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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Currently, recent risk stratification has only focused on liver function and tumor characteristics. Thus, the purpose of this study was to develop a prognostic model based on genes involved in aerobic respiration. Matched tumor and normal tissues from TCGA and ICGC cohorts were analyzed to identify 15 overlapping differential expressed genes. Cox univariate analysis of the 15 genes in the TCGA cohort revealed they were all associated with disease-specific survival (DSS) in HCC patients. Using LASSO estimation and the optimal value for penalization coefficient lambda 12 genes were selected for the prognostic model, and then HCC patients in the TCGA cohort were dichotomized into low-risk and high-risk groups. Univariate and multivariate Cox analysis demonstrated patients in low-risk group had better survival. Validation of the risk score model with the ICGC cohort produces results consistent with those of the TCGA cohort. In conclusion, this study developed and validated a prognostic model of HCC through a comprehensive analysis of genes involved in aerobic respiration. This model may help develop personalized treatments for patients with HCC.
Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/genética , Respiração/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Perfilação da Expressão Gênica/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Prognóstico , Fatores de RiscoRESUMO
Progressive liver fibrosis may result in cirrhosis, portal hypertension and increased risk of hepatocellular carcinoma. We performed a meta-analysis to compare liver fibrosis staging in chronic liver disease patients using 2-D shear wave elastography (2-D SWE) and point shear wave elastography (pSWE). The PubMed, Web of Science and Cochrane Library databases were searched until May 31, 2020 for studies evaluating the diagnostic performance of 2-D SWE and pSWE in assessing liver fibrosis. Pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratios and area under receiver operating characteristic curve were estimated using the bivariate random effects model. As a result, 71 studies with 11,345 patients were included in the analysis. The pooled sensitivities of 2-D SWE and pSWE significantly differed for the detection of significant fibrosis (F ≥ 2; 0.84 vs. 0.76, p < 0.001) and advanced fibrosis (F ≥ 3; 0.90 vs. 0.83, pâ¯=â¯0.003), but not for detection of cirrhosis (Fâ¯=â¯4; 0.89 vs. 0.85, pâ¯=â¯0.090). The pooled specificities of 2-D SWE and pSWE did not significantly differ for detection of F ≥ 2 (0.81 vs. 0.79, pâ¯=â¯0.753), F ≥ 3 (0.87 vs. 0.83, pâ¯=â¯0.163) or Fâ¯=â¯4 (0.87 vs. 0.84, pâ¯=â¯0.294). Both 2-D SWE and pSWE have high sensitivity and specificity for detecting each stage of liver fibrosis. Two-dimensional SWE has higher sensitivity than pSWE for detection of significant fibrosis and advanced fibrosis.
Assuntos
Técnicas de Imagem por Elasticidade , Cirrose Hepática/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/patologia , Sensibilidade e EspecificidadeRESUMO
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide despite the availability of diverse treatment strategies. Much research progress has been made regarding immunotherapy but the effects remain unsatisfactory, highlighting the urgent need for novel immune-related therapy targets. In recent years, more and more studies have pointed out the associations between certain transmembrane (TMEM) family proteins and tumor progression, but the role of TMEM205 remains unclear. In this study, we analyzed the RNA-seq and clinical data of 371 patients from The Cancer Genome Atlas (TCGA) and found significant differential expression of TMEM205 between normal and tumor tissues (P < 0.001). Low TMEM205 expression was also found to be independently associated with poor overall survival (OS; p = 0.032) and poor disease-specific survival (DSS; p = 0.002) in multivariate Cox regression analyses. RNA-seq and clinical data from hepatocellular carcinoma patients in the International Cancer Genome Consortium (ICGC) also showed significant differential expression of TMEM205 (P < 0.001) and association between low TMEM205 expression and poor survival (P < 0.001). We also used the Estimate the Proportion of Immune and Cancer cells (EPIC) tool to estimate the proportions of various immune cells in the tumor tissues. A correlation analysis was conducted, and TMEM205 expression in tumor tissues was found to be significantly associated with the proportion of macrophages (Pearson r = 0.45, p < 0.0001). A negative correlation was found between TMEM205 expression and M2 macrophage markers (CD163, EGR2, and MS4A4A) and between TMEM205 expression and regulatory T cell (Treg) markers (CCR8, STAT5B, and IL2RA), while a positive correlation was found between TMEM205 expression and the proportion of CD8+ T cells (Pearson r = 0.26, p < 0.0001). In conclusion, TMEM205 might improve HCC patients' prognosis by reducing the levels of immunosuppressive cells (M2 macrophages and Tregs) and facilitating the infiltration of cytotoxic T cells into the tumor microenvironment. Therefore, TMEM205 has potential as a prognostic biomarker and immunotherapy agent in combination therapy regimens for HCC.
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Introduction: The alpha-fetoprotein (AFP) model is superior to the Milan criteria in predicting the recurrence of hepatocellular carcinoma (HCC) after liver transplantation in European and Latin American populations. The purpose of this study was to determine the predictive value of the AFP model in Chinese hepatitis B virus (HBV)-related cirrhosis HCC patients. Methods: A total of 189 patients with HBV-related cirrhotic HCC were included. The recurrence rate and survival rate were estimated, and predictability was assessed by the Net Reclassification Improvement (NRI) method. Results: Of the 189 patients, patients with an AFP score >2 had a higher recurrence rate at 5 years (48.94 vs. 13.53%, p < 0.05) and lower survival rate (43.96 vs. 68.97%, p < 0.05). Considering patients within the Milan criteria, a higher 5-year recurrence rate and lower survival rate were observed in patients with an AFP model score >2 points compared to patients with a score of ≤ 2 points (recurrence rate: 58.75 vs. 12.98%, p < 0.05; survival rate: 28.57 vs. 67.41%, p = 0.047). NRI analysis showed that the AFP model exhibited superior predictability as compared to the Milan criteria. Conclusions: The AFP model may be used as a selection tool for Chinese HBV patients who require liver transplantation due to HCC.
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BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can induce a stronger regenerative ability than traditional 2-stage hepatectomy (TSH). ALPPS has become popular for achieving fast hypertrophy in patients with an insufficient future liver remnant (FLR). However, ALPPS is associated with high morbidity and mortality. Partial ALPPS is a variation that may decrease the morbidity and mortality. The purpose of this study was to perform a meta-analysis comparing outcomes of ALLPS and partial ALLPS. METHODS: PubMed, Embase, and Cochrane Library databases were searched for studies comparing partial ALPPS and complete ALPPS up to April 2019. Included studies were assessed by the Newcastle-Ottawa Scale (NOS). Weighted mean difference (WMD)/standard mean difference (SMD) and odds ratios (OR) with 95% confidence intervals (CIs) were calculated to compare FLR, time interval between stages, postoperative complications, and mortality between partial and complete ALPPS. RESULTS: Four studies including 124 patients were included. FLR hypertrophy of partial ALPPS was comparable to complete ALPPS (p = 0.09). The time interval between stages was not different between the 2 procedures (p = 0.57). The postoperative complications rate of partial ALPPS was significantly lower than that of complete ALPPS (OR = 0.38; p = 0.03). The mortality rate of partial ALLPS (4.9%) was lower than that of complete ALLPS (18.9%), but the difference was not significant (OR = 0.37; p = 0.12). CONCLUSIONS: Partial ALLPS is associated with similar FLR hypertrophy and time interval between stages as complete ALLPS, and a lower complication rate. Further studies are needed to examine patient selection and outcomes of the 2 procedures.