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1.
J Clin Oncol ; : JCO2100608, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648352

RESUMO

PURPOSE: In a previous phase II trial, hepatic arterial infusion chemotherapy (HAIC) with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) yielded higher treatment responses than transarterial chemoembolization (TACE) in large unresectable hepatocellular carcinoma. We aimed to compare the overall survival of patients treated with FOLFOX-HAIC versus TACE as first-line treatment in this population. METHODS: In this randomized, multicenter, open-label trial, adults with unresectable hepatocellular carcinoma (largest diameter ≥ 7 cm) without macrovascular invasion or extrahepatic spread were randomly assigned 1:1 to FOLFOX-HAIC (oxaliplatin 130 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2,400 mg/m2 for 24 hours, once every 3 weeks) or TACE (epirubicin 50 mg, lobaplatin 50 mg, and lipiodol and polyvinyl alcohol particles). The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received ≥ 1 cycle of study treatment. RESULTS: Between October 1, 2016, and November 23, 2018, 315 patients were randomly assigned to FOLFOX-HAIC (n = 159) or TACE (n = 156). The median overall survival in the FOLFOX-HAIC group was 23.1 months (95% CI, 18.5 to 27.7) versus 16.1 months (95% CI, 14.3 to 17.9) in the TACE group (hazard ratio, 0.58; 95% CI, 0.45 to 0.75; P < .001). The FOLFOX-HAIC group showed a higher response rate than the TACE group (73 [46%] v 28 [18%]; P < .001) and a longer median progression-free survival (9.6 [95% CI, 7.4 to 11.9] v 5.4 months [95% CI, 3.8 to 7.0], P < .001). The incidence of serious adverse events was higher in the TACE group than in the FOLFOX-HAIC group (30% v 19%, P = .03). Two deaths in the FOLFOX-HAIC group and two in the TACE group were deemed to be treatment-related. CONCLUSION: FOLFOX-HAIC significantly improved overall survival over TACE in patients with unresectable large hepatocellular carcinoma.

2.
Hepatology ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536297

RESUMO

We appreciate the interest of Zhai and colleagues in our article recently published in Hepatology on the association between serum levels of total, free, and bioavailable 25-hydroxyvitamin D (25OHD) and hepatocellular carcinoma (HCC) survival(1) . They raised three important points, especially the last two, which allow us to further evaluate the predictive performance of bioavailable 25OHD for HCC prognosis.

3.
JAMA Netw Open ; 4(9): e2126992, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34570206

RESUMO

Importance: The long-term outcomes of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) are not determined. Objective: To report the long-term outcomes of TACE-RFA. Design, Setting, and Participants: This cohort study analyzed long-term follow-up data from a phase 3 randomized clinical trial of adults with early HCC conducted from October 2006 to June 2009. Participants were randomly assigned to the TACE-RFA group or the RFA group in a 1:1 ratio and followed up approximately 6 years after the trial was closed. Data analysis was performed March 2020. Exposure: In the TACE-RFA group, TACE was performed first, and RFA was done 2 weeks later. Main Outcomes and Measures: Overall survival (OS) and recurrence-free survival (RFS). Results: Of 189 patients who were included (mean [SD] age, 54.3 [12.0] years; 146 [77.2%] men), 94 and 95 patients were assigned to the TACE-RFA group and RFA group, respectively, with their baseline characteristics well matched. Three patients in each group were lost to follow-up. The 5-year and 7-year OS rates for the TACE-RFA group vs the RFA group were 52.0% and 36.4% vs 43.2% and 19.4%, respectively (hazard ratio [HR], 0.55; 95% CI, 0.39-0.78; P = .001). The 5-year and 7-year RFS rates for the TACE-RFA group vs the RFA group were 41.4% and 34.5% vs 27.4% and 18.1%, respectively (HR, 0.66; 95% CI, 0.49-0.89; P = .007). On subgroup analysis comparing patients who had tumors larger than 3 cm with those who had tumors 3 cm or smaller, the OS and RFS survival rates in the TACE-RFA group (HR, 3.20; 95% CI, 1.91-5.35, P < .001) were significantly better than those in the RFA group (HR, 2.03; 95% CI, 1.30-3.17; P = .002). Conclusions and Relevance: In this cohort study, combined RFA and TACE was associated with better survival than RFA alone on long-term follow-up. Patients with tumors 3 cm or smaller did not benefit as well as patients with tumors larger than 3 cm from the combined treatment.

4.
Eur J Cancer ; 155: 85-96, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34371445

RESUMO

AIM: The prediction model of postoperative survival for single large and huge hepatocellular carcinoma (SLH-HCC, diameter > 5.0 cm) without portal vein tumour thrombus has not been well established. This study aimed to develop novel nomograms to predict postoperative recurrence and survival of these patients. METHODS: Data from 2469 patients with SLH-HCC who underwent curative resection from January 2005 to December 2015 in China were retrospectively collected. Specifically, nomograms of recurrence-free survival (RFS) and overall survival (OS) using data from a training cohort were developed with the Cox regression model (n = 1012). The modes were verified in an internal validation cohort (n = 338) and an external cohort comprising four tertiary institutions (n = 1119). RESULTS: The nomograms of RFS and OS based on tumour clinicopathologic features (diameter, differentiation, microvascular invasion, α-fetoprotein), operative factors (preoperative transcatheter arterial chemoembolisation therapy, scope of liver resection and intraoperative blood transfusion), underlying liver function (albumin-bilirubin grade) and systemic inflammatory or immune status (neutrophil-to-lymphocyte ratio) achieved high C-indexes of 0.85 (95% confidence interval [CI], 0.79-0.91) and 0.86 (95% CI, 0.79-0.93) in the training cohort, respectively, which were significantly higher than those of the five conventional HCC staging systems (0.62-0.73 for RFS, 0.63-0.75 for OS). The nomograms were validated in the internal cohort (0.83 for RFS, 0.84 for OS) and external cohort (0.87 for RFS, 0.88 for OS) and had well-fitted calibration curves. Our nomograms accurately stratified patients with SLH-HCC into low-, intermediate- and high-risk groups of postsurgical recurrence and mortality. CONCLUSIONS: The two nomograms achieved optimal prediction for postsurgical recurrence and OS for patients with SLH-HCC after curative resection.

5.
Hepatology ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34435708

RESUMO

Androgen receptor (AR) has been reported to play an important role in the development and progression of man's prostate cancer. Hepatocellular carcinoma (HCC) is also male-dominant, but the role of AR in HCC remains poorly understood. Here we show that mTORC1 interacts with hepatic AR and phosphorylates it at S96 in response to nutrient and mitogenic stimuli in HCC cells. S96 phosphorylation promotes the stability, nuclear localization and transcriptional activity of AR, which enhances de novo lipogenesis and proliferation in hepatocytes and induces liver steatosis and hepatocarcinogenesis in mice independently and cooperatively with androgen. Furthermore, high ARS96 phosphorylation is observed in human liver steatotic and HCC tissues and is associated with overall survival and disease-free survival, which has been proven as an independent survival predictor for HCC patients. IN CONCLUSION: AR S96 phosphorylation by mTORC1drives liver steatosis and HCC development and progression independently and cooperatively with androgen, which not only explains why HCC is man-biased but also provides a target molecule for prevention and treatment of HCC and a potential survival predictor in HCC patients.

6.
J Hepatocell Carcinoma ; 8: 657-670, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34235104

RESUMO

Background: The importance of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) in hepatocellular carcinoma (HCC) has been studied extensively in Japan, where hepatitis C virus is the predominant aetiology of HCC. The clinical profiles of HCC regarding the state of AFP and DCP in a hepatitis B virus epidemic area have not been comprehensively investigated, and the value of these tumour markers in evaluating the response to treatment and the detection of recurrence has yet to be determined. Patients and Methods: A total of 4792 patients treated in our centre were continuously analysed regarding accessible AFP and DCP data pre- and posttreatment. Baseline characteristics were summarized, and comparisons of progression-free survival (PFS) and overall survival (OS) rates were made independently. The prognostic significance of each factor was tested with the Cox proportional hazards model. Patients who had AFP and DCP data pretreatment, pre- and posttreatment, and those who were continuously monitored more than twice were analysed separately. Results: A total of 2600 patients (53.4%) were positive for AFP and DCP; 362 (7.6%) and 1211 (25.3%) patients were AFP- or DCP-positive, respectively, and 619 patients (12.9%) were negative for both AFP and DCP. Patients in the AFP single-positive or double-negative groups had the best OS (P<0.001). Patients with less than 50% responses in AFP and DCP after treatments suffered from worse prognostic survival (P<0.001). In the multivariate analysis, elevated AFP and DCP were identified as independent prognostic factors of PFS and OS. In addition, different tumour markers were related to different clinical and pathological traits. Conclusion: The present study comprehensively explored the clinical value of classical tumour markers for HCC using the "point-to-line" method. Positivity of pretreatment AFP and DCP or less than 50% treatment response rates exhibited more aggressive HCC, resulting in poor PFS and OS in HCC patients.

7.
J Inflamm Res ; 14: 2483-2495, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34140796

RESUMO

Purpose: This study aimed to evaluate the prognostic value of the lymphocyte-C-reactive protein ratio (LCR) score, a novel inflammation-based score based on lymphocytes and C-reactive protein, in hepatocellular carcinoma (HCC) patients treated with curative intent. Patients and Methods: A total of 1158 HCC patients undergoing surgical resection or radiofrequency ablation with curative intent were recruited from 3 different centres and divided into a primary cohort (n=716) and a validation cohort (n=442). Univariate and multivariate analyses were performed to identify variables associated with overall survival (OS). The discriminatory accuracy of seven inflammation-based scores was compared by using the concordance index (C-index). Results: The LCR score differentiated HCC patients into two groups with distinct prognoses (1-, 3-, and 5-year OS rates and median OS: 92.9%, 81.9%, 73.3% and 99.2 months and 79.8%, 56.6%, 49.7% and 69.1 months; P<0.001). Multivariate analysis showed that LCR score, AFP, ALBI score, tumour size, and TNM stage were independently associated with OS. When patients were stratified according to different disease states, the LCR score could still differentiate HCC patients into two groups with distinct prognoses (all P<0.005). The LCR score demonstrated a markedly superior C-index of 0.621 compared with the other inflammation-based scores (0.503-0.590). These findings were supported by the validation cohort. Conclusion: The preoperative LCR score is a novel, stable, and clinically feasible prognostic marker for patients with HCC, independent of liver function, tumour characteristics, and treatment allocation and is superior to other inflammation-based scores in terms of its prognostic ability.

8.
Front Oncol ; 11: 619461, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055599

RESUMO

Purpose: Our previous study showed that hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin (FOLFOX) plus sorafenib provided a significant survival benefit over sorafenib for advanced hepatocellular carcinoma. However, it is unclear whether the survival benefit should be attributed to the synergism between HAIC and sorafenib or just HAIC alone. We aim to compare HAIC using FOLFOX plus sorafenib with HAIC alone in patients with advanced hepatocellular carcinoma. Materials and Methods: This was a retrospective study including 225 eligible patients treated with HAIC using FOLFOX (HAIC alone group, n=126, oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil bolus 400 mg/m² and 2400 mg/m² for 46 hours, every 3 weeks) alone or HAIC plus sorafenib (soraHAIC group, n=99, sorafenib 400 mg twice daily). Survival curves were calculated by the Kaplan-Meier method, and propensity-score matching was used to reduce bias. Results: The soraHAIC group showed a longer overall survival (12.9 [95% CI, 10.4-15.4] vs. 10.5 [95% CI, 9.5-11.5] months, HR=0.71 [95% CI, 0.53-0.96]; P=0.025), a better progression free survival (7.0 [95% CI, 5.3-8.8] vs. 5.3 [95% CI, 3.5-7.1] months, HR=0.76 [95% CI, 0.58-0.99]; P=0.046), and a higher disease control rate (RECIST 1.1: 74.8% vs. 61.1%, P=0.030) than the HAIC alone group. In multivariate analysis, soraHAIC was an independent favor factor for survival. In terms of the grade 3/4 adverse event, hand-foot skin reaction was more frequent in the soraHAIC group than the HAIC alone group. In the propensity-score matched cohorts (93 pairs), the overall survival, the progression free survival and disease control rates in the soraHAIC group were also better than those in the HAIC group (P<0.05). Conclusion: HAIC plus sorafenib may improve overall survival and progression free survival compared with HAIC alone as initial treatment for advanced hepatocellular carcinoma.

9.
Cancer Immunol Immunother ; 70(11): 3207-3216, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33813646

RESUMO

BACKGROUND: Programmed cell death protein-1 (PD-1) inhibitor is recommended to treat advanced hepatocellular carcinoma (HCC). However, the safety of PD-1 inhibitor in patients with high HBV-DNA load is unknown because of the potential risk of hepatitis B virus (HBV) reactivation. This study was to compare the HBV reactivation between patients with low HBV-DNA loads and high HBV-DNA loads undergoing antiviral prophylaxis and PD-1 inhibitor. METHODS: This was a retrospective study including consecutive hepatitis B surface antigen-positive HCC patients who received PD-1 inhibitor and concurrent antiviral prophylaxis for prevention of clinical hepatitis. Patients were divided into low HBV-DNA group (low group, ≤ 500 IU/ml) and high HBV-DNA group (high group, > 500 IU/ml) according to the baseline HBV-DNA level. The incidences of HBV reactivation, HBV-associated hepatitis, and PD-1 inhibitor disruption were compared between the two groups. RESULTS: Two hundred two eligible patients were included: 94 in the low group and 108 in the high group. Seven patients (5 in the low group and 2 in the high group) developed HBV reactivation, and all recovered from HBV reactivation and HBV-associated hepatitis. The incidence of HBV reactivation in the two groups was low (5.3% vs 1.9%, P = 0.34). There was also no difference in the incidence of HBV-associated hepatitis (P = 0.56), or PD-1 inhibitor disruption (P = 0.82). The multivariable analysis showed PD-1 inhibitor with hepatic arterial infusion chemotherapy was the only significant risk factor for HBV reactivation (P = 0.04) and hepatitis (P = 0.002). CONCLUSION: With concurrent antiviral prophylaxis, HBV-DNA load higher than 500 IU/ml should not be a contraindication for PD-1 inhibitor.


Assuntos
Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Hepáticas/virologia , Ativação Viral/efeitos dos fármacos , Adulto , Idoso , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Feminino , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/fisiologia , Humanos , Incidência , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral
10.
Acta Pharmacol Sin ; 42(9): 1486-1497, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33893396

RESUMO

Non-small cell lung cancer (NSCLC) is characterized by a high incidence of metastasis and poor survival. As epithelial-mesenchymal transition (EMT) is well recognized as a major factor initiating tumor metastasis, developing EMT inhibitor could be a feasible treatment for metastatic NSCLC. Recent studies show that triptolide isolated from Tripterygium wilfordii Hook F attenuated the migration and invasion of breast cancer, colon carcinoma, and ovarian cancer cells, and EMT played important roles in this process. In the present study we investigated the effect of triptolide on the migration and invasion of NSCLC cell lines. We showed that triptolide (0.5, 1.0, 2.0 nM) concentration-dependently inhibited the migration and invasion of NCI-H1299 cells. Triptolide treatment concentration-dependently suppressed EMT in NCI-H1299 cells, evidenced by significantly elevated E-cadherin expression and reduced expression of ZEB1, vimentin, and slug. Furthermore, triptolide treatment suppressed ß-catenin expression in NCI-H1299 and NCI-H460 cells, overexpression of ß-catenin antagonized triptolide-caused inhibition on EMT, whereas knockout of ß-catenin enhanced the inhibitory effect of triptolide on EMT. Administration of triptolide (0.75, 1.5 mg/kg per day, ip, every 2 days) for 18 days in NCI-H1299 xenograft mice dose-dependently suppressed the tumor growth, restrained EMT, and decreased lung metastasis, as evidence by significantly decreased expression of mesenchymal markers, increased expression of epithelial markers as well as reduced number of pulmonary lung metastatic foci. These results demonstrate that triptolide suppresses NSCLC metastasis by targeting EMT via reducing ß-catenin expression. Our study implies that triptolide may be developed as a potential agent for the therapy of NSCLC metastasis.

11.
J Hepatocell Carcinoma ; 8: 167-176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791252

RESUMO

Background: Hepatic artery infusion chemotherapy (HAIC) and anti-programmed cell death protein-1 (PD-1) immunotherapy have shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC), respectively. However, the combination of the two treatments has not been reported. In this study, we compared the efficacy of HAIC combined with anti-PD-1 immunotherapy (HAICAP) and HAIC in patients with advanced HCC. Methods: Between November 2018 and December 2019, advanced HCC patients that were treated with either HAICAP or HAIC were retrospectively recruited and reviewed for eligibility. Efficacy was evaluated according to tumor response and survival. Results: As a result, 229 patients were included in this study. Patients were divided into HAICAP group (n = 81) and HAIC group (n = 148) accordingly. The follow-up time ranged from 1.0 to 21.6 months, with a median of 11.0 months. The median overall survival was 18.0 months in the HAICAP group and 14.6 months in the HAIC group (p = 0.018; HR = 0.62; 95% CI 0.34-0.91). The median progression-free survival was 10.0 months in the HAICAP group and 5.6 months in the HAIC group (p = 0.006; HR = 0.65; 95% CI 0.43-0.87). The disease control rate in overall response (83% vs 66%; p = 0.006) and intrahepatic response (85% vs 74%, respectively; p = 0.045) were higher in the HAICAP group than in the HAIC group. Conclusion: In comparison to HAIC, HAICAP was associated with a better treatment response and survival benefits for patients with advanced HCC.

12.
Ther Adv Med Oncol ; 13: 17588359211002720, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854567

RESUMO

Background: Lenvatinib is the first-line treatment for advanced hepatocellular carcinoma, but prognosis is still unsatisfactory. Recently, hepatic arterial infusion chemotherapy (HAIC), and immune checkpoint inhibitors showed promising results for advanced hepatocellular carcinoma. Considering different anti-malignancy mechanisms, combining these three treatments may improve outcomes. This study aimed to compare the efficacy and safety of lenvatinib, toripalimab, plus HAIC versus lenvatinib for advanced hepatocellular carcinoma. Methods: This was a retrospective study including patients treated with lenvatinib [8 mg (⩽60 kg) or 12 mg (>60 kg) once daily] or lenvatinib, toripalimab plus HAIC [LeToHAIC group, lenvatinib 0-1 week prior to initial HAIC, 240 mg toripalimab 0-1 day prior to every HAIC cycle, and HAIC with FOLFOX regimen (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 46 h, every 3 weeks)]. Progression-free survival, overall survival, objective response rate, and treatment-related adverse events were compared. Results: From February 2019 to August 2019, 157 patients were included in this study: 71 in the LeToHAIC group and 86 in the lenvatinib group. The LeToHAIC group showed longer progression-free survival (11.1 versus 5.1 months, p < 0.001), longer overall survival (not reached versus 11 months, p < 0.001), and a higher objective response rate (RECIST: 59.2% versus 9.3%, p < 0.001; modified RECIST: 67.6% versus 16.3%, p < 0.001) than the lenvatinib group. In addition, 14.1% and 21.1% of patients in the LeToHAIC group achieved complete response of all lesions and complete response of the intrahepatic target lesions per modified RECIST criteria, respectively. Grade 3/4 treatment-related adverse events that were more frequent in the LeToHAIC group than in the lenvatinib group included neutropenia (8.5% versus 1.2%), thrombocytopenia (5.6% versus 0), and nausea (5.6% versus 0). Conclusions: Lenvatinib, toripalimab, plus HAIC had acceptable toxic effects and might improve survival compared with lenvatinib alone in advanced hepatocellular carcinoma.

13.
J Clin Lab Anal ; 35(6): e23776, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33792998

RESUMO

BACKGROUND: Nowadays, hand, foot, and mouth disease (HFMD) has a significant negative impact on children's health, especially in the Asia-Pacific region. Loop-mediated isothermal amplification assay (LAMP) is a highly efficient and convenient novel tool. However, its diagnostic accuracy for HFMD is still not clear. Therefore, we conducted a meta-analysis in order to evaluate the potential of LAMP assay for the diagnosis of HFMD, in which the reference standard was polymerase chain reaction (PCR). METHODS: A protocol was predetermined (CRD42020212882) in PROSPERO. We retrieved seven databases including PubMed for relevant studies published before October 2020. Articles were included if they compared the diagnostic efficiency of LAMP with PCR for HFMD through detecting clinical samples which was more than 15. Statistical analysis was performed by STATA 15.1 software. Risk of bias and applicability were assessed using Quality Assessment of Diagnostic Accuracy Studies. No funding was used for the study. RESULTS: A total of 18 retrospective studies including 2495 samples from China were finally included. Reference standards of them included RT-PCR and non-RT-PCR. The merged sensitivity and specificity with 95% confidence interval (95% CI) were 1.00 (0.97-1.00) and 0.97 (0.88-0.99), respectively. The pooled PLR, NLR, and DOR with 95% CI were 11.17 (5.91-21.11), 0.05 (0.03-0.09), and 538.12 (183.17-1580.83), respectively. The AUC of SROC was 1.00 (95% CI: 0.99-1.00). CONCLUSION: In conclusion, our research revealed high sensitivity and specificity of LAMP in diagnosing HFMD. However, more high-quality research is required to prove this conclusion.

14.
Int J Cancer ; 149(1): 127-138, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33586134

RESUMO

The population of patients with huge hepatocellular carcinoma (H-HCC diameter > 10.0 cm) is an odd group that is not well adjudicated in the current staging systems, whose prognosis after curative resection varies. We aimed to develop novel models to predict the long-term outcomes of patients with H-HCC without portal vein tumor thrombus after hepatectomy. There were 1076 H-HCC patients enrolled who underwent curative liver resection in five institutions in China. In total, 670 patients were recruited from our center and randomly divided into the training cohort (n = 502) and internal validation (n = 168) cohorts. Additionally, 406 patients selected from other four centers as the external validation cohort. Novel models were constructed based on independent preoperative and postoperative predictors of postsurgical recurrence (PSR) and postsurgical mortality (PSM) determined in multivariable cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell's concordance index (C index) and calibration curve and compared with five conventional HCC staging systems. PSR model and PSM model were constructed based on tumor number, microscopic vascular invasion, tumor differentiation, preoperative alpha-fetoprotein level, albumin-bilirubin grade, liver segment invasion, neutrophil-to-lymphocyte ratio or platelet-to-neutrophil ratio, and surgical margin or intraoperative blood transfusion. The C-indexes were 0.84 (95% CI, 0.78-0.90) and 0.85 (95% CI, 0.78-0.91) for the PSR and PSM models, respectively, which were substantially higher than those of the five conventional HCC staging systems (0.63-0.75 for PSR; 0.66-0.77 for PSM). The two novel models achieved more accurate prognostic predictions of PSR and PSM for H-HCC patients after curative liver resection.


Assuntos
Carcinoma Hepatocelular/patologia , Hepatectomia/mortalidade , Neoplasias Hepáticas/patologia , Modelos Estatísticos , Recidiva Local de Neoplasia/patologia , Nomogramas , Carcinoma Hepatocelular/cirurgia , China , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
15.
Front Oncol ; 10: 1639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194569

RESUMO

Background: Both stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) are effective local treatments for hepatocellular carcinoma (HCC), but whether RFA is superior to SBRT is still controversial. Therefore, we performed a meta-analysis to compare the treatment outcomes of SBRT with RFA as curable or bridge intention. Methods: We searched online databases for studies that compared treatment outcomes for SBRT and RFA. Eligibility criteria included evaluation of local control, overall survival (OS), transplant rate, and post-transplant pathological necrosis. Results: As no randomized clinical trials met the criteria, 10 retrospective studies with a total of 2,732 patients were included. Two studies were in favor of SBRT in local control, two studies preferred RFA in OS, and others reported comparable outcomes for both. SBRT demonstrated significantly higher 1- and 3-year local control than RFA [odds ratio (OR) 0.42, 95% CI 0.24-0.74, P = 0.003; and OR 0.54, 95% CI 0.37-0.80, P = 0.002, respectively]. However, SBRT reported significantly shorter 1- and 2-year OS (OR 1.52, 95% CI 1.21-1.90, P = 0.0003; and OR 1.66, 95% CI 1.38-2.01, P < 0.00001, respectively). As bridge treatment, no significant difference was shown in transplant rate and post-transplant pathological necrosis rate (OR 0.57, 95% CI 0.32-1.03, P = 0.060; and OR 0.49, 95% CI 0.13-1.82, P = 0.290, respectively). Conclusions: This study demonstrates SBRT is able to complete a better local control for HCC than RFA, though the OS is inferior to RFA because of tumor burden or liver profiles of the enrolled studies. Well-designed, randomized, multicenter trials will be required to further investigate the conclusion.

16.
Cancer Commun (Lond) ; 40(8): 355-369, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32609436

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem and a primary cause of cancer-related death worldwide. Although great advances have achieved recently by large-scale high-throughput analysis, the precise molecular mechanism underlying HCC progression remains to be clearly elucidated. We investigated the relationship between Tescalcin (TESC), a candidate oncogene, and clinicopathological features of HCC patients and explored the role of TECS in HCC development. METHODS: To identify new genes involved in HCC development, we analyzed The Cancer Genome Atlas liver cancer database, and TESC was selected for further investigation. HCC tissue microarray analysis for TESC and its association with clinicopathological features were performed to investigate its clinical significance. TESC was knocked down by using short-hairpin RNAs. Cell proliferation was analyzed by WST-1 assay and cell counting. Cell apoptosis was tested by fluorescence-activated cell sorting. A subcutaneous xenograft tumor model in nude mice was established to determine the in vivo function of TESC. Affymetrix microarray was used to identify its molecular mechanism. RESULTS: TESC was significantly increased in HCC tissues compared with the adjacent normal liver tissues. High expression of TESC was detected in 61 of 172 HCC patients by tissue microarray. Large tumor (> 5 cm) and elevated total bilirubin were associated with high TESC expression (both P < 0.050). In multivariate analysis, TESC was identified as an independent prognostic factor for short overall survival of HCC patients. TESC knockdown impaired HCC cell growth in vitro and in vivo. TESC knockdown significantly increased cell apoptosis in HCC cell lines. Furthermore, Affymetrix microarray analysis revealed that TESC knockdown inhibited tumor proliferation-related pathways while activated cell death-related pathways. CONCLUSION: TESC was identified as an independent prognostic factor for short overall survival of HCC patients, and was critical for HCC cell proliferation and survival.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Animais , Apoptose , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Proliferação de Células , Feminino , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Prognóstico
17.
Hepatol Res ; 50(10): 1164-1175, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32691459

RESUMO

AIM: Adherence to dietary recommendations has been linked to a reduced risk of developing hepatocellular carcinoma (HCC) and dying of chronic liver disease. However, its role in the prognosis of HCC is still unclear. We prospectively investigated the association of two dietary quality indices, the Chinese Healthy Eating Index (CHEI) and the Healthy Eating Index-2015 (HEI-2015), with all-cause and HCC-specific mortality in a large prospective cohort of HCC survivors. METHODS: We included 887 patients with newly diagnosed, previously untreated HCC enrolled in the Guangdong Liver Cancer Cohort (GLCC) between September 2013 and April 2017 in the analysis. CHEI and HEI-2015 scores were calculated based on the dietary intake in the year before diagnosis of HCC. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for each index. RESULTS: During a median follow-up of 797 days, 389 deaths were identified, including 347 from HCC. Higher CHEI scores, reflecting favorable adherence to the 2016 Dietary Guidelines for Chinese, were associated with a lower risk of all-cause mortality (T3 vs. T1 : HR = 0.75, 95% CI: 0.58-0.98) and HCC-specific mortality (T3 vs. T1 : HR = 0.74, 95% CI: 0.56-0.98). Non-significant, inverse associations of HEI-2015 score with all-cause mortality (T3 vs. T1 : HR = 0.86, 95% CI: 0.67-1.11) and HCC-specific mortality (T3 vs. T1 : HR = 0.93, 95% CI: 0.71-1.21) were suggested. CONCLUSIONS: Our findings suggest that better adherence to the 2016 Dietary Guidelines for Chinese may reduce the risk of all-cause and HCC-specific mortality in patients with HCC.

18.
Theranostics ; 10(17): 7527-7544, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32685003

RESUMO

Emerging evidence suggests that long non-coding RNAs (lncRNA) play critical roles in the development and progression of diverse cancers including hepatocellular carcinoma (HCC), but the underlying molecular mechanisms of lncRNAs that are involved in hepatocarcinogenesis have not been fully explored. Methods: In this study, we profiled lncRNA expression in 127 pairs of HCC and nontumor liver tissues (a Discovery Cohort) using a custom microarray. The expression and clinical significance of lncCSMD1-1 were then validated with qRT-PCR and COX regression analysis in a Validation Cohort (n=260) and two External Validation Cohorts (n=92 and n=124, respectively). In vitro and in vivo assays were performed to explore the biological effects of lncCSMD1-1 on HCC cells. The interaction of lncCSMD1-1 with MYC was identified by RNA pull-down and RNA immunoprecipitation. The role of LncCSMD1-1 in the degradation of MYC protein was also investigated. Results: With microarray, we identified a highly upregulated lncRNA, lncCSMD1-1, which was associated with tumor progression and poor prognosis in the Discovery Cohort, and validated in another 3 HCC cohorts. Consistently, ectopic expression of lncCSMD1-1 notably promotes cell proliferation, migration, invasion, tumor growth and metastasis of HCC cells in in vitro and in vivo experiments. Gene expression profiling on HCC cells and gene sets enrichment analysis indicated that the MYC target gene set was significantly enriched in HCC cells overexpressing lncCSMD1-1, and lncCSMD1-1 was found to directly bind to MYC protein in the nucleus of HCC cells, which resulted in the elevation of MYC protein. Mechanistically, lncCSMD1-1 interacted with MYC protein to block its ubiquitin-proteasome degradation pathway, leading to activation of its downstream target genes. Conclusion: lncCSMD1-1 is upregulated in HCC and promotes progression of HCC by activating the MYC signaling pathway. These results provide the evidence that lncCSMD1-1 may serve as a novel prognostic marker and potential therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Recidiva Local de Neoplasia/epidemiologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/metabolismo , Carcinogênese/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/secundário , Carcinoma Hepatocelular/cirurgia , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Hepatectomia , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Prognóstico , Proteólise , Transdução de Sinais/genética , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J Clin Invest ; 130(9): 4679-4693, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497024

RESUMO

BACKGROUNDDespite an increasing appreciation of the roles that myeloid cells play in tumor progression and therapy, challenges remain in interpreting the tumor-associated myeloid response balance and its translational value. We aimed to construct a simple and reliable myeloid signature for hepatocellular carcinoma (HCC).METHODSUsing in situ immunohistochemistry, we assessed the distribution of major myeloid subtypes in both peri- and intratumoral regions of HCC. A 2-feature-based, myeloid-specific prognostic signature, named the myeloid response score (MRS), was constructed using an L1-penalized Cox regression model based on data from a training subset (n = 244), a test subset (n = 244), and an independent internal (n = 341) and 2 external (n = 94; n = 254) cohorts.RESULTSThe MRS and the MRS-based nomograms displayed remarkable discriminatory power, accuracy, and clinical usefulness for predicting recurrence and patient survival, superior to current staging algorithms. Moreover, an increase in MRS was associated with a shift in the myeloid response balance from antitumor to protumor activities, accompanied by enhanced CD8+ T cell exhaustion patterns. Additionally, we provide evidence that the MRS was associated with the efficacy of sorafenib treatment for recurrent HCC.CONCLUSIONWe identified and validated a simple myeloid signature for HCC that showed remarkable prognostic potential and may serve as a basis for the stratification of HCC immune subtypes.FUNDINGThis work was supported by the National Science and Technology Major Project of China, the National Natural Science Foundation of China, the Science and Information Technology of Guangzhou, the Fundamental Research Funds for the Central Universities, the Guangdong Basic and Applied Basic Research Foundation, and the China Postdoctoral Science Foundation.


Assuntos
Biomarcadores Tumorais/imunologia , Carcinoma Hepatocelular , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias Hepáticas , Células Mieloides , Sorafenibe/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Células Mieloides/imunologia , Células Mieloides/patologia , Taxa de Sobrevida
20.
Aging (Albany NY) ; 12(12): 12187-12205, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32544882

RESUMO

Recent studies demonstrate that immune checkpoint inhibitor (ICI) therapy has achieved success in many types of advanced cancers including advanced hepatocellular carcinoma (HCC). However, ICI therapy is beneficial in only some HCC patients, suggesting that immune-responses are highly variable in HCCs. Therefore, understanding the immune status in HCC microenvironment will facilitate ICI immunotherapy and guide patient selection for the therapy. In this study, we first analyzed the expression profile of immune-modulating genes and their relationship with survival of HCC patients using the data downloaded from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC) database, and found that the higher expressions of CD276 (B7-H3) and CD47 were significantly associated with poor survival. Then we identified 4 immune subtypes of HCCs with different survivals by using the combination expression of B7-H3 (or CD47) and CD8. Patients with B7-H3low/CD8high or CD47low/CD8high have the best survival while ones with B7-H3high/CD8low or CD47high/CD8low have the worst survival. The 4 immune subtypes were validated in another 72 HCC patients obtained from South China. In conclusion, our findings suggest that HCC patient prognosis is associated with immunophenotypes by T cell infiltration (CD8 expression) and the expression of the adaptive immune resistance gene (B7-H3 or CD47), and this immune classification system will facilitate HCC patient selection for ICI immunotherapy.


Assuntos
Antígenos B7/metabolismo , Antígeno CD47/metabolismo , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/imunologia , Linfócitos T/metabolismo , Adulto , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , China/epidemiologia , Conjuntos de Dados como Assunto , Progressão da Doença , Feminino , Hepatectomia , Humanos , Imunoterapia , Estimativa de Kaplan-Meier , Fígado/imunologia , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Prognóstico , RNA-Seq , Estudos Retrospectivos , Linfócitos T/imunologia , Microambiente Tumoral/imunologia
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