatment of advanced HCC patients. Cancer biomarkers have been widely used for prediction of prognosis and treatment response in certain tumors [58,59]. Predictive biomarkers can be best explored in the setting of properly designed clinical trials, and it is important to develop biomarkers to narrow down the subgroup of the patients who have a survival benefit from sorafenib treatment.…”

Section: Discussionmentioning

confidence: 99%

A novel ETV6-miR-429-CRKL regulatory circuitry contributes to aggressiveness of hepatocellular carcinoma

Guo

Gao

Zhao

et al. 2020

J Exp Clin Cancer Res

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Background: Tumor metastasis is one of the main causes of the high mortality of hepatocellular carcinoma (HCC). E-Twenty Six variant gene 6 (ETV6) is a strong transcriptional repressor, associated with the development and progression of tumors. However, the exact role and underlying mechanism of ETV6 in HCC remain unclear. Methods: Western blotting, quantitative real-time PCR and immunohistochemistry were used to detect the expression levels of ETV6, CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) and miR-429 in HCC tissues and cells; Transwell chamber and F-actin cytoskeleton staining assay to examine the effects of ETV6 and CRKL deregulation on the migration, invasion and cytoskeleton of HCC cells; Co-immunoprecipitation assay to determine the interaction between CRKL and ETV6; Chromatin immunoprecipitation assay to investigate the interaction between ETV6 and miR-429. Results: We established a novel ETV6-miR-429-CRKL regulatory circuitry contributes to HCC metastasis. ETV6 and CRKL were frequently increased, while miR-429 was downregulated in both hepatocarcinoma tissues and hepatocarcinoma cells. Moreover, ETV6 upregulation was positively correlated with CRKL upregulation, and two negative correlations were also established for ETV6 and CRKL upregulation with miR-429 downregulation in both hepatocarcinoma patients' tumorous tissues and hepatocarcinoma cells. Functional investigations revealed that overexpression and knockdown of ETV6 was remarkably effective in promoting and suppressing HCC cell migration, invasion, cytoskeleton F-actin expression and arrangement, whereas, CRKL overexpression exhibited similar effects to the overexpression of ETV6. Mechanistically, ETV6 negatively regulates miR-429 expression by directly binding to the promoter region of miR-429; miR-429 negatively regulates CRKL expression by selectively targeting CRKL-3′-UTR; ETV6 directly binds to CRKL and positively regulates its expression, which in turn CRKL positively regulates ETV6 expression.

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Section: Discussionmentioning

confidence: 99%

A novel ETV6-miR-429-CRKL regulatory circuitry contributes to aggressiveness of hepatocellular carcinoma

Guo

Gao

Zhao

et al. 2020

J Exp Clin Cancer Res

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“…Previous studies reported that an inflammatory microenvironment, circulating immune cells, and cytokines etc. play a significant role in the prognosis of HCC [41,42]. For example, the B-type Raf kinase (BRAF) mutation, one of the prognostic factors, could play a role in the response to tyrosine kinase inhibitors [43].…”

Section: Discussionmentioning

confidence: 99%

Early Change in the Plasma Levels of Circulating Soluble Immune Checkpoint Proteins in Patients with Unresectable Hepatocellular Carcinoma Treated by Lenvatinib or Transcatheter Arterial Chemoembolization

Odagiri

Hoang

Thủy

et al. 2020

Cancers

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Immune checkpoint inhibitors, combined with anti-angiogenic agents or locoregional treatments (e.g., transarterial chemoembolization (TACE)), are expected to become standard-of-care for unresectable hepatocellular carcinoma (HCC). We measured the plasma levels of 16 soluble checkpoint proteins using multiplexed fluorescent bead-based immunoassays in patients with HCC who underwent lenvatinib (n = 24) or TACE (n = 22) treatment. In lenvatinib-treated patients, plasma levels of sCD27 (soluble cluster of differentiation 27) decreased (p = 0.040) and levels of sCD40 (p = 0.014) and sTIM-3 (p < 0.001) were increased at Week 1, while levels of sCD27 (p < 0.001) were increased significantly at Weeks 2 through 4. At Week 1 of TACE, in addition to sCD27 (p = 0.028), sCD40 (p < 0.001), and sTIM-3 (soluble T-cell immunoglobulin and mucin domain–3) (p < 0.001), levels of sHVEM (soluble herpesvirus entry mediator) (p = 0.003), sTLR-2 (soluble Toll-like receptor 2) (p = 0.009), sCD80 (p = 0.036), sCTLA-4 (soluble cytotoxic T-lymphocyte antigen 4) (p = 0.005), sGITR (soluble glucocorticoid-induced tumor necrosis factor receptor) (p = 0.030), sGITRL (soluble glucocorticoid-induced TNFR-related ligand) (p = 0.090), and sPD-L1 (soluble programmed death-ligand 1) (p = 0.070) also increased. The fold-changes in soluble checkpoint receptors and their ligands, including sCTLA-4 with sCD80/sCD86 and sPD-1 (soluble programmed cell death domain–1) with sPD-L1 were positively correlated in both the lenvatinib and TACE treatment groups. Our results suggest that there are some limited differences in immunomodulatory effects between anti-angiogenic agents and TACE. Further studies from multicenters may help to identify an effective combination therapy.

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“…Some other lncRNAs, such as XIST, HOST2, HOXA-AS2, CCHE1, and AFAP1-AS1, can induce and accelerate cell proliferation, while inhibiting the apoptosis of HCC cells [33]. This feature might be useful as a therapeutic target of HCC, especially as an alternative to the patients who show chemoresistance for the chemotherapeutic drugs [6][7][8]56].…”

Section: Lncrnas Associated With Both Chronic Liver Disease and Hccmentioning

confidence: 99%

“…Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with a poor prognosis and low survival rates [4,5]. Despite advances in the understanding of the molecular mechanisms of HCC, the overall low survival time, high rates of metastasis, postsurgical recurrence, and chemoresistance are still unsolved problems [5][6][7][8]. Hepatic fibrosis is a major risk factor for HCC, and it is a continuous wound-healing process that leads to the dysregulation of extracellular matrix (ECM) proteins and the distortion of normal liver architecture [9].…”

Section: Introductionmentioning

confidence: 99%

LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma

Kim

Park

Lee

2020

IJMS

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Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral hepatitis, has only recently been considered in scientific research. While extensive studies on the pathogenesis of the development of HCC from hepatic fibrosis have been conducted, their regulatory molecular mechanisms are still only partially understood. The underlying mechanisms related to lncRNAs leading to HCC from chronic liver diseases and cirrhosis have not yet been entirely elucidated. Therefore, elucidating the functional roles of lncRNAs in chronic liver disease and HCC can contribute to a better understanding of the molecular mechanisms, and may help in developing novel diagnostic biomarkers and therapeutic targets for HCC, as well as in preventing the progression of chronic liver disease to HCC. Here, we comprehensively review and briefly summarize some lncRNAs that participate in both hepatic fibrosis and HCC.

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Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

Cited by 57 publications

References 73 publications

A novel ETV6-miR-429-CRKL regulatory circuitry contributes to aggressiveness of hepatocellular carcinoma

A novel ETV6-miR-429-CRKL regulatory circuitry contributes to aggressiveness of hepatocellular carcinoma

Early Change in the Plasma Levels of Circulating Soluble Immune Checkpoint Proteins in Patients with Unresectable Hepatocellular Carcinoma Treated by Lenvatinib or Transcatheter Arterial Chemoembolization

LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma

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