Circulating cell-free DNA as a predictive marker for distant metastasis of hepatitis C virus-related hepatocellular carcinoma

Tokuhisa, Yoshihiro; Iizuka, Norio; Sakaida, Isao; Moribe, Toyoki; Fujita, Nozomi; Miura, Toshiaki; Tamatsukuri, Shigeru; Ishitsuka, Hideo; Uchida, Kenichiro; Terai, Shuji; Sakamoto, Kazuhiko; Tamesa, Takao; Oka, M.

doi:10.1038/sj.bjc.6604034

Cited by 83 publications

(63 citation statements)

References 26 publications

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“…Although the physiological events leading to the increase of cfNAs during cancer development and progression are not well understood, specific cfNAs present in serum and other body fluids may represent potential biomarkers that could be used as a non-invasive, rapid, sensitive and accurate method of diagnosis and prognosis of cancer and/or metastasis [25–27]. In addition to their potential application as prognostic markers, cfNAs may also guide treatment decisions, as a rise or decline in circulating levels may predict therapy response earlier than conventional evaluation [22, 28]. Furthermore, cfNAs with a functional role in caner or metastatic progression could serve as new therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Regulation of cancer metastasis by cell-free miRNAs

Alečković

Kang

2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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MicroRNAs (miRNAs) are integral molecules in the regulation of numerous physiological cellular processes that have emerged as critical players in cancer initiation and metastatic progression, both by promoting and suppressing metastasis. Recently, cell-free miRNAs shed from cancer cells into circulation have been reported in cancer patients, raising hope for development of novel biomarkers that can be routinely measured in easily accessible samples. In fact, establishing miRNA expression in the circulation likely has advantages over determination in primary tumor tissue, further augmenting the potential applications of miRNA detection in oncological practice. In addition, secretion of miRNAs impacting distant cell signaling or promoting the formation of a niche that sustains a distant tumor microenvironment allows for new treatment approaches to thwart cancer progression.

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Section: Introductionmentioning

confidence: 99%

Regulation of cancer metastasis by cell-free miRNAs

Alečković

Kang

2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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“…However, mRNA analysis requires a tissue specimen to obtain high quality RNA which is an invasive procedure for the patient. It has been reported that increased levels of cell-free circulating DNA is present in many cancer patients including those with HCC (34,35), although cancer-specific DNA was less than 5% of the total circulating DNA (36,37). Aberrant methylation of p16, GSTP1 or RASSF1A has been frequently detected in the circulating DNA isolated from HCC patients (38)(39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

The assessment of methylated BASP1 and SRD5A2 levels in the detection of early hepatocellular carcinoma

Oka¹

2009

Int J Oncol

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Abstract. We previously identified BASP1 and SRD5A2 as novel hepatocellular carcinoma (HCC) methylation markers from among more than 10,000 screened genes. The present study aimed to improve the diagnostic potential of these genes. We compared the methylation status at distinct regions of the BASP1 and SRD5A2 genes using quantitative methylationspecific PCR, in 46 sets of HCC and corresponding non-tumor liver tissues. We also examined how their epigenetic status affected transcript levels in tissues and several hepatoma cell lines. We found that BASP1 and SRD5A2 loci were methylated in greater than 50% of the HCC tissues. Inverse correlations were identified between the methylation status and transcript levels in the tissues. Assessment of CpG island methylation rate of BASP1 and SRD5A2 resulted in different diagnostic powers for discriminating HCC even in the same CpG island. A combination analysis of BASP1 and SRD5A2 resulted in the optimum diagnostic performance (84.8% sensitivity and 91.3% specificity) with a maximal area under the receiver operating characteristic curve of 0.878. Even in patients with early HCC (well-differentiated, TNM stage I and small in diameter) and those negative for serum ·-fetoprotein, combination analysis enabled an accurate diagnosis of HCC. In vitro analysis also showed that BASP1 and SRD5A2 transcripts were epigenetically regulated by methylation and acetylation. These results suggest that combined analysis of methylated BASP1 and SRD5A2 may prove useful in the accurate diagnosis of HCC, especially early HCC. IntroductionHepatocellular carcinoma (HCC) may develop from chronic liver diseases caused by hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, and represents a major international health problem due to its increasing incidence in many countries (1,2). HCC is also one of the most common fatal cancers identified worldwide, as the vast majority of cases are first diagnosed at an advanced stage since a reliable diagnostic test for the detection of HCC, among at-risk individuals with chronic hepatitis and liver cirrhosis, is currently unavailable (1,2). To date, ·-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) have served as the predominant markers used in the screening for HCC (3). However, these tumor markers exhibit numerous limitations in the early detection of HCC. The identification of robust biomarkers for early diagnosis of HCC is urgently required.Several investigators have hypothesized that not only genetic mutation, but also epigenetic alterations, including aberrant methylation on CpG islands, is a fundamental contributor to carcinogenesis and tumor progression (3-5). Numerous studies have documented aberrant methylation of CpG islands in various cancers including HCC (6-11), supporting the hypothesis that detection of methylation on specific genes derived from cancer cells may be useful for accurate cancer diagnosis.Our recent genome-wide study identified DNA methylation at the Brain abundant, membrane attached sig...

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“…In contrast to RNA detection, serum levels of circulating cell-free DNA (cf-DA) were correlated to serum aminotransferase levels and to blood counts of neutrophils and leukocytes, which reflects an inflammatory process in HCV patients with HCC [33]. A separate study found that cf-DNA levels predicted distant metastases after curative treatment in HCV patients with HCC [34]. Thus, these nucleotide detection methods may have clinical values in reflecting progression, metastasis or prognosis; however they are less helpful in the detection of HCC CTCs.…”

Section: Detection Of Tumor-specific Mrna Mirna and Tumor Cell-free Dnamentioning

confidence: 99%

Capturing circulating tumor cells of hepatocellular carcinoma

Wu¹,

Pan²,

Pei³

et al. 2012

Cancer Letters

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a b s t r a c tEarly metastases of hepatocellular carcinoma (HCC) may be detected by the isolation of circulating tumor cells (CTCs) in the bloodstream. During the course of therapeutic attempts, monitoring CTC changes in patients with HCC is helpful for the efficacy assessment. Nevertheless, the markers used for the detection, such as a-feto protein, asialoglycoprotein receptor or epithelial cell adhesion molecule, CD133 or CD90, are not specific for HCC CTCs. In spite of these limitations, a timely determination of the existence of CTCs will be beneficial for the monitoring of distant metastases, the evaluation of therapeutic attempts, and the prediction of prognosis.

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Circulating cell-free DNA as a predictive marker for distant metastasis of hepatitis C virus-related hepatocellular carcinoma

Cited by 83 publications

References 26 publications

Regulation of cancer metastasis by cell-free miRNAs

Regulation of cancer metastasis by cell-free miRNAs

The assessment of methylated BASP1 and SRD5A2 levels in the detection of early hepatocellular carcinoma

Capturing circulating tumor cells of hepatocellular carcinoma

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