Performance For Hepatocellular Carcinoma Research Articles

Computed tomography-based radiomics to predict early recurrence of hepatocellular carcinoma post-hepatectomy in patients background on cirrhosis.

The prognosis for hepatocellular carcinoma (HCC) in the presence of cirrhosis is unfavourable, primarily attributable to the high incidence of recurrence. To develop a machine learning model for predicting early recurrence (ER) of post-hepatectomy HCC in patients with cirrhosis and to stratify patients' overall survival (OS) based on the predicted risk of recurrence. In this retrospective study, 214 HCC patients with cirrhosis who underwent curative hepatectomy were examined. Radiomics feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination methods. Clinical-radiologic features were selected through univariate and multivariate logistic regression analyses. Five machine learning methods were used for model comparison, aiming to identify the optimal model. The model's performance was evaluated using the receiver operating characteristic curve [area under the curve (AUC)], calibration, and decision curve analysis. Additionally, the Kaplan-Meier (K-M) curve was used to evaluate the stratification effect of the model on patient OS. Within this study, the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic features. In the training cohort, this model attained an AUC of 0.844, while in the validation cohort, it achieved a value of 0.790. The K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients' OS. The combined model, integrating both radiomics and clinical-radiologic characteristics, exhibited excellent performance in HCC with cirrhosis. The K-M curves assessing OS revealed statistically significant differences.

A distinct microbiota signature precedes the clinical diagnosis of hepatocellular carcinoma

ABSTRACT Oral, gut, and tumor microbiota have been implicated as important regulators in the carcinogenesis and progression of gastrointestinal malignancies. However, few studies focused on the existence and association of resident microbes within different body regions. Herein, we aim to reveal the durability of the oral-gut-tumor microbiome and its diagnostic performance in hepatocellular carcinoma (HCC). Our study included two cohorts: a retrospective discovery cohort of 364 HBV-HCC patients and 160 controls with oral or fecal samples, a prospective validation cohort of 91 cases, and 124 controls for matching samples, as well as 48 HBV, and 39 HBV-cirrhosis patients for gut microbial patterns examined by 16S rRNA gene sequencing. With the random forest analysis, 10 oral and 9 gut genera that could distinguish HCC from controls in the retrospective cohort were validated among the prospective matching participants, with area under the curve (AUC) values of 0.7971 and 0.8084, respectively. When influential taxa were merged, the AUC of the consistent classifier increased to 0.9405. The performance continued to improve to 0.9811 when combined with serum levels of alpha-fetoprotein (AFP). Specifically, microbial biomarkers represented by Streptococcus displayed a constantly increasing trend during the disease transition. Furthermore, the presence of several dominant microbiota species was confirmed in hepatic tumor and non-tumor tissues with fluorescence in situ hybridization (FISH) and 5 R 16S rRNA gene sequencing. Overall, our findings based on the oral-gut-tumor microbiota provide a reliable approach for the early detection of HCC.

Diagnostic value of magnetic resonance imaging features of microvascular invasion in hepatocellular carcinoma: a meta-analysis.

PURPOSE This systematic review and meta-analysis of conventional enhanced magnetic resonance imaging (MRI) were conducted to evaluate the diagnostic performance of imaging features of microvascular invasion (MVI) prediction in hepatocellular carcinoma (HCC). METHODS Relevant studies on diagnosing MVI in HCC by MRI were searched in the MEDLINE, PUBMED, EMBASE, Cochrane library, and Web of Science databases. The pooled mean sensitivity and specificity were calculated using a random effects model. The corresponding positive likelihood ratio (PLR), negative likelihood ratio (NLR), and pooled diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic (SROC) curve was used to summarize the overall diagnostic accuracy. Diagnostic performance was evaluated by determining the area under the curve (AUC). Regression analysis by subgroup and sensitivity analysis were used to explore potential sources of heterogeneity. RESULTS A total of 19 studies comprising 1920 HCC patients with 2033 tumors were ultimately enrolled. For the signs of the presence of peritumoral enhancement in the arterial phase, peritumoral hypointensity in the hepatobiliary phase, irregular non-smooth margin, and rim-like enhancement in the arterial phase, the pooled sensitivity values, the pooled specificity values, the pooled PLR values, the pooled NLR values, the pooled DOR values, and the values of the AUC of SROC curves were determined. CONCLUSION The conventional MRI features for predicting MVI showed poor diagnostic performance in HCC. Only signs of the presence of peritumoral enhancement in the arterial phase showed a moderate diagnostic accuracy.

Non-invasive diagnosis strategy of hepatocellular carcinoma in low-risk population

AimsWith prevalence of hepatocellular carcinoma (HCC) in low-risk population (LRP), establishing a non-invasive diagnostic strategy becomes increasingly urgent to spare unnecessary biopsies in this population. The purposes of this study were to find characterisics of HCC and to establish a proper non-invasive method to diagnose HCC in LRP.MethodsA total of 681 patients in LRP (defined as the population without cirrhosis, chronic HBV infection or HCC history) were collected from 2 institutions. The images of computed tomography (CT) and magnetic resonance imaging (MRI) were manually analysed. We divided the patients into the training cohort (n = 324) and the internal validating cohort (n = 139) by admission time in the first institution. The cohort in the second institution was viewed as the external validation (n = 218). A multivariate logistic regression model incorporating both imaging and clinical independent risk predictors was developed. C-statistics was used to evaluate the diagnostic performance.ResultsBesides the major imaging features of HCC (non-rim enhancement, washout and enhancing capsule), tumor necrosis or severe ischemia (TNSI) on imaging and two clinical characteristics (gender and alpha fetoprotein) were also independently associated with HCC diagnosis (all P < 0.01). A clinical model (including 3 major features, TNSI, gender and AFP) was built to diagnose HCC and achieved good diagnostic performance (area under curve values were 0.954 in the training cohort, 0.931 in the internal validation cohort and 0.902 in the external cohort).ConclusionsThe clinical model in this study developed a satisfied non-invasive diagnostic performance for HCC in LRP.

Circulating Cell-Free DNA and DNA Integrity as Molecular Diagnostic Tools in Hepatocellular Carcinoma.

We assessed the ability to use circulating cell-free DNA (cfDNA) and the DNA integrity index (DNAII) to detect the transition from liver cirrhosis (LC) to hepatocellular carcinoma (HCC). Circulating cfDNA and DNAII were measured in 50 patients with advanced LC and 50 patients with HCC who were followed for 1 month after transarterial chemoembolization (TACE). Fifty healthy participants served as a control group. Real-time quantitative polymerase chain reaction (PCR) was used to measure circulating cfDNA concentration, and Alu-PCR was used to measure the concentration of Alu repeats, both short fragments (115 base pairs [bp]) and long fragments (247 bp). We compared liquid biopsy results with the relevant traditional markers. The HCC group showed significantly higher circulating cfDNA concentrations and DNAII values compared with the LC and control groups. No significant differences were found in circulating cfDNA concentrations and DNAII values between the LC and control groups. Circulating cfDNA concentrations decreased significantly after treatment (TACE); areas under the curve of circulating cfDNA concentration and DNAII values were significantly better than those of ɑ-fetoprotein and vascular endothelial growth factor in discriminating between LC and HCC. The combined use of DNAII with proteins induced by vitamin K absence or antagonist showed better diagnostic performance in HCC. Circulating cfDNA could have a potential role in monitoring HCC treatment.

Protein tyrosine phosphatase receptor type D (PTPRD)-mediated signaling pathways for the potential treatment of hepatocellular carcinoma: a narrative review.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide, and the methods for its treatment have shown limited efficacy. There is an urgent need to explore the underlying mechanism that are involved in hepatocarcinogenesis, contributing to find various signal molecular targets for HCC diagnosis, prevention and therapy. Recently, Various studies have illustrated protein tyrosine phosphatase receptor type D (PTPRD) is an important tumor-suppressor gene that is down-regulated in HCC and this downregulation occurs through its promoter hypermethylation. PTPRD is involved in the progression, migration, apoptosis, invasion and immune suppression of HCC. Also, PTPRD participates in several vital cellular signaling pathways, including PTPRD, signal transduction and activation of transcription 3 (STAT3), JAK, PTPRD, β-catenin, TCF, along with the PTPRD-CXCL8 axis, the PTPRD/phosphatidylinositol3-kinase (PI3K)/mammalian target of rapamycin (mTOR), and the PTPRD/PD-1/programmed death receptor ligand-1 (PD-L1) axis, thus playing an essential role in HCC. Therefore, PTPRD can be considered as a novel therapeutic target for HCC, and PTPRD-targeted therapeutics in combination with methylation inhibitors, immune checkpoint inhibitors and alternative targeted drugs maybe an innovative treatment method for HCC. However, clinical research of PTPRD-targeted therapies in HCC is greatly limited and tremendous efforts are strongly urged to evaluate its clinical performance in HCC. In this review, we summarized the physiological function and the significant effects of PTPRD and performed a comprehensive analysis of PTPRD-targeted strategies for HCC.

Role of Kupffer phase image using sonazoid on CEUS LI-RADS® and diagnostic performance for hepatocellular carcinoma

Role of Kupffer phase image using sonazoid on CEUS LI-RADS® and diagnostic performance for hepatocellular carcinoma

The Diagnostic Performance of lncRNAs from Blood Specimens in Patients with Hepatocellular Carcinoma: A Meta-Analysis.

Long noncoding RNAs (lncRNAs) are widely involved in the carcinogenesis and development of cancers. We conducted a meta-analysis to evaluate the diagnostic performance of lncRNAs in hepatocellular carcinoma (HCC). After the inclusion and exclusion process, relevant information was extracted. Heterogeneity between studies was evaluated, and data synthesis was conducted by employing a bivariate random-effects model. In total, 20 eligible studies were enrolled. The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.80-0.90) and 0.88 (95% CI, 0.82-0.92), respectively. The pooled positive likelihood ratio, pooled negative likelihood ratio, and pooled diagnostic odds ratio were 7.1 (95% CI, 4.9-10.2), 0.16 (95% CI, 0.11-0.23), and 44 (95% CI, 25-79), respectively. The results of the linear regression method and visual inspection of the Deeks funnel plot did not indicate significant publication bias. Our meta-analysis suggested that lncRNAs have high diagnostic performance for HCC and have the potential for clinical application.

STAT3: An Emerging Therapeutic Target for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a major global health problem and its treatment options have been limited. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor important for various cellular processes. Overexpression and constitutive activation of STAT3 have been frequently found in HCC and associated with poor prognosis. Ample evidence has shown that STAT3 plays pivotal roles in the initiation, progression, metastasis and immune suppression of HCC. Thus, STAT3 has attracted attention as a novel therapeutic target in HCC. Clinical trials have investigated STAT3-targeted therapeutics either as monotherapy or in combination with chemotherapeutic agents, immune checkpoint inhibitors and alternative targeted drugs. Some of these studies have yielded encouraging results. Particularly, napabucasin—a cancer stemness inhibitor targeting STAT3-driven gene transcription—has stood out with its promising clinical efficacy and safety profile. Nonetheless, clinical investigations of STAT3-targeted therapies in HCC are limited and more efforts are strongly urged to evaluate their clinical performance in HCC. Here, we provide a comprehensive review of the roles of STAT3 in HCC and follow by comprehensive analysis of STAT3 targeted strategies.

Circulating Tumor DNA and Hepatocellular Carcinoma.

There is a clear and unmet need for biomarkers in hepatocellular carcinoma (HCC). Circulating cell free deoxyribonucleic acid (cfDNA) is a fragmented DNA subtype, found in the blood circulation. Circulating tumor DNA (ctDNA) is the fraction of total cfDNA, which originates from the primary tumor or metastases in patients with cancer. Earlier studies reported that quantitative measurement cfDNA has diagnostic and prognostic role for HCC. More recently, improvement in next-generation sequencing technology and better understanding of genetic or epigenetic alteration of HCC have allowed comprehensive analysis of mutational and methylation landscape of ctDNA. Hotspot mutation panels and methylation panels have both shown promising performance. None of these tests have yet been validated in longitudinal cohorts for preclinical detection of HCC. In this article, the authors discuss the currently available ctDNA detection technologies, their diagnostic and prognostic performance in HCC, and future research directions.

Current noninvasive liver reserve models do not predict histological fibrosis severity in hepatocellular carcinoma

The Ishak scoring system has been used to stage liver fibrosis. Ten noninvasive liver reserve models were proposed to assess the severity of liver fibrosis, but their performance in hepatocellular carcinoma (HCC) is unknown. We aimed to evaluate the correlation between these models and severity of fibrosis in patients with HCC. A total 464 patients with HCC undergoing surgical resection were retrospectively analyzed. Multivariate logistic regression analysis was performed to determine independent factors associated with advanced fibrosis (Ishak score 4 or higher). There were no significant correlations between all noninvasive models and severity of fibrosis in HCC (p for trend all >0.1). In subgroup analysis, cirrhosis discriminant index (CDS) and Lok’s index in hepatitis B-, and fibrosis index based on 4 factors (FIB-4), CDS and Lok’s index in hepatitis C-associated HCC, best correlated with the severity of liver fibrosis. Low platelet count, prolonged prothrombin time, hepatitis C and multiple tumors were independently associated with advanced fibrosis. Among the 10 models, CDS was the best model to predict cirrhosis. Currently used noninvasive liver reserve models do not well correlate with severity of histological fibrosis in HCC. New noninvasive models are required to improve the predictive accuracy of liver fibrosis in HCC.

Optimisation of quantitative miRNA panels to consolidate the diagnostic surveillance of HBV-related hepatocellular carcinoma.

BackgroundCirculating microRNAs (miRNA) are biomarkers for several neoplastic diseases, including hepatocellular carcinoma (HCC). We performed a literature search, followed by experimental screening and validation in order to establish a miRNA panel in combination with the assessment of alpha-fetoprotein (AFP) levels and to evaluate its performance in HCC diagnostics.MethodsExpression of miRNAs was quantified by quantitative PCR (qPCR) in 406 serum samples from 118 Vietnamese patients with hepatitis B (HBV)-related HCC, 69 patients with HBV-related liver cirrhosis (LC), 100 chronic hepatitis B (CHB) patients and 119 healthy controls (HC).ResultsThree miRNAs (mir-21, mir-122, mir-192) were expressed differentially among the studied subgroups and positively correlated with AFP levels. The individual miRNAs mir-21, mir-122, mir192 or the triplex miRNA panel showed high diagnostic accuracy for HCC (HCC vs. CHB, AUC = 0.906; HCC vs. CHB+LC, AUC = 0.81; HCC vs. CHB+LC+HC, AUC = 0.854). When AFP levels were ≤20ng/ml, the triplex miRNA panel still was accurate in distinguishing HCC from the other conditions (CHB, AUC = 0.922; CHB+LC, AUC = 0.836; CHB+LC+HC, AUC = 0.862). When AFP levels were used in combination with the triplex miRNA panel, the diagnostic performance was significantly improved in discriminating HCC from the other groups (LC, AUC = 0.887; CHB, AUC = 0.948; CHB+LC, AUC = 0.887).ConclusionsThe three miRNAs mir-21, mir-122, mir-192, together with AFP, are biomarkers that may be applied to improve diagnostics of HCC in HBV patients, especially in HBV-related LC patients with normal AFP levels or HCC patients with small tumor sizes.

Combined Analysis of Serum Alpha-Fetoprotein and MAGE-A3-Specific Cytotoxic T Lymphocytes in Peripheral Blood for Diagnosis of Hepatocellular Carcinoma

We investigated the feasibility of the combined detection of HLA-A2/MAGE-A3 epitope-specific cytotoxic T lymphocytes (CTLs) and serum alpha-fetoprotein (AFP) for specific diagnosis of hepatocellular carcinoma (HCC). We detected the frequency of MAGE-A3 epitopes (p112–120, KVAELVHFL) in spontaneous CTLs in the peripheral blood of HCC patients, liver cirrhosis patients, and healthy subjects with HLA-A2/polypeptide complex (pentamer) detection technology. Eighty-five HCC cases, 38 liver cirrhosis cases, and 50 healthy cases who were HLA-A2-positive were selected from 175 HCC patients, 80 patients with liver cirrhosis, and 105 healthy volunteers, respectively. The frequency of HLA-A2-specific MAGE-A3+ CTLs in the HCC group was significantly higher than that in the other groups. Combined detection of MAGE-A3+ CTL frequency and serum AFP value had a higher specificity than either of the two indicators alone. The pentamer technique is helpful in distinguishing benign lesions and malignant lesions in the liver. Combined with serum AFP, it can improve the diagnosis performance for HCC, especially for AFP-negative cancer.

Identification of osteopontin as a novel marker for early hepatocellular carcinoma

The aim of this study was to identify a biomarker that could improve alpha-fetoprotein (AFP) performance in hepatocellular carcinoma (HCC) surveillance among patients with cirrhosis. We performed proteomic profiling of plasma from patients with cirrhosis or HCC and validated selected candidate HCC biomarkers in two geographically distinct cohorts to include HCC of different etiologies. Mass spectrometry profiling of highly fractionated plasma from 18 cirrhosis and 17 HCC patients identified osteopontin (OPN) as significantly up-regulated in HCC cases, compared to cirrhosis controls. OPN levels were subsequently measured in 312 plasma samples collected from 131 HCC patients, 76 cirrhosis patients, 52 chronic hepatitis C (CHC) and B (CHB) patients, and 53 healthy controls in two independent cohorts. OPN plasma levels were significantly elevated in HCC patients, compared to cirrhosis, CHC, CHB, or healthy controls, in both cohorts. OPN alone or in combination with AFP had significantly better area under the receiver operating characteristic curve, compared to AFP, in comparing cirrhosis and HCC in both cohorts. OPN overall performance remained higher than AFP in comparing cirrhosis and the following HCC groups: HCV-related HCC, HBV-associated HCC, and early HCC. OPN also had a good sensitivity in AFP-negative HCC. In a pilot prospective study including 22 patients who developed HCC during follow-up, OPN was already elevated 1 year before diagnosis. OPN was more sensitive than AFP for the diagnosis of HCC in all studied HCC groups. In addition, OPN performance remained intact in samples collected 1 year before diagnosis.