scholarly journals Platelets’ RNA as biomarker trove for differentiation of early-stage hepatocellular carcinoma from underlying cirrhotic nodules

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256739
Author(s):  
Walifa Waqar ◽  
Sidra Asghar ◽  
Sobia Manzoor
Keyword(s):  
Hepatocellular Carcinoma ◽  
Late Stage ◽  
Liquid Biopsy ◽  
Early Stage ◽  
Quantitative Real Time Pcr ◽  
Roc Curve Analysis ◽  
Mrna Content ◽  
Early Hcc ◽  
Rising Incidence ◽  
Specific Mrna

Background & aims Among the multiplicity of factors involved in rising incidence of hepatocellular carcinoma (HCC)-the second deadliest cancer, late diagnosis of early-stage HCC nodules originating from late-stage cirrhotic nodules is the most crucial. In recent years, Tumor-educated platelets (TEPs) have emerged as a strong multimodal tool to be used in liquid-biopsy of cancers because of changes in their mRNA content. This study assessed the reliability of selected mRNA repertoire of platelets as biomarkers to differentiate early HCC from late-stage cirrhotic nodules. Methods Quantitative real time PCR (qRT-PCR) was used to evaluate expression levels of selected platelets-specific mRNA between HCC patients compared to cirrhosis patients. ROC curve analysis assessed the sensitivity and specificity of the biomarkers. Results RhoA, CTNNB1 and SPINK1 showed a significant 3.3-, 3.2- and 3.18-folds upregulation, respectively, in HCC patients compared to cirrhosis patients while IFITM3 and SERPIND1 presented a 2.24-fold change. Strikingly, CD41+ platelets also demonstrated a marked difference of expression in HCC and cirrhosis groups. Conclusions Our study reports liquid biopsy-based platelets mRNA signature for early diagnosis of HCC from underlying cirrhotic nodules. Moreover, differential expression of CD41+ platelets in two groups provides new insights into a probable link between CD41 expression on platelets with the progression of cirrhosis to HCC.

Liquid biopsy in the clinical management of hepatocellular carcinoma

Gut ◽  
2020 ◽  
Vol 69 (11) ◽  
pp. 2025-2034 ◽  
Author(s):  
Johann von Felden ◽  
Teresa Garcia-Lezana ◽  
Kornelius Schulze ◽  
Bojan Losic ◽  
Augusto Villanueva
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Response ◽  
Liquid Biopsy ◽  
Clinical Management ◽  
Early Stage ◽  
Personalised Medicine ◽  
Precision Oncology ◽  
Early Hepatocellular Carcinoma ◽  
Populations At Risk ◽  
Circulating Tumour Dna

With increasing knowledge on molecular tumour information, precision oncology has revolutionised the medical field over the past years. Liquid biopsy entails the analysis of circulating tumour components, such as circulating tumour DNA, tumour cells or tumour-derived extracellular vesicles, and has thus come as a handy tool for personalised medicine in many cancer entities. Clinical applications under investigation include early cancer detection, prediction of treatment response and molecular monitoring of the disease, for example, to comprehend resistance patterns and clonal tumour evolution. In fact, several tests for blood-based mutation profiling are already commercially available and have entered the clinical field.In the context of hepatocellular carcinoma, where access to tissue specimens remains mostly limited to patients with early stage tumours, liquid biopsy approaches might be particularly helpful. A variety of translational liquid biopsy studies have been carried out to address clinical needs, such as early hepatocellular carcinoma detection and prediction of treatment response. To this regard, methylation profiling of circulating tumour DNA has evolved as a promising surveillance tool for early hepatocellular carcinoma detection in populations at risk, which might soon transform the way surveillance programmes are implemented. This review summarises recent developments in the liquid biopsy oncological space and, in more detail, the potential implications in the clinical management of hepatocellular carcinoma. It further outlines technical peculiarities across liquid biopsy technologies, which might be helpful for interpretation by non-experts.

A multicenter nonrandomized controlled trial to evaluate the efficacy of surgery versus radiofrequency ablation for small hepatocellular carcinoma (SURF cohort trial).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4581-4581
Author(s):  
Ryosuke Tateishi ◽  
Kiyoshi Hasegawa ◽  
Yoshikuni Kawaguchi ◽  
Tadatoshi Takayama ◽  
Namiki Izumi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Early Stage ◽  
Controlled Trial ◽  
Patient Characteristics ◽  
Small Hepatocellular Carcinoma ◽  
Multicenter Randomized Controlled Trial ◽  
Early Hcc ◽  
The Difference

4581 Background: In parallel with a multicenter randomized controlled trial that reported an equal recurrence-free survival (RFS) of early-stage hepatocellular carcinoma (HCC) patients who underwent either surgery (SUR) or radiofrequency ablation (RFA), we also enrolled HCC patients who fulfilled the enrollment criteria but did not give consent to participate in the RCT. Methods: All patients gave informed consent to participate in this study. Inclusion criteria were as follows: primary HCC with less than or equal to 3 tumors, each measuring 3 cm or smaller; without vascular invasion or extrahepatic metastasis; Child-Pugh score of 7 or less; and ages between 20 and 79 years. The feasibility for both treatments was confirmed by a joint chart review by surgeons and hepatologists. The primary endpoint was RFS and overall survival. A pre-specified interim analysis was performed to compare RFS. Results: Between April 2009 and August 2015, 740 patients (371 in SUR, 369 in RFA) were enrolled from 49 participating hospitals in Japan. The SUR group had significantly fewer patients with chronic hepatitis C (56.6% vs. 69.4%), higher median value of platelet count (145 vs. 120 × 109/L), and more patients with > 2 cm tumors (49.9% vs. 27.9%); most patients had a single tumor (91.1% vs. 88.3%). During the median follow-up period of 5 years, tumor recurrence was observed in 192 of SUR and 218 of RFA with 3-year RFS being 66.0% and 61.7%, respectively ( P = 0.091). In subgroup analysis, RFS was significantly better in SUR in patients with ≤ 2 cm tumors (62.9% vs. 51.7% in 3 years; hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.56-0.93; P = 0.014), whereas the difference was not significant in those with > 2 cm tumors (52.7% vs. 46.4%; HR 0.85, 95% CI 0.63-1.18; P = 0.34). The adjusted HR for RFS using inversed probability of treatment weighting was 0.89 (95% CI, 0.72-1.10; P = 0.287). Conclusions: The imbalance in patient characteristics reflected a real-world practice. Factors related to background liver disease rather than tumor characteristics might have a larger impact on the recurrence in early HCC. Clinical trial information: C000001796 .

scholarly journals Liquid Biopsy of Hepatocellular Carcinoma: Circulating Tumor-Derived Biomarkers

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Chang-Qing Yin ◽  
Chun-Hui Yuan ◽  
Zhen Qu ◽  
Qing Guan ◽  
Hao Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Liquid Biopsy ◽  
Clinical Decision Making ◽  
Early Stage ◽  
Prognostic Significance ◽  
Liquid Biopsies ◽  
Tumor Biopsy ◽  
Diagnostic Strategies ◽  
Systemic Treatments

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide due to latent liver disease, late diagnosis, and nonresponse to systemic treatments. Till now, surgical and/or biopsy specimens are still generally used as a gold standard by the clinicians for clinical decision-making. However, apart from their invasive characteristics, tumor biopsy only mirrors a single spot of the tumor, failing to reflect current cancer dynamics and progression. Therefore, it is imperative to develop new diagnostic strategies with significant effectiveness and reliability to monitor high-risk populations and detect HCC at an early stage. In the past decade, the potent utilities of “liquid biopsy” have attracted intense concern and were developed to evaluate cancer progression in several clinical trials. “Liquid biopsies” represent a series of noninvasive tests that detect cancer byproducts easily accessible in peripheral blood, mainly including circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) that are shed into the blood from the tumor sites. In this review, we focus on the recent developments in the field of “liquid biopsy” as well as the diagnostic and prognostic significance of CTCs and cfNAs in HCC patients.

scholarly journals Autoantibody to GNAS in Early Detection of Hepatocellular Carcinoma: A Large-Scale Sample Study Combined with Verification in Serial Sera from HCC Patients

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 97
Author(s):  
Xiao Wang ◽  
Keyan Wang ◽  
Cuipeng Qiu ◽  
Bofei Wang ◽  
Xiaojun Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Detection ◽  
Large Scale ◽  
Early Stage ◽  
Decompensated Cirrhosis ◽  
Compensated Cirrhosis ◽  
Autoantibody Response ◽  
Potential Biomarker ◽  
Early Hcc ◽  
Normal Controls

The aim of this study was to explore the value of autoantibody to GNAS in the early detection of hepatocellular carcinoma (HCC). In a large-scale sample set of 912 participants (228 cases in each of HCC, liver cirrhosis (LC), chronic hepatitis B (CHB), and normal controls (NCs) groups), autoantibody to GNAS was detected with a positive result in 47.8% of HCC patients, which was significantly higher than that in patients with LC (35.1%), CHB (19.7%), and NCs (19.7%). Further analysis showed that the frequency of autoantibody to GNAS started increasing in compensated cirrhosis patients (37.0%) with a jump in decompensated cirrhosis patients (53.2%) and reached a peak in early HCC patients (62.4%). The increasing autoantibody response to GNAS in patients at different stages was closely associated with the progression of chronic liver lesions. The result from 44 human serial sera demonstrated that 5 of 11 (45.5%) HCC patients had elevated autoantibody to GNAS before and/or at diagnosis of HCC. Moreover, 46.1% and 62.4% of high positive rates in alpha-fetoprotein (AFP) negative and early-stage HCC patients can supplement AFP in early detection of HCC. These findings suggest that autoantibody to GNAS could be used as a potential biomarker for the early detection of HCC.

scholarly journals Manuscript Impact on Prognosis of Different Anatomical Hepatectomy Approaches for Single Hepatocellular Carcinoma in Segment VI

2019 ◽  
Author(s):  
Jie Mei ◽  
Shao-Hua Li ◽  
Qiao-Xuan Wang ◽  
Liang-He Lu ◽  
Anna Kan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Stage ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Postoperative Recovery ◽  
Free Survival ◽  
Propensity Score Matching Analysis ◽  
Early Hcc ◽  
The Common ◽  
Preoperative Factors

Abstract Background. Liver resection is effective for hepatocellular carcinoma (HCC). For a single HCC in subsegment 6 (S6), segmentectomy of S6, S5 (S6+5) and segmentectomy of S6, S7 (S6+7) are the common anatomical surgical procedures. However, the benefit of the two resection methods has not been clarified in this patient subgroup. This study aimed to compare the outcomes of S6+5 resection and S6+7 resection for single, early HCC located on S6 of the liver. Methods. In total, 115 patients with single HCC in S6 without vascular invasion and distant metastasis were included in this study. The patients were divided into the S6+5 group (n=73) and S6+7 group (n=42). A one-to-one propensity score-matching analysis (PSM) was performed to minimize the effect of potential confounders. Results. Forty patients from each group were matched. The preoperative factors were balanced between the two groups. The 1-, 2-, and 3-year overall survival (OS) rates in the S6+5 group were 92.3%, 82.1%, and 76.8%, respectively, and in the S6+7 group were 94.5%, 91.6% and 88.6%, respectively (p=0.197). The 1-, 2-, and 3-year recurrence-free survival (RFS) rates in the S6+5 group were 71.9%, 61.6%, and 58.9%, respectively, and in the S6+7 group were 83.5%, 77.7% and 68.8%, respectively (p=0.432). There were no significant differences in the recurrence pattern and postoperative recovery of liver function. The surgical procedure was not a significant risk factor for the OS and RFS in both the uni- and multivariate analyses. Conclusion. S6+5 and S6+7 resection achieved similar outcomes for early-stage solitary HCC in S6.

MicroRNA-30e and MicroRNA-223 Expression for Early Diagnosis of Hepatocellular Carcinoma Associated with Hepatitis C Virus

2020 ◽  
Vol 3 (1) ◽  
pp. 97-104
Author(s):  
Amany Ragab Youssef ◽  
Samah Bastawy ◽  
Karim Montasser ◽  
Sally Abed ◽  
Muhammad Diasty ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Early Diagnosis ◽  
Early Stage ◽  
Control Subjects ◽  
Combined Use ◽  
Significant Difference ◽  
Early Hcc ◽  
Healthy Control

Background. The goals of this study were to elucidate the use of the expression of microRNA-30e (miR-30e) and microRNA-223 (miR-223) as diagnostic biomarkers for early diagnosis of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection. Methods. The study included three groups, the first group included thirty patients with HCC associated with HCV, the second group included thirty patients with cirrhosis with HCV and the third group included thirty healthy control subjects. Blood samples were obtained for determination of serum expression of miR-30e and miR-223 by real time polymerase chain reaction. Results. There was significant decrease of miR-30e of expression in patients with HCC (0.16 ± 0.1) compared to both patients with cirrhosis (0.4 ± 0.2, P<0.01) and healthy control subjects (1.2 ± 0.4, P<0.001). There was also significant reduction of miR-223 expression levels in patients with HCC (0.2 ± 0.1) compared to patients with cirrhosis (0.5 ± 0.2, P<0.01) and healthy control subjects (1.0 ± 0.1, P<0.001). There was also significant decrease of miR-30e expression in late stage versus early stage of HCC (0.1 ± 0.0 vs. 0.22 ± 0.1, P<0.001), while there was no significant difference of alpha-fetoprotein (AFP) between patients with late and early HCC. Also, values of miR-223 had significantly reduced levels in late HCC compared to its expression values in early HCC (0.1± 0.0 vs. 0.23 ± 0.2, P<001). Conclusion. There was significant reduction of expression of miR-30e and miR-223 in serum of HCC patients compared to either patients with cirrhosis or healthy subjects. These results show that the combined use of both biomarkers had better sensitivity in the diagnosis of HCC compared to AFP.

scholarly journals Applying NGS Data to Find Evolutionary Network Biomarkers from the Early and Late Stages of Hepatocellular Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-27 ◽  
Author(s):  
Yung-Hao Wong ◽  
Chia-Chou Wu ◽  
Chih-Lung Lin ◽  
Ting-Shou Chen ◽  
Tzu-Hao Chang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systems Biology ◽  
Liver Cancer ◽  
Late Stage ◽  
Early Stage ◽  
Network Structures ◽  
Network Biomarkers ◽  
Two Stages ◽  
Ngs Data ◽  
Late Stages

Hepatocellular carcinoma (HCC) is a major liver tumor (~80%), besides hepatoblastomas, angiosarcomas, and cholangiocarcinomas. In this study, we used a systems biology approach to construct protein-protein interaction networks (PPINs) for early-stage and late-stage liver cancer. By comparing the networks of these two stages, we found that the two networks showed some common mechanisms and some significantly different mechanisms. To obtain differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two stages of liver cancer by systems biology method using NGS data from cancer cells and adjacent noncancer cells. Using carcinogenesis relevance values (CRVs), we identified 43 and 80 significant proteins and their PPINs (network markers) for early-stage and late-stage liver cancer. To investigate the evolution of network biomarkers in the carcinogenesis process, a primary pathway analysis showed that common pathways of the early and late stages were those related to ordinary cancer mechanisms. A pathway specific to the early stage was the mismatch repair pathway, while pathways specific to the late stage were the spliceosome pathway, lysine degradation pathway, and progesterone-mediated oocyte maturation pathway. This study provides a new direction for cancer-targeted therapies at different stages.

scholarly journals Evaluating the diagnostic value of serum Des-γ carboxy prothrombin in the detection of hepatocellular carcinoma

2021 ◽  
Vol 63 (9) ◽  
pp. 33-38
Author(s):  
Dang Quan Nguyen ◽  
◽  
Thi Thanh Thao Nguyen ◽  
Nguyen Thanh Thuy Pham ◽  
Thi Thuy Hang Le ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Sensitivity And Specificity ◽  
Diagnostic Value ◽  
Serum Marker ◽  
Serum Markers ◽  
Roc Curve Analysis ◽  
Early Hcc ◽  
High Risk Populations ◽  
Effect Of Treatment ◽  
C 50

Hepatocellular carcinoma (HCC) is amongst the most common cancers in the world and Vietnam. Most HCC patients are diagnosed late, so the effect of treatment is limited. Hence, early diagnosis for high-risk populations using medical imaging and serum markers is very important to control HCC. Recently, α-fetoprotein (AFP) has been popularly used as a serum marker for screening of HCC. Unfortunately, AFP is not trustworthy enough for HCC diagnosis, especially early HCC. Therefore, this study was deployed to estimate the ability of serum Des-γ carboxy prothrombin (DCP) applied in the diagnosis of HCC. DCP and AFP concentration in serum of 50 early HCC patients (stage A), 50 late HCC patients (stage B and C), 50 HBV/HCV-infected patients, and 50 healthy persons were identified. ROC curve analysis manifested that with the cut-off value at 11.93 ng/ml, DCP allowed identifying HCC cases with the sensitivity and specificity of 50 and 94%, respectively. With early HCC, the sensitivity of DCP decreased to 34%, while the specificity was unchanged. In the case of AFP, results showed that the sensitivity and specificity of this marker for HCC were 39 and 95%, with the cut-off value at 952.1 ng/ml. For early HCC, it was impossible to use AFP for diagnosis. The combination of DCP and AFP serum markers in the detection of HCC did not improve the sensitivity of the diagnosis compared to that of DCP alone. The study demonstrated that serum biomarker DCP can be used instead of AFP in the diagnosis of HCC, which improves the diagnostic sensitivity

scholarly journals Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy

2019 ◽  
Vol 116 (13) ◽  
pp. 6308-6312 ◽  
Author(s):  
Chunfeng Qu ◽  
Yuting Wang ◽  
Pei Wang ◽  
Kun Chen ◽  
Minjie Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liquid Biopsy ◽  
Early Stage ◽  
Elevated Serum ◽  
Normal Liver ◽  
Protein Markers ◽  
Liquid Biopsies ◽  
B Virus ◽  
Asymptomatic Individuals

Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6–8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same timescale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.

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