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1.
Hepatol Int ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664292

RESUMO

INTRODUCTION: Non-selective beta-blockers (NSBB) are used for primary prophylaxis in patients with liver cirrhosis and high-risk varices (HRVs). Assessing therapeutic response is challenging due to the invasive nature of hepatic venous pressure gradient (HVPG) measurement. This study aims to define a noninvasive machine-learning based approach to determine response to NSBB in patients with liver cirrhosis and HRVs. METHODS: We conducted a prospective study on a cohort of cirrhotic patients with documented HRVs receiving NSBB treatment. Patients were followed-up with clinical and elastography appointments at 3, 6, and 12 months after NSBB treatment initiation. NSBB response was defined as stationary or downstaging variceal grading at the 12-month esophagogastroduodenoscopy (EGD). In contrast, non-response was defined as upstaging variceal grading at the 12-month EGD or at least one variceal hemorrhage episode during the 12-month follow-up. We chose cut-off values for univariate and multivariate model with 100% specificity. RESULTS: According to least absolute shrinkage and selection operator (LASSO) regression, spleen stiffness (SS) and liver stiffness (LS) percentual decrease, along with changes in heart rate (HR) at 3 months were the most significant predictors of NSBB response. A decrease > 11.5% in SS, > 16.8% in LS, and > 25.3% in HR was associated with better prediction of clinical response to NSBB. SS percentual decrease showed the highest accuracy (86.4%) with high sensitivity (78.8%) when compared to LS and HR. The multivariate model incorporating SS, LS, and HR showed the highest discrimination and calibration metrics (AUROC = 0.96), with the optimal cut-off of 0.90 (sensitivity 94.2%, specificity 100%, PPV 95.7%, NPV 100%, accuracy 97.5%).

2.
J Clin Transl Hepatol ; 11(6): 1291-1307, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37719963

RESUMO

Background and Aims: Identification of prognostic factors for hepatocellular carcinoma (HCC) opens new perspectives for therapy. Circulating and cellular onco-miRNAs are noncoding RNAs which can control the expression of genes involved in oncogenesis through post-transcriptional mechanisms. These microRNAs (miRNAs) are considered novel prognostic and predictive factors in HCC. The apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) contributes to the quality control and processing of specific onco-miRNAs and is a negative prognostic factor in several tumors. The present work aims to: a) define APE1 prognostic value in HCC; b) identify miRNAs regulated by APE1 and their relative target genes and c) study their prognostic value. Methods: We used The Cancer Genome Atlas (commonly known as TCGA) data analysis to evaluate the expression of APE1 in HCC. To identify differentially-expressed miRNAs (DEmiRNAs) upon APE1 depletion through specific small interfering RNA, we used NGS and nanostring approaches in the JHH-6 HCC tumor cell line. Bioinformatics analyses were performed to identify signaling pathways involving APE1-regulated miRNAs. Microarray analysis was performed to identify miRNAs correlating with serum APE1 expression. Results: APE1 is considerably overexpressed in HCC tissues compared to normal liver, according to the TCGA-liver HCC (known as LIHC) dataset. Enrichment analyses showed that APE1-regulated miRNAs are implicated in signaling and metabolic pathways linked to cell proliferation, transformation, and angiogenesis, identifying Cyclin Dependent Kinase 6 and Lysosomal Associated Membrane Protein 2 as targets. miR-33a-5p, miR-769, and miR-877 are related to lower overall survival in HCC patients. Through array profiling, we identified eight circulating DE-miRNAs associated with APE1 overexpression. A training phase identified positive association between sAPE1 and miR-3180-3p and miR-769. Conclusions: APE1 regulates specific miRNAs having prognostic value in HCC.

3.
Antibiotics (Basel) ; 12(3)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36978310

RESUMO

There have been considerable advances in the treatment of diverticular disease in recent years. Antibiotics are frequently used to treat symptoms and prevent complications. Rifaximin, a non-absorbable antibiotic, is a common therapeutic choice for symptomatic diverticular disease in various countries, including Italy. Because of its low systemic absorption and high concentration in stools, it is an excellent medicine for targeting the gastrointestinal tract, where it has a beneficial effect in addition to its antibacterial properties. Current evidence shows that cyclical rifaximin usage in conjunction with a high-fiber diet is safe and effective for treating symptomatic uncomplicated diverticular disease, while the cost-effectiveness of long-term treatment is unknown. The use of rifaximin to prevent recurrent diverticulitis is promising, but further studies are needed to confirm its therapeutic benefit. Unfortunately, there is no available evidence on the efficacy of rifaximin treatment for acute uncomplicated diverticulitis.

4.
Diagnostics (Basel) ; 13(3)2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36766534

RESUMO

Pylephlebitis, defined as infective thrombophlebitis of the portal vein, is a rare condition with an incidence of 0.37-2.7 cases per 100,000 person-years, which can virtually complicate any intra-abdominal or pelvic infections that develop within areas drained by the portal venous circulation. The current systematic review aimed to investigate the etiology behind pylephlebitis in terms of pathogens involved and causative infective processes, and to report the most common symptoms at clinical presentation. We included 220 individuals derived from published cases between 1971 and 2022. Of these, 155 (70.5%) were male with a median age of 50 years. There were 27 (12.3%) patients under 18 years of age, 6 (2.7%) individuals younger than one year, and the youngest reported case was only 20 days old. The most frequently reported symptoms on admission were fever (75.5%) and abdominal pain (66.4%), with diverticulitis (26.5%) and acute appendicitis (22%) being the two most common causes. Pylephlebitis was caused by a single pathogen in 94 (42.8%) cases and polymicrobial in 60 (27.2%) cases. However, the responsible pathogen was not identified or not reported in 30% of the included patients. The most frequently isolated bacteria were Escherichia coli (25%), Bacteroides spp. (17%), and Streptococcus spp. (15%). The treatment of pylephlebitis consists initially of broad-spectrum antibiotics that should be tailored upon bacterial identification and continued for at least four to six weeks after symptom presentation. There is no recommendation for prescribing anticoagulants to all patients with pylephlebitis. However, they should be administered in patients with thrombosis progression on repeat imaging or persistent fever despite proper antibiotic therapy to increase the rates of thrombus resolution or decrease the overall mortality, which is approximately 14%.

5.
Technol Cancer Res Treat ; 21: 15330338221132924, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36537076

RESUMO

Background: Hepatic resection, radiofrequency ablation (RF), and liver transplantation (LT) represent the only available curative treatments for early stage hepatocellular carcinoma (HCC). Various studies showed that the 5-year overall survival (OS) rate reaches ∼70% after resection and ∼60% after RF. Objective: To improve the success rate of curative therapies and consequently the OS, an improvement in patients' selection and management should be pursued. In this regard, microRNAs (miRNAs) can be helpful prognostic biomarkers. Materials and Methods: In this retrospective study, a miRNA array profiling was performed on 34 HCC blood samples which is collected before therapy (T0), 1 month (T1), and 6 months (T2) after curative treatments (resection and RF) to identify noninvasive biomarker candidates for therapy response and OS. MiRNAs were validated in 80 blood HCC samples using quantitative real-time PCR (qRT-PCR). Patients were divided into complete responder (CR) and partial responder and progressive disease (PRPD). Results: Among the selected miRNAs, miR-3201 is significantly associated with treatment response in the validation phase, showing a 23% reduction (P = .026) in CR compared to PRPD. MiR-3201 was able to distinguish CR from PRPD (area under the curve [AUC] = 0.69, 71% sensitivity, 70% specificity, P = .0036). Furthermore, lower levels of miR-3201 were associated with longer OS (hazard ratio [HR] = 2.61, P = .0006). Conclusions: Blood miR-3201 could be used as a prognostic biomarker for curative therapy response and OS in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Prognóstico , Estudos Retrospectivos
6.
Clin Case Rep ; 10(11): e6491, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36381054

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease and is associated with cystic manifestation in the liver. Patients with ADPKD are at higher risk for hernias, here we present an image of an incisional hernia full of multiple liver cysts.

7.
Diagnostics (Basel) ; 12(10)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36292205

RESUMO

Introduction: Hepatocellular carcinoma (HCC) is the sixth most diagnosed malignancy and the fourth leading cause of cancer-related death worldwide, with poor overall survival despite available curative treatments. One of the most crucial factors influencing survival in HCC is recurrence. The current study aims to determine factors associated with early recurrence of HCC in patients with BCLC Stage 0 or Stage A treated with surgical resection or local ablation. Materials and Methods: We retrospectively enrolled 58 consecutive patients diagnosed with HCC within BCLC Stage 0 or Stage A and treated either by surgical resection or local ablation with maximum nodule diameter < 50 mm. In the first year of follow-up after treatment, imaging was performed regularly one month after treatment and then every three months. Each case was discussed collectively by the Liver Multidisciplinary Group to decide diagnosis, treatment, follow-up, and disease recurrence. Variables resulting in statistically significant difference were then studied by Cox regression analysis; univariately and then multivariately based on forward stepwise Cox regression. Results are represented in hazard ratio (H.R.) with 95% confidence interval (C.I.). Results: There was no statistically significant difference in recurrence rates (34.8 vs. 45.7%, log-rank test, p = 0.274) between patients undergoing surgical resection and local ablation, respectively. Early recurrence was associated with male gender (HR 2.5, 95% C.I. 1.9−3.1), nodule diameter > 20 mm (HR 4.5, 95% C.I. 3.9−5.1), platelet count < 125 × 103 cell/mm3 (HR 1.6, 95% C.I. 1.2−1.9), platelet-lymphocyte ratio < 95 (HR 2.1, 95% C.I. 1.7−2.6), lymphocyte-monocyte ratio < 2.5 (HR 1.9, 95% C.I. 1.4−2.5), and neutrophil-lymphocyte ratio > 2 (HR 2.7, 95% C.I. 2.2−3.3). Discussion and Conclusions: Our results are in line with the current literature. Male gender and tumor nodule dimension are the main risk factors associated with early HCC recurrence. Platelet count and other combined scores can be used as predictive tools for early HCC recurrence, although more studies are needed to define cut-offs.

8.
J Pers Med ; 12(7)2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35887603

RESUMO

NAFLD is the most common cause of abnormality in liver function tests. NAFLD is considered a potential cardiovascular risk factor and is linked to cardiovascular risk factors such as obesity, hypertension, type 2 diabetes, and dyslipidemia. Few previous studies have investigated whether NAFLD could be independently associated with cognitive impairment. The current study aims to find a possible role of NAFLD in the development of subcortical vascular dementia (sVaD). We considered NAFLD as a possible independent vascular risk factor or, considering its metabolic role, associated with other commonly accepted sVaD risk factors, i.e., lack of folate, vitamin B12, and vitamin D-OH25, and increased levels of homocysteine. We studied 319 patients diagnosed with sVaD. All patients underwent an abdominal ultrasound examination to classify steatosis into four levels (1-none up to 4-severe). sVaD patients were divided into two groups according to the presence or absence of NAFLD. Our results demonstrated a strong correlation between NAFLD and sVaD. Patients with the two comorbidities had worse neuropsychological outcomes and a worse metabolic profile. We also found a robust relationship between NAFLD and severe vitamin B12, folate, vitamin D hypovitaminosis, and higher hyperhomocysteinemia levels. This way, it is evident that NAFLD contributes to a more severe metabolic pathway. However, the strong relationship with the three parameters (B12, folate and vitamin D, and homocysteinemia) suggests that NAFLD can contribute to a proinflammatory condition.

9.
Biomedicines ; 10(2)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35203473

RESUMO

Acetylsalicylic acid (ASA) is one of the most commonly used drugs in the world. It derives from the extract of white willow bark, whose therapeutic potential was known in Egypt since 1534 BC. ASA's pharmacological effects are historically considered secondary to its anti-inflammatory, platelet-inhibiting properties; however, human studies demonstrating a pro-inflammatory effect of ASA exist. It is likely that we are aware of only part of ASA's mechanisms of action; moreover, the clinical effect is largely dependent on dosages. During the past few decades, evidence of the anti-infective properties of ASA has emerged. We performed a review of such research in order to provide a comprehensive overview of ASA and viral, bacterial, fungal and parasitic infections, as well as ASA's antibiofilm properties.

10.
Diagnostics (Basel) ; 12(2)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35204465

RESUMO

Hepatocellular Carcinoma (HCC) is the sixth most common cancer in the world. Patients with intermediate stage (Barcelona Clinic Liver Cancer, B stage) hepatocellular carcinoma (HCC) have been able to benefit from TACE (transarterial chemoembolization) as a treatment option. MicroRNAs (miRNAs), i.e., a subclass of non-coding RNAs (ncRNAs), participate in post-transcriptional gene regulation processes and miRNA dysfunction has been associated with apoptosis resistance, cellular proliferation, tumor genesis, and progression. Only a few studies have investigated the role of miRNAs as biomarkers predicting TACE treatment response in HCC. Here, we review the studies' characteristics from a radiological point of view, also correlating data with radiological images chosen from the cases of our institution.

11.
Brain Sci ; 11(12)2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34942871

RESUMO

Hepatitis C Virus (HCV), despite being a hepatotropic virus, is the causative agent of many systemic disorders, such as vasculitis, autoimmune diseases, lymphoproliferative disorders, and a broad spectrum of neurological and psychiatric manifestations. Although symptoms have been misdiagnosed or underdiagnosed, only recently, evidence of direct (inflammatory) or indirect (immune-mediated) HCV-dependent cerebral effects has been established. HCV infection can promote acute inflammatory response, pro-coagulative status and ischemic disorders, and neurodegeneration. These effects rely on cerebral HCV replication, possibly mediated by blood-brain barrier alterations. Further study is needed to better understand the HCV-related mechanisms of brain damage.

12.
Healthcare (Basel) ; 9(8)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34442092

RESUMO

In late December 2019, a novel coronavirus (lately referred to as SARS-CoV-2) spread in the city of Wuhan, China, causing an outbreak of unusual viral pneumonia. In many people, the disease is mild and self-limiting, but in a considerable number of patients, the disease may present more severe or even fatal. Therefore, determining which patients are at higher risk of developing a more severe disease is critical. Some studies have been focused on serum and fecal calprotectin to evaluate COVID-19 disease progression and possible complications. Some assumptions can be made: (1) serum calprotectin may efficiently predict the prognosis of COVID-19 patients; (2) fecal calprotectin may appear high in COVID-19 patients due to the double hit mechanism to the intestine (inflammatory and ischemic); (3) a relationship between the complement system and neutrophil activation contributes to the procoagulant status seen in COVID-19 patients; (4) some patients may develop severe gastro-intestinal complications and fecal calprotectin can be used to monitor intestinal disease activity levels.

13.
World J Gastroenterol ; 27(22): 3130-3137, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34168414

RESUMO

BACKGROUND: One third of coronavirus disease 2019 (COVID-19) patients have gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has been detected in stool samples of approximately 50% of COVID-19 individuals. Fecal calprotectin is a marker of gastrointestinal inflammation in the general population. AIM: To investigate if fecal calprotectin correlates with SARS-CoV-2 intestinal shedding in COVID-19 patients with pneumonia. METHODS: Patients with SARS-CoV-2 pneumonia admitted to the Infectious Disease Unit (University Hospital of Trieste, Italy) from September to November 2020 were consecutively enrolled in the study. Fecal samples were collected and analyzed for quantification of fecal calprotectin (normal value < 50 mg/kg) and SARS-CoV-2 RNA presence by polymerase chain reaction (PCR). Inter-group differences were determined between patients with and without diarrhea and patients with and without detection of fecal SARS-CoV-2. RESULTS: We enrolled 51 adults (40 males) with SARS-CoV-2 pneumonia. Ten patients (20%) presented with diarrhea. Real-time-PCR of SARS-CoV-2 in stools was positive in 39 patients (76%), in all patients with diarrhea (100%) and in more than two thirds (29/41, 71%) of patients without diarrhea. Obesity was one of the most common comorbidities (13 patients, 25%); all obese patients (100%) (P = 0.021) tested positive for fecal SARS-CoV-2. Median fecal calprotectin levels were 60 mg/kg [interquartile range (IQR) 21; 108]; higher fecal calprotectin levels were found in the group with SARS-CoV-2 in stools (74 mg/kg, IQR 29; 132.5) compared to the group without SARS-CoV-2 (39 mg/kg, IQR 14; 71) (P < 0.001). CONCLUSION: High fecal calprotectin levels among COVID-19 patients correlate with SARS-CoV-2 detection in stools supporting the hypothesis that this virus can lead to bowel inflammation and potentially to the 'leaky gut' syndrome.


Assuntos
COVID-19 , Complexo Antígeno L1 Leucocitário/análise , Eliminação de Partículas Virais , Adulto , COVID-19/diagnóstico , Fezes/química , Feminino , Humanos , Itália , Masculino , RNA Viral , SARS-CoV-2
14.
Pathogens ; 10(5)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946817

RESUMO

Infliximab is an IgG1 antitumor necrosis factor monoclonal antibody that is commonly used to treat inflammatory bowel disease (IBD) and other autoimmune disorders. However, it is known to increase the risk of reactivation of latent tuberculosis (LTBI) due to its capability to disrupt TB granulomas. We describe a case of extrapulmonary TB in a patient with ulcerative colitis who was treated with Infliximab after a negative Quantiferon Test. In addition, we report briefly on the current controversy about the appropriateness, interval, and methods for the repeated screening of latent TB in IBD patients that are treated with antitumor necrosis factor alpha (TNF-α) antibodies.

15.
J Ultrasound ; 24(1): 67-73, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32304009

RESUMO

BACKGROUND: Spleen stiffness (SS) has gained a lot of interest in the context of liver cirrhosis and portal hypertension stratification. However, there is a paucity of data on confounding factors that may alter SS values. METHODS: Between January 2018 and October 2019, we enrolled 120 healthy subjects and 117 patients with hepatitis C virus (HCV) infection who did not have significant liver fibrosis (i.e., F0-1). Abdominal ultrasound evaluation was performed on each individual to measure portal vein diameter, portal flow velocity, spleen bipolar diameter, and splenic area. We also performed liver and spleen elastography. RESULTS: HCV patients had higher SS (p < 0.001), portal vein diameter (p = 0.031), portal flow velocity (p = 0.035), spleen bipolar diameter (p = 0.042) and area (p = 0.025), and ALT levels (p < 0.001). Linear regression models showed that SS increased by 3.220 kPa for each mm of portal vein diameter, by 0.7 kPa for each cm/s of portal flow velocity, by 2.239 kPa for each cm of spleen bipolar diameter, and by 0.233 kPa for each cm2 of spleen area. Patients with HCV infection were stratified according to median ALT levels (i.e. 32 IU/L). SS and spleno-portal axis parameters were significantly higher in patients with an ALT level > 32 IU/L. Besides, the relationship between SS and ALT was described by cubic polynomial regression according to the following equation: 11.735 + 0.404 (ALT)1 - 0.002 (ALT)2 + 4.26 × 10-6 (ALT)3. CONCLUSIONS: Our results bring new light to the role of inflammation as a confounding factor for SS measurement. Therefore, particular attention should be paid to serum transaminase for a correct evaluation of spleen elastography.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatite C Crônica , Adulto , Idoso , Alanina Transaminase , Feminino , Hepatite C Crônica/diagnóstico por imagem , Hepatite C Crônica/patologia , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Baço/diagnóstico por imagem
16.
Antibiotics (Basel) ; 11(1)2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-35052907

RESUMO

The liver is the primary site of drug metabolism, which can be altered by a variety of diseases affecting the liver parenchyma, especially in patients with liver cirrhosis. The use of antibiotics in patients with cirrhosis is usually a matter of concern for physicians, given the lack of practical knowledge for drug choice and eventual dose adjustments in several clinical scenarios. The aim of the current narrative review is to report, as broadly as possible, basic, and practical knowledge that any physician should have when approaching a patient with liver cirrhosis and an ongoing infection to efficiently choose the best antibiotic therapy.

17.
Anal Bioanal Chem ; 413(5): 1303-1312, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33294938

RESUMO

Intense label-free surface-enhanced Raman scattering (SERS) spectra of serum samples were rapidly obtained on Ag plasmonic paper substrates upon 785 nm excitation. Spectra from the hepatocellular carcinoma (HCC) patients showed consistent differences with respect to those of the control group. In particular, uric acid was found to be relatively more abundant in patients, while hypoxanthine, ergothioneine, and glutathione were found as relatively more abundant in the control group. A repeated double cross-validation (RDCV) strategy was applied to optimize and validate principal component analysis-linear discriminant analysis (PCA-LDA) models. An analysis of the RDCV results indicated that a PCA-LDA model using up to the first four principal components has a good classification performance (average accuracy was 81%). The analysis also allowed confidence intervals to be calculated for the figures of merit, and the principal components used by the LDA to be interpreted in terms of metabolites, confirming that bands of uric acid, hypoxanthine, ergothioneine, and glutathione were indeed used by the PCA-LDA algorithm to classify the spectra.


Assuntos
Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Análise Espectral Raman/métodos , Idoso , Carcinoma Hepatocelular/química , Análise Discriminante , Humanos , Neoplasias Hepáticas/química , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal
18.
J Clin Med ; 9(11)2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33218203

RESUMO

Mammalian organisms form intimate interfaces with commensal and pathogenic gut microorganisms. Increasing evidence suggests a close interaction between gut microorganisms and the enteric nervous system (ENS), as the first interface to the central nervous system. Each microorganism can exert a different effect on the ENS, including phenotypical neuronal changes or the induction of chemical transmitters that interact with ENS neurons. Some pathogenic bacteria take advantage of the ENS to create a more suitable environment for their growth or to promote the effects of their toxins. In addition, some commensal bacteria can affect the central nervous system (CNS) by locally interacting with the ENS. From the current knowledge emerges an interesting field that may shape future concepts on the pathogen-host synergic interaction. The aim of this narrative review is to report the current findings regarding the inter-relationships between bacteria, viruses, and parasites and the ENS.

19.
Sci Rep ; 10(1): 18967, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144628

RESUMO

The weighted gene co-expression network analysis (WGCNA) has been used to explore gene expression datasets by constructing biological networks based on the likelihood expression profile among genes. In recent years, WGCNA found application in biomarker discovery studies, including miRNA. Serum samples from 20 patients with hepatocellular carcinoma (HCC) were profiled through miRNA 3.0 gene array and miRNAs biomarker candidates were identified through WGCNA. Results were validated by qRT-PCR in 102 HCC serum samples collected at diagnosis. WGCNA identified 16 miRNA modules, nine of them were significantly associated with the clinical characteristics of the patient. The Red module had a significant negative correlation with patients Survival (- 0.59, p = 0.007) and albumin (- 0.52, p = 0.02), and a positive correlation with PCR (0.61, p = 0.004) and alpha-fetoprotein (0.51, p = 0.02). In the red module, 16 circulating miRNAs were significantly associated with patient survival. MiR-3185 and miR-4507 were identified as predictors of patient survival after the validation phase. At diagnosis, high expression of circulating miR-3185 and miR-4507 identifies patients with longer survival (HR 2.02, 95% CI 1.10-3.73, p = 0.0086, and HR of 1.75, 95% CI 1.02-3.02, p = 0.037, respectively). Thought a WGCNA we identified miR-3185 and miR-4507 as promising candidate biomarkers predicting a longer survival in HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , MicroRNA Circulante/metabolismo , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Cancers (Basel) ; 12(10)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003646

RESUMO

The clinical outcome of hepatocellular carcinoma (HCC) treatment remains unsatisfactory, contributing to the high mortality of HCC worldwide. Circulating miRNAs have the potential to be a predictor of therapy response. Microarray profiling was performed in serum samples of 20 HCC patients before treatment. Circulating miRNAs associated with treatment response were validated in 86 serum HCC samples using the qRT-PCR system. Patients were treated either with curative treatments (resection or radiofrequency) or trans-arterial chemoembolization (TACE), and grouped according to therapy response in complete responders (CR) and partial responders or progressive disease (PRPD), following mRECIST criteria. Four miRNA candidates from the discovery phase (miR-4443, miR-4454, miR-4492, and miR-4530) were validated. Before therapy, miR-4454 and miR-4530 were up-regulated in CR to curative treatments (2.83 fold, p = 0.02 and 2.33 fold, p = 0.008, respectively) and were able to differentiate CR from PRPD (area under the curve (AUC) = 0.74, sens/spec 79/63% and AUC = 0.77, sens/spec 72/73%). On the contrary, miR-4443 was 1.95 times down-regulated in CR (p = 0.05) with an AUC of 0.72 (sens = 70%, spec = 60%) in distinguishing CR vs. PRPD). The combination of the three miRNAs was able to predict the response to curative treatment with an AUC of 0.84 (sens = 72%, spec = 75%). The higher levels of miR-4454 and miR-4530 in were associated to longer overall survival (HR = 2.79, p = 0.029 and HR = 2.97, p = 0.011, respectively). Before TACE, miR-4492 was significantly up-regulated in CR patients (FC = 2.67, p = 0.01) and able to differentiate CR from PRPD (AUC = 0.84, sens/spec 84.6/71%). We demonstrated that different miRNAs predictors can be used as potential prognostic circulating biomarkers according to the selected treatment for HCC.

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