Global DNA 5hmC and CK19 with 5hmC positives cell contents represent a promising biomarker for predicting prognosis in small hepatocellular carcinoma

Abstract Background: 5-Hydroxymethylcytosine (5hmC) exists dynamically and exhibits various regulatory functions. It’s possibly associated with tumor occurrence and malignant transformation. Nevertheless, the part of 5hmC in small hepatocellular carcinoma (SHCC) is still elusive. The study was directed toward characterizing 5hmC content in SHCC and assessing if global genomic 5hmC content was able to serve as a promising factor for predicting clinical results.Methods: The expression contens of 5mC, 5hmC and 5fC were assesed using ultra-high performance liquid chromatography tandem mass-spectrometry(UHPLC-MS/MS). 5hmC contens and CK19 expression were measured by immunohistochemistry(IHC) .Results: The findings in the study displayed that global genomic 5mC, 5hmC, and 5fC contents in SHCC specimens were globally reduced relative to para-tumor tissues (P<0.001), Lymph node metastasis may be found in the small HCC, the non-metastasis group exhibited higher 5mC and 5hmc contents relative to those in metastasis group (P<0.001). HBV DNA was relevant to the decrease in 5mC, 5hmC and 5fC, as evidenced by the measurements in cell lines carrying or not carrying HBV DNA. Moreover, the correlation analysis showed the negative correlation of the content of 5hmC with CK19 expression in SHCC. The decreases of both 5hmC and CK19 with 5hmC positives cell contents in genomic DNA were related to SHCC patients’ unfavorable prognosis. Compared with para-tumor tissues, the 5hmC content in SHCC specimems was dramatically reduced.Conclusions: 5hmC and CK19 with 5hmC positives cell contents in genomic DNA possibly serve as a promising biomarker for predicting prognosis in small hepatocellular carcinoma.

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Global DNA 5hmC and CK195hmC+ Contents: A Promising Biomarker for Predicting Prognosis in Small Hepatocellular Carcinoma

Current Oncology ◽

10.3390/curroncol28050321 ◽

2021 ◽

Vol 28 (5) ◽

pp. 3758-3770

Author(s):

Jinhua Jiang ◽

Tinghua Yan ◽

Fang Guo

Keyword(s):

Hepatocellular Carcinoma ◽

Genomic Dna ◽

High Performance ◽

Hbv Dna ◽

Tandem Mass ◽

Small Hepatocellular Carcinoma ◽

Node Metastasis ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass ◽

Regulatory Functions

Background: 5-Hydroxymethylcytosine (5hmC) with dynamic existence possesses multiple regulatory functions. Whereas, 5hmC’s impact on small hepatocellular carcinoma (SHCC) remains unclear. The present work focused on characterizing 5hmC content within SHCC and assessing the possibility of using global genomic 5hmC level as the predicative factor of clinical outcome. Methods: This study applied ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in measuring 5mC, 5fC and 5hmC contents. In addition, immunohistochemistry (IHC) was adopted to measure CK19 and 5hmC contents. Results: Research showed 5mC, 5hmC, and 5fC contents from global genomics of SHCC reduced extensively compared with healthy samples (p < 0.001). Moreover, SHCC was associated with lymph node metastasis (LNM). Greater 5mC and 5hmC levels were observed in non-metastasis group compared with the metastasis group (p < 0.001). Correlation analysis between the HBV DNA level and 5mC, 5fC and 5hmC levels exhibited that HBV DNA was associated with 5mC, 5hmC, and 5fC content reduction, which was verified in the cytological experiments. Moreover, 5hmC content had a negative correlation with the expression level of CK19 in SHCC. The decrease in 5hmC and CK19 containing 5hmC positive cell (called CK195hmC+) should be ascribed to the bad prognosis among SHCC patients. Conclusions: The contents of 5hmC and CK195hmC+ of genomic DNA might be adopted for predicting SHCC survival as an important biomarker.

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Quantification of 5-Methylcytosine and 5-Hydroxymethylcytosine in Genomic DNA from Hepatocellular Carcinoma Tissues by Capillary Hydrophilic-Interaction Liquid Chromatography/Quadrupole TOF Mass Spectrometry

Clinical Chemistry ◽

10.1373/clinchem.2012.193938 ◽

2013 ◽

Vol 59 (5) ◽

pp. 824-832 ◽

Cited By ~ 93

Author(s):

Ming-Luan Chen ◽

Fan Shen ◽

Wei Huang ◽

Jia-Hui Qi ◽

Yinsheng Wang ◽

...

Keyword(s):

Mass Spectrometry ◽

Hepatocellular Carcinoma ◽

Liquid Chromatography ◽

Genomic Dna ◽

Epigenetic Modification ◽

Hydrophilic Interaction Liquid Chromatography ◽

Hydrophilic Interaction ◽

Limits Of Detection ◽

Tumor Tissues ◽

Potential Biomarker

BACKGROUND 5-Methylcytosine (5-mC) is an important epigenetic modification involved in development and is frequently altered in cancer. 5-mC can be enzymatically converted to 5-hydroxymethylcytosine (5-hmC). 5-hmC modifications are known to be prevalent in DNA of embryonic stem cells and neurons, but the distribution of 5-hmC in human liver tumor and matched control tissues has not been rigorously explored. METHODS We developed an online trapping/capillary hydrophilic-interaction liquid chromatography (cHILIC)/in-source fragmentation/tandem mass spectrometry system for quantifying 5-mC and 5-hmC in genomic DNA from hepatocellular carcinoma (HCC) tumor tissues and relevant tumor adjacent tissues. A polymer-based hydrophilic monolithic column was prepared and used for the separation of 12 nucleosides by cHILIC coupled with an online trapping system. Limits of detection and quantification, recovery, and imprecision of the method were determined. RESULTS Limits of detection for 5-mC and 5-hmC were 0.06 and 0.19 fmol, respectively. The imprecision and recovery of the method were determined, with the relative SDs and relative errors being <14.9% and 15.8%, respectively. HCC tumor tissues had a 4- to 5-fold lower 5-hmC content compared to tumor-adjacent tissues. In addition, 5-hmC content highly correlated with tumor stage (tumor-nodes-metastasis, P = 0.0002; Barcelona Clinic liver cancer, P = 0.0003). CONCLUSIONS The marked depletion of 5-hmC may have profound effects on epigenetic regulation in HCC and could be a potential biomarker for the early detection and prognosis of HCC.

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Development, validation, and clinical application of a high-performance liquid chromatography-tandem mass spectrometry assay for the quantification of total intracellular β-decitabine nucleotides and genomic DNA incorporated β-decitabine and 5-methyl-2′-deoxycytidine

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2018.10.001 ◽

2019 ◽

Vol 164 ◽

pp. 16-26 ◽

Cited By ~ 3

Author(s):

Jeroen Roosendaal ◽

Hilde Rosing ◽

Luc Lucas ◽

Aram Oganesian ◽

Jan H.M. Schellens ◽

...

Keyword(s):

Mass Spectrometry ◽

High Performance Liquid Chromatography ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Genomic Dna ◽

High Performance ◽

Tandem Mass ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass ◽

Mass Spectrometry Assay

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Comparison of open liver resection and RFA for the treatment of solitary 3-5 cm hepatocellular carcinoma: a retrospective study

10.21203/rs.2.11159/v5 ◽

2019 ◽

Author(s):

Jianyong Lei ◽

LN Yan ◽

DJ Li ◽

WT Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Resection ◽

Cox Regression ◽

Survival Rates ◽

Significant Risk ◽

Significant Risk Factor ◽

Clinical Results ◽

Small Hepatocellular Carcinoma ◽

Free Survival ◽

Cox Regression Analysis

Abstract Background: The goal of this study was to compare the postoperative results of liver resection and radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (HCC) (3-5 cm). Patients and methods: We retrospectively collected 122 cases of small solitary HCC treated at our center from Jan 2011 to Dec 2015, with diameters in the range of 3-5 cm. According to the treatment program received at our center, the patients were divided into liver resection (72 patients) and RFA (50 patients) groups. Result: In comparison with the RFA group, the resection group had a longer operative time, greater intraoperative blood loss (P<0.01), more hepatic inflow occlusion, and a longer postoperative hospital stay (P<0.01). The 1-, 3-, and 5-year expected overall survival rates and tumor-free survival rates were comparable between the two groups. Cox regression analysis showed that neither resection nor RFA was a significant risk factor for overall or tumor-free survival in HCC. Conclusions: For solitary HCC of 3-5 cm in diameter, RFA can achieve better in-hospital clinical results and similar long-term outcomes than resection and can be considered for wide application, especially for central-location cases.

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Serum and tissue PIVKA-II expression reflect the biological malignant potential of small hepatocellular carcinoma

Gastroenterology ◽

10.1016/s0016-5085(01)82773-6 ◽

2001 ◽

Vol 120 (5) ◽

pp. A558-A558

Author(s):

M TAMANO ◽

K KOJIMA ◽

M OGUMA ◽

M LIJIMA ◽

T MUROHISA ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Malignant Potential ◽

Small Hepatocellular Carcinoma

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Early and non-invasive diagnosis of small hepatocellular carcinoma using real-time elastography

Ultraschall in der Medizin - European Journal of Ultrasound ◽

10.1055/s-2008-1079787 ◽

2008 ◽

Vol 29 (S 1) ◽

Author(s):

L Gheorghe ◽

S Iacob ◽

I Lupescu ◽

G Becheanu ◽

M Dumbrava ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Real Time ◽

Small Hepatocellular Carcinoma ◽

Non Invasive

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199. Identification of a Major Human Metabolite of Acetochlor in Exposed Herbicide Applicators by High Performance Liquid Chromatography-Tandem Mass Spectrometry

10.3320/1.2758910 ◽

2006 ◽

Author(s):

C. Hines ◽

C. Striley ◽

D. Barr ◽

A. Olsson ◽

R. Bravo ◽

...

Keyword(s):

Mass Spectrometry ◽

High Performance Liquid Chromatography ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

High Performance ◽

Tandem Mass ◽

Human Metabolite ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass

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Transcatheter Chemoembolization of a Hepatocellular Carcinoma Utilizing Lipiodol through the Pancreaticoduodenal Arcade: A Case Report

American Journal of Interventional Radiology ◽

10.25259/ajir-19-2018 ◽

2018 ◽

Vol 2 ◽

pp. 5

Author(s):

Scott P Patterson ◽

Richard G Foster

Keyword(s):

Hepatocellular Carcinoma ◽

Case Report ◽

Vascular Anatomy ◽

Left Gastric Artery ◽

Target Lesion ◽

Celiac Artery ◽

Small Hepatocellular Carcinoma ◽

Gastric Artery ◽

Variant Anatomy ◽

Pancreaticoduodenal Arcade

This case report describes the chemoembolization of a small hepatocellular carcinoma employing a lipiodol drug delivery system utilizing a novel arterial pathway. Because the target lesion was precariously located adjacent to the inferior heart border and the diaphragm, it was unsuitable for imaging-guided microwave ablation. To achieve chemoembolization, several intraprocedural adaptations were necessary, given the variant anatomy encountered and difficulty accessing the left gastric artery through a celiac artery approach. The left gastric artery was selected from a superior mesenteric artery approach through the pancreaticoduodenal arcade (Rio Branco’s arcade). This case illustrates the importance of a mastery of the vascular anatomy and variants of hepatic arterial flow.

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