Caspase-Cleaved Cytokeratin 18 Fragment M30 as a Potential Biomarker of Macrovascular Invasion in Hepatocellular Carcinoma

Elalfy, Hatem; Besheer, Tarek; Arafa, Mostafa A.; El-Hussiny, Mona Abo-Bakr; Latif, Mahmoud Abd El; Alsayed, Sahar Alsayed Mohamed

doi:10.1007/s12029-017-9937-6

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…4a shows, only CK18, GPC3, and OPN were expressed at a significantly higher level in the no antiviral HCC group compared to the antiviral group. It has been reported that the up-regulation of CK18, GPC3, and OPN are associated with increased tumor aggressiveness and poor prognosis 19,23–25 . Then, the IHC scoring was performed by adding the values of the intensity and relative abundance (Materials and Methods), and the average score of such proteins in each group was calculated.…”

Section: Resultsmentioning

confidence: 99%

Precancer antiviral treatment reduces microvascular invasion of early-stage Hepatitis B-related hepatocellular carcinoma

Duan

Liu

Yang

et al. 2019

Sci Rep

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The impact of antiviral therapy before tumorigenesis on microvascular invasion (MVI) of Chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is still unknown. In this retrospective cohort study 3,276 HCC patients with early-stage who underwent curative resection were included. We investigated the effect of precancer antiviral therapy on the pathology, especially MVI, of CHB-related HCC. MVI occurrence rates of CHB-related HCC stratified by histopathologic inflammation grades of G1, G2, and G3 were 30.4%, 34.7%, and 38.6%, respectively, compared to 19.8% for CHB-negative HCC. Patients who received standard antiviral treatment showed much lower rates of MVI, higher tumor capsule integrity, less frequent satellite micronodules and lower AFP level compared to the no antiviral group. Moreover, precancer antiviral therapy prolonged the disease-free survival (DFS), which are also proved to be independent indicators of DFS. In addition, we show that antivirals may suppress early progression of HCC primarily by inhibition of HBV viral load, and influencing the expression levels of CK18, GPC3, OPN and pERK. Hence, we demonstrate that precancer antivirals significantly reduce the MVI rate of CHB-related HCC, reduce malignancy of early-stage HCC, and improve HCC prognosis. Thus, this study confirms the importance of antiviral therapy for CHB patients.

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Section: Resultsmentioning

confidence: 99%

Precancer antiviral treatment reduces microvascular invasion of early-stage Hepatitis B-related hepatocellular carcinoma

Duan

Liu

Yang

et al. 2019

Sci Rep

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“…Recent studies have shown that elevated M30 CK-18 concentrations may be a useful marker for early stages HCC. Elalfy et al calculated a ROC curve for the M30 CK-18 to discriminate between macrovascular invasions of HCC, which has shown 100% sensitivity and 98% specificity for a cutoff of 304.5 ng/mL (AUC: 0.997, P < 0.001) [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Serum Cytokeratin 18 M30 Levels in Chronic Hepatitis B Reflect Both Phase and Histological Activities of Disease

Świderska

Jaroszewicz

Parfieniuk‐Kowerda

et al. 2017

Mediators of Inflammation

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Chronic hepatitis B has highly a dynamic course with significant fluctuations of HBV-DNA and ALT impeding assessment of disease activity. New biomarkers of inflammatory versus noninflammatory stages of HBV infection are urgently needed. Cytokeratin 18 epitope M30 (M30 CK-18) is a sensitive marker of cell death. We aimed to investigate an association between serum M30 CK-18 and histological activity and phase of HBV infection. 150 Caucasian patients with HBV-infection were included in the study. Serum M30 CK-18 levels reflected phase of disease, being significantly higher in both HBeAg(+) and HBeAg(−) hepatitis B in comparison to HBsAg(+) carrier groups. The highest serum M30 CK-18 levels were observed in subjects with the most advanced stages of HBV. Moreover, its serum concentrations correlated with both inflammatory activity and fibrosis advancement (ANOVA P < 0.001). Importantly, serum M30 CK-18 levels were able to discriminate patients with mild versus moderate-advanced fibrosis (AUC: 0.86) and mild versus active liver inflammation (AUC: 0.79). M30 CK-18 serum concentration has good sensitivity and specificity in discriminating mild versus moderate/severe fibrosis and inflammation even in patients with normal ALT activity. This study suggests M30 CK-18 as a potential noninvasive marker of disease activity and also a marker of phase of persistent HBV infection.

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“…8 (72.7 %) of the studies provided data of M30 expression, and 8 (72.7%) of the studies provided data of M65 expression, while 5 (45.5 %) of them provided data of both. Four (36.4 %) of the studies were in gastric cancer [18][19][20][21], two (18.2 %) studies in HCC [22,23], three (27.3 %) studies in colorectal cancer [24][25][26], and two (18.2 %) in pancreatic cancer [27,28]. The cut-off value of M30 and M65 varies in different studies, ranging from 59.1 U/L to 887 U/L, and from 199.3 U/L to1614 U/L, respectively.…”

Section: Literature Detailsmentioning

confidence: 99%

Prognostic value of non-invasive serum Cytokeratin 18 detection in gastrointestinal cancer: a meta-analysis

et al. 2019

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Background: Gastrointestinal cancer is one of the most common neoplasms. Cytokeratin 18(CK18) is widely expressed in many different organs and cancers. Emerging data suggested conflicting results about the role of CK18 during carcinogenesis. The aim of this study is to systematically review the prognostic value of circulating CK18 (M65) and caspase-Cleaved CK18 (M30) in digestive cancers. Materials and Methods: We searched major database for manuscripts reporting the effect of pretreatment CK18 on survival of digestive cancer patients. Revman5.3 and R were the software used for analysis. Pooled multivariable-adjusted hazard ratios (HR) for overall survival (OS) were calculated in all patients and many different subgroup analyses by stratifying on tumor type, metastasis stage, and ethnicity. Results: 11 original studies were included for analysis. A low level of M30 and M65 were shown to be a protective factor for all cancer patients (HR 0.49, 95%CI 0.33-0.73, P=0.0003; HR 0.48, 95% CI 0.32-0.70, P =0.0001, respectively). The low M30 remained to be a protective factor for metastasized cancer patients while M65 had no statistically significant correlation with prognosis. Conclusions: Non-invasive total and cleaved CK18 level detection by ELISA could be potentially a useful predictor of prognosis of digestive cancer patients. Further studies are warranted to investigate the molecular mechanisms of CK18.

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Caspase-Cleaved Cytokeratin 18 Fragment M30 as a Potential Biomarker of Macrovascular Invasion in Hepatocellular Carcinoma

Abstract: The present study suggests that increased M30 fragments of CK18 levels may be useful as a possible marker of early tumor invasiveness.

Cited by 8 publications

References 35 publications

Precancer antiviral treatment reduces microvascular invasion of early-stage Hepatitis B-related hepatocellular carcinoma

Precancer antiviral treatment reduces microvascular invasion of early-stage Hepatitis B-related hepatocellular carcinoma

Serum Cytokeratin 18 M30 Levels in Chronic Hepatitis B Reflect Both Phase and Histological Activities of Disease

Prognostic value of non-invasive serum Cytokeratin 18 detection in gastrointestinal cancer: a meta-analysis

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