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Annals of Hepatology 2023In hepatocellular carcinoma (HCC), the prognosis of patients with microvascular invasion (MVI) is poor. Therefore, in this study, we established and evaluated the...
INTRODUCTION AND OBJECTIVES
In hepatocellular carcinoma (HCC), the prognosis of patients with microvascular invasion (MVI) is poor. Therefore, in this study, we established and evaluated the performance of a novel nomogram to predict MVI in patients with HCC.
MATERIALS AND METHODS
We retrospectively obtained clinical data of 497 patients with HCC who underwent hepatectomy at Liaoning Cancer Hospital from November 1, 2018, to November 4, 2021. The patients (n = 497) were randomized in a 7:3 ratio into the training cohort (TC, n = 349) and the validation cohort (VC, n = 148). We performed Least Absolute Shrinkage and Selection Operator (LASSO) and univariate as well as multivariate logistic regression analyses (ULRA, MRLA) on patients in the TC to identify factors independently predicting MVI.
RESULTS
Preoperative FIB-4, AFU, AFP levels, liver cirrhosis, and non-smooth tumor margin were independent risk factors for preoperative MVI prediction. The C-index of the TC, VC, and the entire cohort was 0.846, 0.786, and 0.829, respectively. The calibration curves demonstrated the outstanding agreement between predicted MVI incidences by our model and the actual MVI risk. Decision curve analysis (DCA) confirmed the significance of our predictive model in clinical settings. The Kaplan-Meier (KM) survival curve showed that the recurrence-free survival (RFS) and overall survival (OS) of patients in the high-MVI risk group were poor compared to those in the low-MVI risk group.
CONCLUSIONS
We constructed and evaluated the performance of the novel nomogram for predicting MVI risk. Our predictive model could adequately predict MVI risk and aid clinicians in selecting appropriate therapeutic strategies for patients.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Nomograms; Female; Male; Middle Aged; Retrospective Studies; Neoplasm Invasiveness; Hepatectomy; Microvessels; Risk Factors; Aged; Prognosis; Predictive Value of Tests; Risk Assessment
PubMed: 37479060
DOI: 10.1016/j.aohep.2023.101136 -
Hepatology International Oct 2023To effectively prevent recurrence, improve the prognosis and increase the survival rate of primary liver cancer (PLC) patients with radical cure, the Chinese Society of...
To effectively prevent recurrence, improve the prognosis and increase the survival rate of primary liver cancer (PLC) patients with radical cure, the Chinese Society of Hepatology, Chinese Medical Association, invited clinical experts and methodologists to develop the Consensus on the Tertiary Prevention of Primary Liver Cancer, which was based on the clinical and scientific advances on the risk factors, histopathology, imaging finding, clinical manifestation, and prevention of recurrence of PLC. The purpose is to provide a current basis for the prevention, surveillance, early detection and diagnosis, and the effective measures of PLC recurrence.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Consensus; Tertiary Prevention; Prognosis
PubMed: 37369911
DOI: 10.1007/s12072-023-10549-2 -
Current Treatment Options in Oncology Dec 2023The treatment of neuroendocrine neoplasm (NEN) liver metastases involves a multidisciplinary approach that includes liver-directed therapies (LDT) and systemic... (Review)
Review
The treatment of neuroendocrine neoplasm (NEN) liver metastases involves a multidisciplinary approach that includes liver-directed therapies (LDT) and systemic treatments, such as peptide receptor radionuclide therapy (PRRT). LDT has demonstrated efficacy in rapidly reducing tumor bulk, improving symptoms, and delaying disease progression. Interventional radiologists should be consulted prior to switching therapy for patients with progressive or symptomatic neuroendocrine tumor liver metastases. Long-term follow-up data on the safety of Yttrium-90 radioembolization before and after PRRT remain limited. Therefore, a more conservative approach may be to preferentially employ transarterial embolization (TAE) or transarterial chemoembolization (TACE) for patients' somatostatin receptor-avid disease who may be future candidates for PRRT. Notable exceptions where radioembolization may be a preferred treatment strategy may be patients with history of biliary tract instrumentation, asymmetric unilobar disease distribution, and rapidly progressive diffuse liver involvement. Selection of local treatment modality, sequencing, and combination of LDT with systemic therapy require further investigation.
Topics: Humans; Neuroendocrine Tumors; Chemoembolization, Therapeutic; Liver Neoplasms; Carcinoma, Hepatocellular; Receptors, Peptide; Radioisotopes; Treatment Outcome
PubMed: 38100020
DOI: 10.1007/s11864-023-01152-6 -
Redox Biology Jul 2023Glutamine is critical for tumor progression, and restriction of its availability is emerging as a potential therapeutic strategy. The metabolic plasticity of tumor cells...
Glutamine is critical for tumor progression, and restriction of its availability is emerging as a potential therapeutic strategy. The metabolic plasticity of tumor cells helps them adapting to glutamine restriction. However, the role of cholesterol metabolism in this process is relatively unexplored. Here, we reported that glutamine deprivation inhibited cholesterol synthesis in hepatocellular carcinoma (HCC). Reactivation of cholesterol synthesis enhanced glutamine-deprivation-induced cell death of HCC cells, which is partially duo to augmented NADPH depletion and lipid peroxidation. Mechanistically, glutamine deprivation induced lipophagy to transport cholesterol from lipid droplets (LDs) to endoplasmic reticulum (ER), leading to inhibit SREBF2 maturation and cholesterol synthesis, and maintain redox balance for survival. Glutamine deprivation decreased mTORC1 activity to induce lipophagy. Importantly, administration of U18666A, CQ, or shTSC2 viruses further augmented GPNA-induced inhibition of xenograft tumor growth. Clinical data supported that glutamine utilization positively correlated with cholesterol synthesis, which is associated with poor prognosis of HCC patients. Collectively, our study revealed that cholesterol synthesis inhibition is required for the survival of HCC under glutamine-restricted tumor microenvironment.
Topics: Humans; Carcinoma, Hepatocellular; Glutamine; Liver Neoplasms; Cell Line, Tumor; Autophagy; Cholesterol; Tumor Microenvironment
PubMed: 37150151
DOI: 10.1016/j.redox.2023.102732 -
Advanced Science (Weinheim,... Apr 2024Recent studies suggest that circular RNA (circRNA)-mediated post-translational modification of RNA-binding proteins (RBP) plays a pivotal role in metastasis of...
Recent studies suggest that circular RNA (circRNA)-mediated post-translational modification of RNA-binding proteins (RBP) plays a pivotal role in metastasis of hepatocellular carcinoma (HCC). However, the specific mechanism and potential clinical therapeutic significance remain vague. This study attempts to profile the regulatory networks of circRNA and RBP using a multi-omics approach. Has_circ_0006646 (circ0006646) is an unreported circRNA in HCC and is associated with a poor prognosis. Silencing of circ0006646 significantly hinders metastasis in vivo. Mechanistically, circ0006646 prevents the interaction between nucleolin (NCL) and the E3 ligase tripartite motif-containing 21 to reduce the proteasome-mediated degradation of NCL via K48-linked polyubiquitylation. Furthermore, the change of NCL expression is proven to affect the phosphorylation levels of multiple proteins and inhibit p53 translation. Moreover, patient-derived tumor xenograft and lentivirus injection, which is conducted to simulate clinical treatment confirmed the potential therapeutic value. Overall, this study describes the integrated multi-omics landscape of circRNA-mediated NCL ubiquitination degradation in HCC metastasis and provides a novel therapeutic target.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; Humans; RNA, Circular; Ubiquitination; Mice; Animals; RNA-Binding Proteins; Cell Line, Tumor; Nucleolin; Neoplasm Metastasis; Tripartite Motif Proteins; Disease Models, Animal; Multiomics
PubMed: 38357830
DOI: 10.1002/advs.202306915 -
Current Oncology (Toronto, Ont.) Apr 2024Neuroendocrine tumors (NETs) are a heterogeneous class of cancers, predominately occurring in the gastroenteropancreatic system, which pose a growing health concern with... (Review)
Review
Neuroendocrine tumors (NETs) are a heterogeneous class of cancers, predominately occurring in the gastroenteropancreatic system, which pose a growing health concern with a significant rise in incidence over the past four decades. Emerging from neuroendocrine cells, these tumors often elicit paraneoplastic syndromes such as carcinoid syndrome, which can manifest as a constellation of symptoms significantly impacting patients' quality of life. The prognosis of NETs is influenced by their tendency for metastasis, especially in cases involving the liver, where the estimated 5-year survival is between 20 and 40%. Although surgical resection remains the preferred curative option, challenges emerge in cases of neuroendocrine tumors with liver metastasis (NELM) with multifocal lobar involvement, and many patients may not meet the criteria for surgery. Thus, minimally invasive and non-surgical treatments, such as locoregional therapies, have surfaced. Overall, these approaches aim to prioritize symptom relief and aid in overall tumor control. This review examines locoregional therapies, encompassing catheter-driven procedures, ablative techniques, and radioembolization therapies. These interventions play a pivotal role in enhancing progression-free survival and managing hormonal symptoms, contributing to the dynamic landscape of evolving NELM treatment. This review meticulously explores each modality, presenting the current state of the literature on their utilization and efficacy in addressing NELM.
Topics: Humans; Neuroendocrine Tumors; Liver Neoplasms
PubMed: 38668057
DOI: 10.3390/curroncol31040154 -
International Journal of Biological... 2023Although apatinib is a promising drug for the treatment of liver cancer, the underlying drug resistance mechanism is still unclear. Here, we constructed...
Although apatinib is a promising drug for the treatment of liver cancer, the underlying drug resistance mechanism is still unclear. Here, we constructed apatinib-resistant HepG2 cells. We then characterized the epigenomic, transcriptomic, and proteomic landscapes both in apatinib-resistant and non-resistant HepG2 cells. Differential expression, ATAC-seq, and proteomic data analyses were performed. We found that the cell cycle related protein RB1 may play an essential role in the process of apatinib resistant to hepatocarcinoma. Moreover, there were extensive variations at the transcriptome, epigenetic, and proteomic level. Finally, quantitative PCR (qPCR) and western blot analysis showed that expression level of RB1 in apatinib-resistant cell as well as the samples of patients in progressive disease were significantly lower than that in controls. Those results also showed that the RB1 pathway inhibitors CDK2-IN-73 and Palbociclib could relieve the resistance of apatinib resistant cells. Our results further enhance our understanding of the anti-tumorigenic and anti-angiogenic efficacy of apatinib in liver cancer and provide a novel perspective regarding apatinib resistance. Furthermore, we proved that CDKN2B inhibition of RB1 signaling promoted apatinib resistance in hepatocellular carcinoma. Those findings have greatly important biological significance for the resistance of apatinib and the treatment of liver cancer.
Topics: Humans; Carcinoma, Hepatocellular; Cell Line, Tumor; Liver Neoplasms; Multiomics; Proteomics; Retinoblastoma Binding Proteins; Ubiquitin-Protein Ligases; Drug Resistance, Neoplasm
PubMed: 37781033
DOI: 10.7150/ijbs.83862 -
ELife Oct 2023CD133 (prominin 1) is widely viewed as a cancer stem cell marker in association with drug resistance and cancer recurrence. Herein, we report that with impaired...
CD133 (prominin 1) is widely viewed as a cancer stem cell marker in association with drug resistance and cancer recurrence. Herein, we report that with impaired RTK-Shp2-Ras-Erk signaling, heterogenous hepatocytes form clusters that manage to divide during mouse liver regeneration. These hepatocytes are characterized by upregulated CD133 while negative for other progenitor cell markers. Pharmaceutical inhibition of proliferative signaling also induced CD133 expression in various cancer cell types from multiple animal species, suggesting an inherent and common mechanism of stress response. Super-resolution and electron microscopy localize CD133 on intracellular vesicles that apparently migrate between cells, which we name 'intercellsome.' Isolated CD133 intercellsomes are enriched with mRNAs rather than miRNAs. Single-cell RNA sequencing reveals lower intracellular diversity (entropy) of mitogenic mRNAs in Shp2-deficient cells, which may be remedied by intercellular mRNA exchanges between CD133 cells. CD133-deficient cells are more sensitive to proliferative signal inhibition in livers and intestinal organoids. These data suggest a mechanism of intercellular communication to compensate for intracellular signal deficit in various cell types.
Topics: Mice; Animals; Neoplasm Recurrence, Local; Hepatocytes; Liver Neoplasms; Cell Communication; RNA, Messenger
PubMed: 37846866
DOI: 10.7554/eLife.86824 -
Transplant International : Official... 2023Liver transplantation offers the best chance of cure for most patients with non-metastatic hepatocellular carcinoma (HCC). Although not all patients with HCC are...
Liver transplantation offers the best chance of cure for most patients with non-metastatic hepatocellular carcinoma (HCC). Although not all patients with HCC are eligible for liver transplantation at diagnosis, some can be downstaged using locoregional treatments such as ablation and transarterial chemoembolization. These aforementioned treatments are being applied as bridging therapies to keep patients within transplant criteria and to avoid them from dropping out of the waiting list while awaiting a liver transplant. Moreover, immunotherapy might have great potential to support downstaging and bridging therapies. To address the contemporary status of downstaging, bridging, and immunotherapy in liver transplantation for HCC, European Society of Organ Transplantation (ESOT) convened a dedicated working group comprised of experts in the treatment of HCC to review literature and to develop guidelines pertaining to this cause that were subsequently discussed and voted during the Transplant Learning Journey (TLJ) 3.0 Consensus Conference that took place in person in Prague. The findings and recommendations of the working group on Downstaging, Bridging and Immunotherapy in Liver Transplantation for Hepatocellular Carcinoma are presented in this article.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Transplantation; Treatment Outcome; Chemoembolization, Therapeutic; Neoadjuvant Therapy; Neoplasm Staging; Immunotherapy
PubMed: 37779513
DOI: 10.3389/ti.2023.11648 -
Frontiers in Immunology 2023
Topics: Humans; Liver Transplantation; Liver Neoplasms; Transplants
PubMed: 37781357
DOI: 10.3389/fimmu.2023.1276566