Molecular diagnosis of hepatocellular carcinoma: trends in biomarkers combination to enhance early cancer detection

Chia, Tiong Sun; Wong, Kwong Fai; Luk, John M.

doi:10.20517/2394-5079.2018.112

Cited by 5 publications

(6 citation statements)

References 129 publications

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“…Data of the present work also showed that PI3K was overexpressed in all experimental HCC stages as compared to the control group which is compatible with the previously reported findings indicated that PI3K was upregulated and implicated in HCC progression. 7,27,28 Furthermore, both intermediate and late stages exhibited a significant increase in PI3K content compared to…”

Section: Discussionmentioning

confidence: 96%

“…However many studies investigated the diagnostic performance of various protein biomarkers at early stages of HCC 5 . There is an imperative necessity to investigate novel diagnostic biomarkers for HCC at an early stage that correlate with the tumor stage, and allow better evaluation of therapeutic efficacy 6,7 …”

Section: Introductionmentioning

confidence: 99%

“…5 There is an imperative necessity to investigate novel diagnostic biomarkers for HCC at an early stage that correlate with the tumor stage, and allow better evaluation of therapeutic efficacy. 6,7 Tuftelin 1 (TUFT1) is an enamel associated teeth protein deemed to play a role in enamel mineralization. As well as, TUFT1 is expressed in embryonic stem cells, neuronal cells, and other non-mineralizing tissues like brain, eyes, lung, adrenal gland, liver, kidneys, testes, and tumor tissues.…”

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confidence: 99%

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The expression of tuftelin 1 as a new theranostic marker in early diagnosis and as a therapeutic target in hepatocellular carcinoma

Abdel-Hamid

Zakaria

Ansary

et al. 2023

Cell Biochemistry & Function

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Currently, many challenges are associated with hepatocellular carcinoma (HCC) as the failure of early diagnosis, and the lack of effective therapy. This study aimed to investigate the possible role of tuftelin 1 (TUFT 1) in the early diagnosis of HCC and evaluate the potential contribution of the TUFT 1/Ca+2/phosphinositol 3 kinase (PI3K) pathway in dantrolene sodium (Dan) therapeutic outcomes. The study was performed on two sets of rats, the staging (30 rats) and treatment sets (80 rats). HCC was induced by a single dose of diethylnitrosamine (DENA). The hepatic content of TUFT 1 protein was assayed via western blot and immunohistochemistry (IHC), while PI3K, vascular endothelial growth factor (VEGF), Cyclin D1, and matrix‐metalloproteinase‐9 (MMP‐9) contents were assessed using enzyme‐linked immunosorbent assay. Hepatic and serum calcium were measured colorimetrically. Furthermore, the nuclear proliferation marker, (Ki‐67), (Kiel [Ki] where the antibody was produced in the University Department of Pathology and the original clone number is 67)—expression was assessed by IHC. TUFT 1/Ca+2/PI3K signaling pathway was progressively activated in the 3 studied stages of HCC with subsequent upregulation of angiogenesis, cell cycle, and metastasis. More interestingly, Dan led to TUFT 1/Ca+2/PI3K pathway disruption by diminution of the hepatic contents of TUFT 1, calcium, PI3K, VEGF, Cyclin D1, and MMP‐9 in a dose‐dependent pattern. TUFT 1 can serve as a theranostic biomarker in HCC. Moreover, Dan exerted an antineoplastic effect against HCC via the interruption of TUFT 1/Ca+2/PI3K pathway.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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The expression of tuftelin 1 as a new theranostic marker in early diagnosis and as a therapeutic target in hepatocellular carcinoma

Abdel-Hamid

Zakaria

Ansary

et al. 2023

Cell Biochemistry & Function

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“…Various studies have suggested biomarkers for liver cancer, and the effort to identify additional markers is ongoing ( 40 ). Numerous methods, including immunohistochemistry, ELISA and western blotting, have previously been used in such studies ( 41 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

HMBS is the most suitable reference gene for RT‑qPCR in human HCC tissues and blood samples

et al. 2021

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Reverse transcription-quantitative (RT-q) PCR is the most feasible and useful technique for identifying and evaluating cancer biomarkers; however, the method requires suitable reference genes for gene expression analysis. The aim of the present study was to identify the most suitable reference gene for the normalization of relative gene expression in human hepatocellular carcinoma (HCC) tissue and blood samples. First, 14 candidate reference genes were selected through a systematic literature search. The expression levels of these genes ( ACTB, B2M, GAPDH, GUSB, HMBS, HPRT1, PGK1, PPIA, RPLP0, RPL13A, SDHA, TBP, TFRC and YWHAZ ) were evaluated using human multistage HCC transcriptome data (dataset GSE114564), which included normal liver (n=15), chronic hepatitis (n=20), liver cirrhosis (n=10), and early (n=18) and advanced HCC (n=45). From the 14 selected genes, five genes, whose expression levels were stable in all liver disease statuses ( ACTB, GAPDH, HMBS, PPIA and RPLP0 ), were further assessed using RT-qPCR in 40 tissues (20 paired healthy tissues and 20 tissues from patients with HCC) and 40 blood samples (20 healthy controls and 20 samples from patients with HCC). BestKeeper statistical algorithms were used to identify the most stable reference genes, of which HMBS was found to be the most stable in both HCC tissues and blood samples. Therefore, the results of the present study suggest HMBS as a promising reference gene for the normalization of relative RT-qPCR techniques in HCC-related studies.

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“…HCC can be diagnosed with laboratory tests and radiology methods such as ultrasonography, triphasic computerized tomography (triphasic CT-scan), and dynamic magnetic resonance imaging (dynamic MRI) [6].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Plasma Vitronectin as Diagnostic and Prognostic Marker of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Cirrhosis

Mohamed

Esmaiel

Shabana

et al. 2022

Gastroenterology Insights

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Background: hepatitis C is an inflammatory liver disease caused by the hepatitis C infection (HCV), and without treatment, almost 50% will progress to liver cirrhosis. Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and the fourth leading cause of cancer-related mortality. Aim of the study: the objective of this study was to evaluate the serum level of vitronectin (VTN) compared to AFP and determine their role as diagnostic and prognostic markers of HCV-related liver diseases. Subject and Methods: this study involved 52 HCV patients from which 26 patients were cirrhotic, and 26 patients had HCC (on top of hepatitis C virus-related cirrhosis) plus 10 healthy people as a control group. It was carried out in Gastroenterology and Hepatology Unit, Internal Medicine Department, Zagazig University Hospitals, Egypt. All individuals in this study were subjected to physical examination, full history taking, liver function tests, assessment of serum levels of Vitronectin (VTN) and alpha-fetoprotein (AFP) before and after the intervention within three months. Results: serum level of vitronectin increased significantly in cirrhosis patients and HCC patients than controls (p = 0.0041), (p < 0.001), respectively, and in HCC than cirrhosis patients (p < 0.001). Significant positive correlations were observed between levels of serum VTN and AFP in all HCV patients as well as cirrhotic patients (p < 0.001, p = 0.011, respectively). On the contrary, VTN and AFP didn’t show a significant correlation in HCC patients’ group. Moreover, the median serum level of VTN decreased significantly after treatment in patients with HCC (p < 0.001). At cut-off 38.5 ng/mL for AFP it shows sensitivity 80.8%, specificity 76.9% to differentiate HCC from cirrhosis cases. While VTN shows 84.6% sensitivity, 96.2% specificity at cut-off 26.5 μg/mL. Regarding clinicopathological characteristics and VTN levels, half of patients were stage B, 63.9% had tumor size >3 cm, 84.6% had more than one focal lesion. Conclusions: these results may allow one to speculate a potential role of Vitronectin in diagnosis and prognosis of HCC on top of cirrhosis related to HCV infection in addition to AFP and US and CT.

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Molecular diagnosis of hepatocellular carcinoma: trends in biomarkers combination to enhance early cancer detection

Cited by 5 publications

References 129 publications

The expression of tuftelin 1 as a new theranostic marker in early diagnosis and as a therapeutic target in hepatocellular carcinoma

The expression of tuftelin 1 as a new theranostic marker in early diagnosis and as a therapeutic target in hepatocellular carcinoma

HMBS is the most suitable reference gene for RT‑qPCR in human HCC tissues and blood samples

Assessment of Plasma Vitronectin as Diagnostic and Prognostic Marker of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Cirrhosis

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