Risk of Death due to Hepatocellular Carcinoma among Smokers and Ex-smokers. Univariate Analysis of JACC Study Data

Background. Epigenetic dysregulation via alteration of DNA methylation often occurs during the development and progression of cancer, including hepatocellular carcinoma (HCC). In the past, many patterns of single-gene DNA methylation have been extensively explored in the context of HCC prognosis prediction. However, the combined model of a mixture of CpGs has rarely been evaluated. In the present study, we aimed to develop and validate a CpG-based signature model for HCC patient prognosis. Methods. Data from methylation profiling of GSE73003, GSE37988, and GSE57958 from the Gene Expression Omnibus (GEO) database and 371 HCC patients from the Cancer Genome Atlas (TCGA) were downloaded. The 371 HCC patients were randomly divided into a development cohort (N = 263) and a validation cohort (N = 108). Two algorithms, least absolute shrinkage and selection operator (LASSO) and robust likelihood-based survival analysis, were used to select the most significant CpGs associated with overall survival (OS) time and were used to develop and validate a methylation-based signature (MSH) for HCC patient prognosis. In addition, the prognostic efficacy of the MSH was compared with that of AJCC TNM classification and other CpG-based MSHs from TCGA. Finally, a nomogram incorporating the MSH and clinicopathologic factors was also developed. Results. Fourteen differential CpGs associated with OS were identified in HCC patients. The MSH, based on these 14 differential CpGs, could effectively divide HCC patients into two distinct subgroups with high risk or low risk of death (P<0.0001) in the development cohort (26.35 vs 83.18 months, HR = 3.83, 95% CI: 2.56–5.90, P<0.0001) and in the validation cohort (40.37 vs 107.03 months, HR = 2.23, 95% CI: 1.22–4.17, P=0.01). Univariate analysis showed that the MSH was significantly associated with OS, and the multivariate analysis also showed that the MSH was an independent prognostic factor for the OS of HCC patients in the two cohorts. In addition, stratified survival analysis indicated that the MSH still exhibited good prognostic value in different subgroups classified by AFP, cirrhosis, Child-Pugh A, tumor histologic grade, and AJCC stage. Moreover, time-dependent ROC analysis showed better performance of the MSH in predicting 3-year and 5-year survival of HCC patients than of AJCC stage and other CpG-based signatures from TCGA. The MSH-based nomogram also performed well in predicting 1-year, 3-year, and 5-year OS (C-index: 0.709). Conclusion. The 14-CpG-based signature is significantly associated with OS and may be used as a novel prognostic biomarker for HCC patients.

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The Prognostic Correlation of Heart Rate Variability at Diagnosis with Survival of Patients with Hepatocellular Carcinoma

Diagnostics ◽

10.3390/diagnostics11050890 ◽

2021 ◽

Vol 11 (5) ◽

pp. 890

Author(s):

Ana-Maria Ciurea ◽

Dan Ionuț Gheonea ◽

Michael Schenker ◽

Alina Maria Mehedințeanu ◽

Georgică Costinel Târtea ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Heart Rate ◽

Heart Rate Variability ◽

Tumor Size ◽

Cox Regression ◽

Univariate Analysis ◽

Early Therapy ◽

Reactive Protein ◽

Risk Of Death ◽

Noninvasive Biomarker

Background: Heart rate variability (HRV) indices have been shown to be associated with prognosis in various types of cancer. This study aims to assess the ability of these indices to predict survival in hepatocellular carcinoma (HCC) patients after diagnosis. Methods: We retrospectively collected data from 231 patients diagnosed with HCC between January 2014 and March 2018. The baseline clinical-pathological variables and HRV indices (extracted from Holter electrocardiogram recordings) were analyzed. Results: Univariate and multivariate analyses were performed to identify the predictive value of the above factors for overall survival (OS). The univariate analysis revealed that an age > 60 years, hepatitis C, portal vein involvement (thrombosis), a tumor size > 5 cm, alpha-fetoprotein (AFP) > 400 ng/mL, serum albumin, and C-reactive protein (CRP) were risk factors for poor OS. Multivariable Cox regression analyses identified that a tumor size > 5 cm and AFP > 400 ng/mL predict poorer outcomes in HCC patients. It should be mentioned that, in both the univariate analysis and in the multivariate analysis, between HRV indices, SDNN (standard deviation of all normal-to-normal (NN) intervals) < 110 ms was an independent risk factor for OS with an HR of 3.646 (95% CI 2.143 to 6.205). Conclusion: This study demonstrates that HRV indices identify HCC patients at high risk of death and suggests that such monitoring might guide the need for early therapy in these types of patients, as well as the fact that HRV can be a potential noninvasive biomarker for HCC prognosis.

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Serum lnc34a is a potential prediction biomarker for bone metastasis in hepatocellular carcinoma patients

BMC Cancer ◽

10.1186/s12885-021-07808-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Li Zhang ◽

Hao Niu ◽

Ping Yang ◽

Jie Ma ◽

Bao-Ying Yuan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Bone Metastasis ◽

Univariate Analysis ◽

High Serum ◽

Chain Reaction ◽

Serum Samples ◽

Early Screening ◽

Expression Levels ◽

Node Metastasis ◽

Polymerase Chain

Abstract Background Early screening and intervention therapies are crucial to improve the prognosis of hepatocellular carcinoma (HCC) patients with bone metastasis. We aimed to identify serum lncRNA as a prediction biomarker in HCC bone metastasis. Methods The expression levels of lnc34a in serum samples from 157 HCC patients were detected by quantitative real-time polymerase chain reaction (PCR). Univariate analysis and multivariate analysis were performed to determine statistically significant variables. Results Expression levels of lnc34a in serum from HCC patients with bone metastasis were significantly higher than those without bone metastasis. The high expressions of lnc34a, vascular invasion and Barcelona Clinic Liver Cancer (BCLC) stage were associated with bone metastasis by analysis. Moreover, lnc34a expression was specifically associated with bone metastasis rather than lung or lymph node metastasis in HCC. Conclusions High serum lnc34a expression was a independent risk factor for developing bone metastasis in HCC.

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Anaemia: A risk factor for death and adverse outcomes following surgery for acute lower limb ischaemia

Vascular ◽

10.1177/17085381211026167 ◽

2021 ◽

pp. 170853812110261

Author(s):

Daniel Perren ◽

Lauren Shelmerdine ◽

Luke Boylan ◽

Craig Nesbitt ◽

James Prentis ◽

...

Keyword(s):

Risk Factor ◽

Cox Model ◽

Univariate Analysis ◽

Adverse Outcomes ◽

Limb Ischaemia ◽

Risk Of Death ◽

Kaplan Meier ◽

Acute Limb Ischaemia ◽

Impact On Survival ◽

Poor Outcomes

Introduction Acute limb ischaemia (ALI) forms a significant part of the vascular surgery workload and carries with it high rates of morbidity and mortality. Anaemia is also common amongst vascular surgical patients and has been linked with poor outcomes in some subgroups. We aimed to assess the frequency of anaemia in patients with ALI and its impact on survival and complications following revascularisation to help direct future efforts to optimise outcomes in this patient group. Methods A retrospective analysis of prospectively collected departmental data on patients undergoing surgical intervention for ALI between 2014 and 2018 was performed. Anaemia was defined as a pre-operative haemoglobin (Hb) of <120 g/L for women and <130 g/L for men. The primary outcome was overall survival, assessed with the Kaplan–Meier estimator, with application of Cox proportional hazard modelling to adjust for confounding covariates. Results There were 158 patients who underwent treatment for ALI: 89 (56.3%) of these were non-anaemic with a mean Hb of 146 (SD = 18.4), and 69 (43.7%) were anaemic with a mean Hb of 106 (SD = 13.4). Anaemic patients had a significantly higher risk of death than their non-anaemic counterparts on univariate analysis (HR = 2.11, 95% CIs, 1.28–3.5, p = 0.0036). There was ongoing divergence in survival up to around 6 months between anaemic and non-anaemic groups. Under the Cox model, anaemia was similarly significant as a predictor of death (HR = 2.15, 95% CIs, 1.17–3.95, p = 0.013), accounting for recorded comorbidities, medication use and blood transfusion. Conclusions Anaemia is a significant and independent risk factor for death following revascularisation for ALI and can be potentially be modified. Vascular surgical centres should ensure they have robust pathways in place to identify and consider treating anaemia. There is scope for further work to assess how to best optimise a patient’s levels of circulating haemoglobin.

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

Diagnostics ◽

10.3390/diagnostics11010122 ◽

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.

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ATRT-26. META-ANALYSIS OF TREATMENT MODALITIES IN METASTATIC ATYPICAL TERATOID/RHABDOID TUMORS IN CHILDREN

Neuro-Oncology ◽

10.1093/neuonc/noaa222.025 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii281-iii281

Author(s):

Reena M Underiner ◽

Mostafa Eltobgy ◽

Joseph R Stanek ◽

Jonathan L Finlay ◽

Mohamed S AbdelBaki

Keyword(s):

Surgical Resection ◽

Meta Analysis ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Substantial Effect ◽

Treatment Modalities ◽

Risk Of Death ◽

Atypical Teratoid ◽

Atypical Teratoid Rhabdoid Tumors ◽

Rhabdoid Tumors

Abstract BACKGROUND Metastatic atypical teratoid/rhabdoid tumors (AT/RT) are aggressive central nervous system tumors that present during infancy and are associated with dismal outcomes. Patients receive multimodal treatment including surgical resection, systemic chemotherapy and one or more of intrathecal chemotherapy (IT), marrow-ablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) and radiation therapy (XRT). While data regarding treatment modalities for AT/RT patients exist, no comprehensive data have been published regarding the metastatic patient population. METHODS We performed a meta-analysis of 1,578 articles published through September 2018, including 44 studies with a total of 123 subjects. Additionally, seven patients were incorporated through chart review of patients treated at Nationwide Children’s Hospital. RESULTS Analysis of 130 patients revealed a 3-year overall survival (OS) of 25%. Age at diagnosis had a significant impact on survival (p=0.0355); 3-year OS for infants < 18 months was 21%; 18–36 months was 26%; and > 36 months was 36%. Location of the primary tumor, metastatic stage and extent of surgical resection did not have significant impact on OS. On univariate analysis, XRT (p<0.0001), IT (p=0.01) and AuHCR (p<0.0001) were found to significantly improve survival. The most substantial effect was noted in patients who received AuHCR (3-year OS of 60% versus 9% in those who did not). On multivariable analysis XRT (p=0.0006), IT (p=0.0124) and AuHCR (p<0.0001) were independently associated with reduced risk of death.

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Combined proteomic/transcriptomic signature of recurrence post-liver transplantation for hepatocellular carcinoma beyond Milan

Clinical Proteomics ◽

10.1186/s12014-021-09333-x ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Mamatha Bhat ◽

Sergi Clotet-Freixas ◽

Cristina Baciu ◽

Elisa Pasini ◽

Ahmed Hammad ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Protein Expression ◽

Univariate Analysis ◽

Milan Criteria ◽

Post Transplant ◽

Gene And Protein Expression ◽

Galectin 3 ◽

Transcriptomic Signature ◽

Hcc Recurrence

Abstract Background and aims Liver transplantation (LT) can be offered to patients with Hepatocellular carcinoma (HCC) beyond Milan criteria. However, there are currently limited molecular markers on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to derive a combined proteomic/transcriptomic signature on HCC explant predictive of recurrence post-transplant using unbiased, high-throughput approaches. Methods Patients who received a LT for HCC beyond Milan criteria in the context of hepatitis B cirrhosis were identified. Tumor explants from patients with post-transplant HCC recurrence (N = 7) versus those without recurrence (N = 4) were analyzed by mass spectrometry and gene expression array. Univariate analysis was used to generate a combined proteomic/transcriptomic signature linked to recurrence. Significantly predictive genes and proteins were verified and internally validated by immunoblotting and immunohistochemistry. Results Seventy-nine proteins and 636 genes were significantly differentially expressed in HCC tumors with subsequent recurrence (p < 0.05). Univariate survival analysis identified Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) gene (HR = 0.084, 95%CI 0.01–0.68, p = 0.0152), ALDH1A1 protein (HR = 0.039, 95%CI 0.16–0.91, p = 0.03), Galectin 3 Binding Protein (LGALS3BP) gene (HR = 7.14, 95%CI 1.20–432.96, p = 0.03), LGALS3BP protein (HR = 2.6, 95%CI 1.1–6.1, p = 0.036), Galectin 3 (LGALS3) gene (HR = 2.89, 95%CI 1.01–8.3, p = 0.049) and LGALS3 protein (HR = 2.6, 95%CI 1.2–5.5, p = 0.015) as key dysregulated analytes in recurrent HCC. In concordance with our proteome findings, HCC recurrence was linked to decreased ALDH1A1 and increased LGALS3 protein expression by Western Blot. LGALS3BP protein expression was validated in 29 independent HCC samples. Conclusions Significantly increased LGALS3 and LGALS3BP gene and protein expression on explant were associated with post-transplant recurrence, whereas increased ALDH1A1 was associated with absence of recurrence in patients transplanted for HCC beyond Milan criteria. This combined proteomic/transcriptomic signature could help in predicting HCC recurrence risk and guide post-transplant surveillance.

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