Virus induced hepatocellular carcinoma (HCC) and protein biomarkers

Author(s):  
Hamza Abbas Jaffari ◽  
Sumaira Mazhar

Hepatocellular carcinoma (HCC) is a standout amongst the most widely recognized cancers around the world, and just as the alcoholic liver disease it is also progressed by extreme viral hepatitis B or C. At the early stage of the disease, numerous patients are asymptomatic consequently late diagnosis of HCC occurs resulting in expensive surgical resection or transplantation. On the basis of the alpha fetoprotein (AFP) estimation, combined with the ultrasound and other sensitive imaging techniques used, the non-invasive detection systems are available. For early disease diagnosis and its use in the effective treatment of HCC patients, the identification of HCC biomarkers has provided a breakthrough utilizing the molecular genetics and proteomics. In the current article, most recent reports on the protein biomarkers of HBV or HCV-related HCC and their co-evolutionary association with liver cancer are reviewed.

2020 ◽  
Author(s):  
Amy K Kim ◽  
James P. Hamilton ◽  
Selena Y. Lin ◽  
Ting-Tsung Chang ◽  
Hie-Won Hann ◽  
...  

ABSTRACTBackground & AimsContinued limitations in hepatocellular carcinoma (HCC) screening have led to late diagnosis with poor survival, despite well-defined high-risk patient populations. Our aim is to develop a non-invasive urine circulating tumor DNA (ctDNA) biomarker panel for HCC screening to aid in early detection.MethodsCandidate ctDNA biomarkers was prescreened in urine samples obtained from HCC, cirrhosis, and hepatitis patients. Then, 609 patient urine samples with HCC, cirrhosis, or chronic hepatitis B were collected from five academic medical centers and evaluated by serum alpha feto-protein (AFP) and urine ctDNA panel using logistic regression, a Two-Step machine learning algorithm, and iterated 10-fold cross-validation.ResultsMutated TP53, and methylated RASSF1a and GSTP1, were selected for the urine ctDNA panel. The sensitivity of AFP-alone (9.8 ng/mL cut-off) to detect HCC was 71% by Two-Step. The combination of ctDNA and AFP increased the sensitivity to 81% at a specificity of 90%. The AUROC for the combination of ctDNA and AFP vs. AFP-alone were 0.925 (95% CI, 0.924-0.925) and 0.877 (95% CI, 0.876-0.877), respectively. Notably, among the patients with AFP <20 ng/mL, the combination panel correctly identified 64% of HCC cases. The panel performed superiorly to AFP-alone in early-stage HCC (BCLC A) with 80% sensitivity and 90% specificity. In an iterated 10-fold cross-validation analysis, the AUROC for the combination panel was 0.898 (95% CI, 0.895-0.901).ConclusionsThe combination of urine ctDNA and serum AFP can increase HCC detection rates including in those patients with low-AFP. Given the ease of collection, a urine ctDNA panel could be a potential non-invasive HCC screening test.


Micromachines ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 11
Author(s):  
Leilei Shi ◽  
Leyla Esfandiari

Electrical Impedance Spectroscopy (EIS) has been widely used as a label-free and rapid characterization method for the analysis of cells in clinical research. However, the related work on exosomes (40–150 nm) and the particles of similar size has not yet been reported. In this study, we developed a new Lab-on-a-Chip (LOC) device to rapidly entrap a cluster of sub-micron particles, including polystyrene beads, liposomes, and small extracellular vesicles (exosomes), utilizing an insulator-based dielectrophoresis (iDEP) scheme followed by measuring their impedance utilizing an integrated electrical impedance sensor. This technique provides a label-free, fast, and non-invasive tool for the detection of bionanoparticles based on their unique dielectric properties. In the future, this device could potentially be applied to the characterization of pathogenic exosomes and viruses of similar size, and thus, be evolved as a powerful tool for early disease diagnosis and prognosis.


2021 ◽  
Vol 10 (2) ◽  
pp. 353
Author(s):  
Pierre Nahon ◽  
Erwan Vo Quang ◽  
Nathalie Ganne-Carrié

Hepatocellular carcinoma (HCC) incidence has dramatically decreased in patients infected with HCV and HBV due to the widespread use of highly effective antiviral agents. Nevertheless, a substantial proportion of patients with advanced fibrosis or cirrhosis following HCV clearance of in case of HBV control whatever the stage of fibrosis remains at risk of liver cancer development. Cancer predictors in these virus-free patients include routine parameters estimating coexisting comorbidities, persisting liver inflammation or function impairment, and results of non-invasive tests which can be easily combined into HCC risk scoring systems. The latter enables stratification according to various liver cancer incidences and allocation of patients into low, intermediate or high HCC risk probability groups. All international guidelines endorse lifelong surveillance of these patients using semi-annual ultrasound, with known sensibility issues. Refining HCC prediction in this growing population ultimately will trigger personalized management using more effective surveillance tools such as contrast-enhanced imaging techniques or circulating biomarkers while taking into account cost-effectiveness parameters.


The Analyst ◽  
2020 ◽  
Vol 145 (23) ◽  
pp. 7623-7629 ◽  
Author(s):  
Sara Mosca ◽  
Priyanka Dey ◽  
Marzieh Salimi ◽  
Francesca Palombo ◽  
Nick Stone ◽  
...  

Spatially Offset Raman Spectroscopy (SORS) allows chemical characterisation of biological tissues at depths enabling in vivo localization of biomarkers for early disease diagnosis.


2014 ◽  
Vol 2014 ◽  
pp. 1-25 ◽  
Author(s):  
A. Kornberg

The implementation of the Milan criteria (MC) in 1996 has dramatically improved prognosis after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Liver transplantation has, thereby, become the standard therapy for patients with “early-stage” HCC on liver cirrhosis. The MC were consequently adopted by United Network of Organ Sharing (UNOS) and Eurotransplant for prioritization of patients with HCC. Recent advancements in the knowledge about tumor biology, radiographic imaging techniques, locoregional interventional treatments, and immunosuppressive medications have raised a critical discussion, if the MC might be too restrictive and unjustified keeping away many patients from potentially curative LT. Numerous transplant groups have, therefore, increasingly focussed on a stepwise expansion of selection criteria, mainly based on tumor macromorphology, such as size and number of HCC nodules. Against the background of a dramatic shortage of donor organs, however, simple expansion of tumor macromorphology may not be appropriate to create a safe extended criteria system. In contrast, rather the implementation of reliable prognostic parameters of tumor biology into selection process prior to LT is mandatory. Furthermore, a multidisciplinary approach of pre-, peri-, and posttransplant modulating of the tumor and/or the patient has to be established for improving prognosis in this special subset of patients.


2018 ◽  
pp. 70-76
Author(s):  
V.T. Kirienko ◽  
◽  
I. A. Zaytsev ◽  
V.V. Grushkevich ◽  
V.V. Potii ◽  
...  

Presents the risk factors for the development of hepatocellular carcinoma, the current possibilities for screening and early diagnosis of HCC with imaging techniques, non-invasive serological markers. The categories of patients subject to HCC screening and the examination algorithm are determined. Key words: hepatocellular carcinoma, primary liver cancer, screening, early diagnosis.


2021 ◽  
Vol 11 ◽  
Author(s):  
Alice Faversani ◽  
Chiara Favero ◽  
Laura Dioni ◽  
Angela Cecilia Pesatori ◽  
Valentina Bollati ◽  
...  

BackgroundDespite significant improvement in screening programs for cancers of the respiratory district, especially in at-risk subjects, early disease detection is still a major issue. In this scenario, new molecular and non-invasive biomarkers are needed to improve early disease diagnosis.MethodsWe profiled the miRNome in exhaled breath condensate (EBC) and plasma samples from fourteen patients affected by lung AdCa, nine healthy subjects. miRNA signatures were then analyzed in another neoplasia of the respiratory district, i.e. pleural mesothelioma (n = 23) and subjects previously exposed to asbestos were used as controls for this cohort (n = 19). Selected miRNAs were analyzed in purified pulmonary neoplastic or normal epithelial and stromal cell subpopulation from AdCa patients. Finally, the plasmatic miRNA signature was analyzed in a publicly available cohort of NSCLC patients for data validation and in silico analysis was performed with predicted miRNA targets using the multiMiR tool and STRING database.ResultsmiR-597-5p and miR-1260a are significantly over-expressed in EBC from lung AdCa and are associated with AdCa. Similarly, miR-1260a is also up-regulated in the plasma of AdCa patients together with miR-518f-3p and correlates with presence of lung cancer, whereas let-7f-5p is under-expressed. Analysis of these circulating miRNAs in pleural mesothelioma cases confirmed that up-regulation of miR-518f-3p, -597-5p and -1260a, is specific for lung AdCa. Lastly, quantification of the miRNAs in laser-assisted microdissected lung tissues revealed that miR-518f-3p, 597-5p and miR-1260a are predominantly expressed in tumor epithelial cells. Validation analysis confirmed miR-518f-3p as a possible circulating biomarker of NSCLC. In silico analysis of the potentially modulated biological processes by these three miRNAs, shows that tumor bioenergetics are the most affected pathways.ConclusionsOverall, our data suggest a 3-miRNAs signature as a non-invasive and accurate biomarker of lung AdCa. This approach could supplement the current screening approaches for early lung cancer diagnosis.


2020 ◽  
Vol 13 ◽  
pp. 175628482093173
Author(s):  
Boris J. B. Beudeker ◽  
Andre Boonstra

Hepatocellular carcinoma (HCC) is estimated to be the fourth leading cause of cancer-related deaths worldwide. HCC patients face a dismal prognosis because symptoms usually appear in an advanced stage of disease. The detection of early stage HCC allows for curative surgical treatment and therefore saves lives. Specific non-invasive or diagnostic markers for HCC may represent a valuable tool for detecting these tumors at an early stage. The clinically most established serological biomarker alpha-fetoprotein shows only limited diagnostic performance, however novel candidate biomarkers and biomarker panels for detecting HCC at early stages of development are being studied. In this review we will discuss the findings of these studies.


Author(s):  
Carmen García-Alba

This study is part of a larger research study (doctoral dissertation), in which a comparative study with adolescent samples is done: 50 anorexic restricting patients (ANP), 50 patients diagnosed with depression (DP) and 50 non patients (NP). The proposed objective is two-fold: 1) To try to clarify the existing relationship between Anorexia (AN) and Depression (D), investigated from diverse disciplines but without conclusive results. 2) To detect in the ANP personality different traits from those of other groups, which should, if possible, allow to detect them at an early stage for an adequate prognosis. The current article presents the Rorschach findings in relation to the cognitive functioning of the ANP. In them, the following has been detected: (1) An information processing similar to that of the other groups, even with a more complete (L ≤ .99), more complex (DQ+↑) and better discriminated (Zd↑) grasp of the stimulus; (2) Mediating processes very similar to those of the other groups, sharing with them the perceptive maladjustments (X–%↑) and an excessive individualism (Xu%↑); (3) A clearly differentiating ideation disorder. Definitely, the ANP use predominantly ideation (M↑), but their thought, usually well-adjusted (MQo↑), presents eventual operations of delusional type (MQnone↑). Above that, their thinking is marked by a great passivity (Mp↑), which makes them more vulnerable to accept ideas without criticizing them and it results in a very inefficient thinking, which spins around these concepts without finding solutions, entering into a sort of ruminating which is completely unproductive. The differences toward the obsessive pathology are established. The discriminant analysis conducted with all the Rorschach variables that resulted as significant throughout the research, provides quite a consistent function which discriminates the ANP: MQnone↑, Mp↑, FD↓, Ma↑, MQo↑, AdjD↑, Sum H↑, (H)↑. Based on this we can understand that these adolescents, being in a developmental period of big changes and disorientations in relation with their own image, confronted with life events, and possibly starting off with some biologic vulnerability: (1) Due to the alterations of their ideation, accept without criticism (Mp) irrational ideas dominating in our culture, in which slimness appears as the only model, synthesis of intelligence, beauty and success; remaining captured in this type of mental activity (MQnone), which they cannot escape nor criticize (Mp), despite they reason adequately on other topics (MQo); (2) Their alterations of self-perception [(H)] make them hide themselves in a fantasized image, which is the axis of their interests and the only thing that really matters to them; (3) The resources they have to decide on behaviors and to finish these deliberately (AdjD), and their scarce tendency to the introspection (FD) lead to their decision of not eating, based on distorted and passively accepted thinking, which has great power and thus, so difficult to modify. Finally, based on the Rorschach data obtained, the hypothesis of a personality disorder as underlying pathology is pointed out.


Sign in / Sign up

Export Citation Format

Share Document