scholarly journals Bcl-2 Associated Athanogene 2 (BAG2) is Associated With Progression and Prognosis of Hepatocellular Carcinoma: A Bioinformatics-Based Analysis

2021 ◽  
Vol 27 ◽  
Author(s):  
Xi Zhang ◽  
Junjun Zhang ◽  
Yang Liu ◽  
Jie Li ◽  
Juan Tan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Ribosome Biogenesis ◽  
Bioinformatics Analysis ◽  
Progression Free Survival ◽  
Cell Counting ◽  
Free Survival ◽  
Prognostic Analysis ◽  
Worse Prognosis ◽  
Disease Specific

Background: Bcl-2 associated athanogene2 (BAG2) is reported to act as an oncogene or a tumor-suppressor in tumors in a context-dependent way; however, its function in hepatocellular carcinoma (HCC) remains unclear.Methods: Immunohistochemistry (IHC) staining, cell counting kit-8 (CCK-8) assay, apoptotic assay, cell invasion assay and a set of bioinformatics tools were integrated to analyze the role of BAG2 in hepatocellular carcinoma.Results: BAG2 was significantly up-regulated in HCC. Prognostic analysis indicated that HCC patients with high expression of BAG2 had significantly shorter overall survival, progression free survival and disease specific survival. Besides, silencing BAG2 in HCC cells impaired cell proliferation, facilitated apoptosis and repressed invasion of the cells. Bioinformatics analysis showed that BAG2 might regulate ribosome biogenesis in HCC.Conclusion: This study revealed that the up-regulated BAG2 in HCC was associated with a worse prognosis and might favor the progression of the disease.

The Role of the Albumin-Bilirubin Score for Predicting the Outcomes in Japanese Patients with Advanced Hepatocellular Carcinoma Treated with Ramucirumab: A Real-World Study

Oncology ◽  
2020 ◽  
pp. 1-12
Author(s):  
Takeshi Hatanaka ◽  
Atsushi Naganuma ◽  
Mitsuhiko Shibasaki ◽  
Tatsuya Kohga ◽  
Yosuke Arai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Real World ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Low Incidence ◽  
Number Of Cycles

<b><i>Aim:</i></b> The aim of this retrospective study was to investigate the efficacy and safety of ramucirumab treatment under real-world conditions and to clarify the role of albumin-bilirubin (ALBI) score in predicting outcomes. <b><i>Methods:</i></b> Between June 2019 and May 2020, a total of 16 patients with advanced hepatocellular carcinoma (HCC) treated with ramucirumab in Gunma Saiseikai Maebashi Hospital and its affiliated hospitals was included. <b><i>Results:</i></b> The median age was 71 (interquartile range [IQR] 65–74) years old, and 12 patients (75.0%) were male. The modified ALBI (mALBI) grade was 1, 2a, and 2b at baseline in 4 (25.0%), 3 (18.8%), and 9 patients (56.3%), respectively. The Barcelona Clinic Liver Cancer stage was intermediate and advanced stage in 1 (6.3%) and 15 patients (93.8%), respectively. The serum α-fetoprotein at baseline was 4,911 (IQR 2,091–17,377) ng/mL. The disease control rate in patients with mALBI grade1 + 2a was significantly higher than in those with mALBI grade 2b (100 vs. 28.6%, <i>p</i> = 0.028). The patients with mALBI grade 1 + 2a had a significantly better overall survival (OS) and longer progression-free survival (PFS) than those with mALBI grade 2b (median OS 6.7 vs. 3.0 months; <i>p</i> = 0.036, median PFS 7.5 vs. 1.4 months; <i>p</i> = 0.002). The number of cycles of ramucirumab treatment was significantly correlated with the ALBI score (<i>r</i> = −0.452, <i>p</i> = 0.030). The patients with mALBI grade 1 + 2a showed a low incidence of adverse events (AEs) and discontinuation due to AEs. <b><i>Conclusions:</i></b> Advanced HCC patients with mALBI grade 1 + 2a may be a good indication for ramucirumab treatment.

Nano-Gold PCR in Detection of TERT Methylation and Its Correlation with Hepatitis B-Related Hepatocellular Carcinoma

2021 ◽  
Vol 17 (7) ◽  
pp. 1284-1292
Author(s):  
Jie Zhao ◽  
Li Li ◽  
Liying Guo ◽  
Rui Wang ◽  
Yan Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Tnm Staging ◽  
Intrahepatic Metastasis ◽  
Conventional Pcr ◽  
Hilar Lymph Node ◽  
Free Survival ◽  
Nano Gold ◽  
Worse Prognosis

This study aimed to introduce nano-gold PCR for detection of TERT methylation, and explore the correlation between TERT methylation and prognosis of hepatocellular carcinoma (HCC). From March 2016 to March 2018, 154 HBV carriers treated in our hospital were enrolled in the study and divided into HCC (68 cases), cirrhosis (45 cases) and chronic hepatitis (CH) groups (41 cases) based on clinical disease. HCC patients were further divided into methylation (30 cases) and non-methylation (38 cases) subgroup based on methylation status of the TERT. TERT methylation of HCC specimens were 44.12% and 35.24% by nano-PCR and conventional PCR, respectively. The TERT methylation and TERT expression in HCC specimens were higher than for cirrhosis and CH specimens. A significant positive correlation was observed between TERT methylation and TERT expression. AFP, Edmondson classification, tumor size, hilar lymph node and intrahepatic metastasis, and TNM staging in the methylation group were higher than in non-methylation group. Further, overall survival and progression-free survival were significantly shorter. Nano-gold PCR is more sensitive in detecting TERT methylation. As CHB progresses, TERT methylation increases. Greater methylation of the gene is associated with worse prognosis in HCC patients.

scholarly journals Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma

Liver Cancer ◽  
2021 ◽  
pp. 1-10
Author(s):  
Petros Fessas ◽  
Muntaha Naeem ◽  
Matthias Pinter ◽  
Thomas U. Marron ◽  
David Szafron ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint Inhibitor ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Tumor Burden ◽  
Free Survival ◽  
Programmed Cell Death 1 ◽  
Predictive Role ◽  
Pugh Class

<b><i>Background and Rationale:</i></b> Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC. <b><i>Methods:</i></b> In a large international cohort of 450 ICI recipients from Europe, North America, and Asia, we categorized patients according to timing of ATB focusing on exposure within −30 to +30 days from ICI (early immunotherapy period [EIOP]). EIOP was evaluated in association with overall survival (OS), progression-free survival (PFS), and best radiologic response using RECIST 1.1 criteria. <b><i>Results:</i></b> Our study comprised mostly cirrhotic (329, 73.3%) males (355, 79.1%) with a Child-Turcotte Pugh class of A (332, 73.9%), receiving ICI after 1 therapy line (251, 55.9%) for HCC of Barcelona clinic liver cancer stage C (325, 72.4%). EIOP (<i>n</i> = 170, 37.9%) was independent of baseline clinicopathologic features of HCC and correlated with longer PFS (6.1 vs. 3.7 months, log-rank <i>p</i> = 0.0135). EIOP+ patients had similar OS, overall response, and disease control rates (DCRs) compared to EIOP. The effect of EIOP persisted in landmark time analyses and in multivariable models, confirming the independent predictive role of EIOP in influencing PFS following adjustment for covariates reflective of tumor burden, liver function, and ICI regimen administered. In patients receiving programmed cell death-1 receptor/ligand inhibitors monotherapy, EIOP was also associated with higher DCRs (61.4% vs. 50.9%, <i>p</i> = 0.0494). <b><i>Conclusions:</i></b> Unlike other oncological indications, ATB in the 30 days before or after ICI initiation is associated with improved benefit from immunotherapy, independent of disease and treatment-related features. Evaluation of the immune microbiologic determinants of response to ICI in HCC warrants further investigation.

scholarly journals Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression

2021 ◽  
Vol 9 ◽  
Author(s):  
Goutham Venkata Naga Davuluri ◽  
Chien-Chin Chen ◽  
Yen-Cheng Chiu ◽  
Hung-Wen Tsai ◽  
Hung-Chih Chiu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stromal Cells ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Tumor Associated Macrophages ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Secretion Mode ◽  
Secretory Autophagy

Galectin-1 (Gal-1) is a secretory lectin with pro-tumor activities and is associated strongly with hepatocellular carcinoma (HCC) development. Although Gal-1 is a well-known soluble pro-tumor factor in the tumor microenvironment (TME), the secretion mode of Gal-1 is not clearly defined. On the other hand, in addition to cancer cells, Gal-1 is widely expressed in tumor stromal cells, including tumor-associated macrophages (TAMs). TAMs are a significant component of stromal cells in TME; however, their contributions in producing Gal-1 to TME are still not explored. Here we reveal that TAMs can actively secrete Gal-1 in response to stimuli of HCC cells. Gal-1 produced by TAMs leads to an increase of the systemic level of Gal-1 and HCC tumor growth in mice. Mechanistically, TLR2-dependent secretory autophagy is found to be responsible for Gal-1 secretion from TAMs. Gal-1 acts as a cargo of autophagosomes to fuse with multivesicular bodies via Rab11 and VAMP7-mediated vesicle trafficking before being secreted. This autophagy-regulated Gal-1 secretion in TAMs correlates to poor overall survival and progression-free survival rates of HCC patients. Our findings uncover the secretion mode of Gal-1 via secretory autophagy and highlight the pathological role of TAM-produced Gal-1 in HCC progression.

Sorafenib and hepatocellular carcinoma: is alpha-fetoprotein a biomarker predictive of tumor biology and primary resistance?

2021 ◽  
Author(s):  
Francesca Negri ◽  
Letizia Gnetti ◽  
Giuseppe Pedrazzi ◽  
Enrico Maria Silini ◽  
Camillo Porta
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Tumor Biology ◽  
Progression Free Survival ◽  
Alpha Fetoprotein ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Resistance ◽  
Free Survival ◽  
Vegf Signaling

Background: Alpha-fetoprotein (AFP) is the only biomarker with proven prognostic value in advanced hepatocellular carcinoma. Preliminary data indicate crosstalk between AFP and VEGF signaling. Methods: The authors looked at 69 patients with advanced hepatocellular carcinoma who were previously tested for VEGFR2 expression, had available baseline AFP serum concentrations and were treated with sorafenib within clinical trials. Results: Shorter progression-free survival and overall survival were associated with increased AFP level and elevated VEGFR2 staining. At multivariate analysis of AFP level was the only independent prognostic factor for progression-free survival and overall survival. Conclusion: The authors' study confirms the adverse prognostic role of elevated baseline AFP and also suggests a possible role of AFP in primary resistance to sorafenib therapy.

scholarly journals Efficacy and Safety of Lenvatinib in Hepatocellular Carcinoma Patients with Liver Transplantation: A Case-Control Study

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4584
Author(s):  
Yen-Yang Chen ◽  
Chao-Long Chen ◽  
Chih-Che Lin ◽  
Chih-Chi Wang ◽  
Yueh-Wei Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Progression Free Survival ◽  
Comparable Efficacy ◽  
Control Group ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Significant Difference ◽  
The Difference

Tumor recurrence is the most common cause of death in hepatocellular carcinoma (HCC) patients who received liver transplantation (LT). Recently, lenvatinib was approved for the systemic treatment of unresectable HCC patients; however, the role of lenvatinib in HCC patients after LT remains unclear. There were 56 patients with recurrent HCC after LT from 2008 to 2018 in our institute, and 10 patients who received lenvatinib were identified. Additionally, to understand the difference in the clinical impact of lenvatinib in the LT and non-LT settings, 25 HCC patients without LT who underwent lenvatinib treatment were identified from our HCC database and regarded as the control group. In the LT group, partial response was 20% and stable disease was 50%, resulting in a disease control rate of 70%; the median progression-free survival (PFS), time to treatment failure (TTF) and overall survival (OS) were 3.7, 3.6 and 16.4 months, respectively. Adverse events (AEs) were predominantly grade 1–2 in severity, and the majority of patients tolerated the side effects. There was no significant difference in PFS/OS, and we observed a similar pattern of AEs between these two groups. Our study confirms the comparable efficacy and safety of lenvatinib in HCC patients with LT and non-LT in clinical practice.

scholarly journals A Novel Epigenetic Machine Learning Model to Define Risk of Progression for Hepatocellular Carcinoma Patients

2021 ◽  
Vol 22 (3) ◽  
pp. 1075
Author(s):  
Luca Bedon ◽  
Michele Dal Bo ◽  
Monica Mossenta ◽  
Davide Busato ◽  
Giuseppe Toffoli ◽  
...  
Keyword(s):  
Machine Learning ◽  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Progression Free Survival ◽  
Low Risk ◽  
Functional Enrichment ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Of Progression ◽  
Risk Patients

Although extensive advancements have been made in treatment against hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfied. It is now clearly established that extensive epigenetic changes act as a driver in human tumors. This study exploits HCC epigenetic deregulation to define a novel prognostic model for monitoring the progression of HCC. We analyzed the genome-wide DNA methylation profile of 374 primary tumor specimens using the Illumina 450 K array data from The Cancer Genome Atlas. We initially used a novel combination of Machine Learning algorithms (Recursive Features Selection, Boruta) to capture early tumor progression features. The subsets of probes obtained were used to train and validate Random Forest models to predict a Progression Free Survival greater or less than 6 months. The model based on 34 epigenetic probes showed the best performance, scoring 0.80 accuracy and 0.51 Matthews Correlation Coefficient on testset. Then, we generated and validated a progression signature based on 4 methylation probes capable of stratifying HCC patients at high and low risk of progression. Survival analysis showed that high risk patients are characterized by a poorer progression free survival compared to low risk patients. Moreover, decision curve analysis confirmed the strength of this predictive tool over conventional clinical parameters. Functional enrichment analysis highlighted that high risk patients differentiated themselves by the upregulation of proliferative pathways. Ultimately, we propose the oncogenic MCM2 gene as a methylation-driven gene of which the representative epigenetic markers could serve both as predictive and prognostic markers. Briefly, our work provides several potential HCC progression epigenetic biomarkers as well as a new signature that may enhance patients surveillance and advances in personalized treatment.

scholarly journals Efficacy of lenvatinib for unresectable hepatocellular carcinoma based on background liver disease etiology: multi-center retrospective study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Atsushi Hiraoka ◽  
Takashi Kumada ◽  
Toshifumi Tada ◽  
Joji Tani ◽  
Kazuya Kariyama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Liver Disease ◽  
Hazard Analysis ◽  
Progression Free Survival ◽  
Significant Prognostic Factor ◽  
Disease Etiology ◽  
Alcoholic Fatty Liver ◽  
Free Survival ◽  
Significant Difference

AbstractIt was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child–Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.

Clinical Outcomes of 2nd- and 3rd-Line Regorafenib for Advanced Hepatocellular Carcinoma

Oncology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Kensuke Naruto ◽  
Tomokazu Kawaoka ◽  
Kei Amioka ◽  
Yutaro Ogawa ◽  
Kikukawa Chihiro ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Outcomes ◽  
Median Overall Survival ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Free Survival ◽  
Line Therapy ◽  
Unresectable Hepatocellular Carcinoma

<b><i>Introduction:</i></b> This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. <b><i>Methods:</i></b> In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. <b><i>Results:</i></b> There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. <b><i>Conclusion:</i></b> Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.

scholarly journals Transarterial Radioembolization of Hepatocellular Carcinoma, Liver-Dominant Hepatic Colorectal Cancer Metastases, and Cholangiocarcinoma Using Yttrium90 Microspheres: Eight-Year Single-Center Real-Life Experience

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 122
Author(s):  
Julie Pellegrinelli ◽  
Olivier Chevallier ◽  
Sylvain Manfredi ◽  
Inna Dygai-Cochet ◽  
Claire Tabouret-Viaud ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Progression Free Survival ◽  
Single Center ◽  
Free Survival ◽  
Risk Of Death ◽  
Transarterial Radioembolization ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

Liver tumors are common and may be unamenable to surgery or ablative treatments. Consequently, other treatments have been devised. To assess the safety and efficacy of transarterial radioembolization (TARE) with Yttrium-90 for hepatocellular carcinoma (HCC), liver-dominant hepatic colorectal cancer metastases (mCRC), and cholangiocarcinoma (CCA), performed according to current recommendations, we conducted a single-center retrospective study in 70 patients treated with TARE (HCC, n = 44; mCRC, n = 20; CCA, n = 6). Safety and toxicity were assessed using the National Cancer Institute Common Terminology Criteria. Treatment response was evaluated every 3 months on imaging studies using Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. The median delivered dose was 1.6 GBq, with SIR-Spheres® or TheraSphere® microspheres. TARE-related grade 3 adverse events affected 17.1% of patients. Median follow-up was 32.1 months. Median progression-free survival was 5.6 months and median overall time from TARE to death was 16.1 months and was significantly shorter in men. Progression-free survival was significantly longer in women (HR, 0.49; 95%CI, 0.26–0.90; p = 0.031). Risk of death or progression increased with the number of systemic chemotherapy lines. TARE can be safe and effective in patients with intermediate- or advanced-stage HCC, CCA, or mCRC refractory or intolerant to appropriate treatments.

Sign in / Sign up

Export Citation Format

Share Document