Impact of circulating tumor DNA in hepatocellular and pancreatic carcinomas

Dhayat, Sameer; Yang, Zixuan

doi:10.1007/s00432-020-03219-5

Cited by 16 publications

(17 citation statements)

References 159 publications

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“…Finally, our analysis supported the relationship between unresectable HCC with high intensity in the hepatobiliary phase of EOB-MRI and CTNNB-1 mutations determined by cfDNA analysis. The analysis of cfDNA is an effective method for the detection of genetic alterations in HCC [ 16 , 29 , 30 ], and it is less impacted by intratumoral heterogeneity than are analyses of single tumor tissue samples [ 31 ]. In three patients with unresectable HCC with high intensity in the hepatobiliary phase of EOB-MRI, CTNNB1 alterations in cfDNA were observed in two patients (66.7%, 2/3), while all four patients without HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI lacked mutations.…”

Section: Discussionmentioning

confidence: 99%

Characteristics and Lenvatinib Treatment Response of Unresectable Hepatocellular Carcinoma with Iso-High Intensity in the Hepatobiliary Phase of EOB-MRI

Kubo

Suda

Kimura

et al. 2021

Cancers

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In hepatocellular carcinoma (HCC), CTNNB-1 mutations, which cause resistance to immune checkpoint inhibitors, are associated with HCC with iso-high intensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) in resectable HCC; however, analyses on unresectable HCC are lacking. This study analyzed the prevalence, characteristics, response to lenvatinib, and CTNNB-1 mutation frequency in unresectable HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI. In 52 patients with unresectable HCC treated with lenvatinib, the prevalence of iso-high intensity in the hepatobiliary phase of EOB-MRI was 13%. All patients had multiple HCCs, and 3 patients had multiple HCCs with iso-high intensity in the hepatobiliary phase of EOB-MRI. Lenvatinib response to progression-free survival and overall survival were similar between patients with or without iso-high intensity in the hepatobiliary phase of EOB-MRI. Seven patients (three and four patients who had unresectable HCC with or without iso-high intensity in the hepatobiliary phase of EOB-MRI, respectively) underwent genetic analyses. Among these, two (67%, 2/3) who had HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI carried a CTNNB-1 mutation, while all four patients who had HCC without iso-high intensity in the hepatobiliary phase of EOB-MRI did not carry the CTNNB-1 mutation. This study’s findings have clinical implications for the detection and treatment of HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI.

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Section: Discussionmentioning

confidence: 99%

Characteristics and Lenvatinib Treatment Response of Unresectable Hepatocellular Carcinoma with Iso-High Intensity in the Hepatobiliary Phase of EOB-MRI

Kubo

Suda

Kimura

et al. 2021

Cancers

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“…Hepatocellular carcinoma (HCC) is the most common primary neoplasm of the liver. 120 Chen et al 121 found that METTL3 can promote the progression of liver cancer cells through YTHDF2-dependent transcriptional regulation of SOCS2 silencing. Further study showed that METTL14 interacted with DGCR8 and positively regulated the expression of miRNA 126.…”

Section: Review Llmentioning

confidence: 99%

RNA m6A Modification in Cancers: Molecular Mechanisms and Potential Clinical Applications

Shi

Dai

et al. 2020

The Innovation

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N 6 -Methyladenosine (m 6 A) RNA modification brings a new dawn for RNA modification researches in recent years. This posttranscriptional RNA modification is dynamic and reversible, and is regulated by methylases (“writers”), demethylases (“erasers”), and proteins that preferentially recognize m 6 A modifications (“readers”). The change of RNA m 6 A modification regulates RNA metabolism in eucaryon, including translation, splicing, exporting, decay, and processing. Thereby the dysregulation of m 6 A may lead to tumorigenesis and progression. Given the tumorigenic role of abnormal m 6 A expression, m 6 A regulators may function as potential clinical therapeutic targets for cancers. In this review, we emphasize on the underlying mechanisms of m 6 A modifications in tumorigenesis and further introduce the potential m 6 A regulators-associated therapeutic targets for tumor therapy.

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“…ctDNA can reflect tumor cytogenetics and epigenetic information ( 7 ). In the whole-cycle management of HCC, ctDNA monitoring can dynamically provide the information of tumor genetic variation, which has become a hot research direction in recent years ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of Tumor-Derived DNA on CXCL12-CXCR4 and CCL21-CCR7 Axes of Hepatocellular Carcinoma Cells and the Regulation of Sinomenine Hydrochloride

Shen

Li²,

Li³

et al. 2022

Front. Oncol.

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Currently, chemokines and their receptors, CXCL12-CXCR4 and CCL21-CCR7 axes, are deemed vital factors in the modulation of angiogenesis and are crucial for the growth and development of liver cancer. Tumor-derived DNA can be recognized by immune cells to induce an autoimmune response. In this study, we demonstrated the mechanism of tumor-derived DNA on the CXCL12-CXCR4 and CCL21-CCR7 axes of hepatocellular carcinoma (HCC) cells and the regulatory effect of sinomenine hydrochloride. Tumor-derived DNA was separated from HCCLM cell lines. Tumor-derived DNA was transfected into SK-Hep1 cells by Lipofectamine 2000. We found that sinomenine hydrochloride reduced the expression of CXCR4, CXCR12, CCR7, and CCL21 in HCC cells, suppressed the growth and invasion of HCC cells, and increased apoptosis. In contrast to the controls, the protein expressions of CXCR4, CXCL12, CCR7, CCL21, P-ERK1/2, MMP-9, and MMP-2 in SK-Hep1 cells were significantly increased after transfection of tumor-derived DNA, while the increase was reversed by sinobine hydrochloride. Acid sinomenine interferes with tumor-derived DNA and affects ERK/MMP signaling via the CXCL12/CXCR4 axis in HCC cells. CXCR4 siRNA and CCR7 siRNA attenuated tumor-derived DNA activation of ERK1/2/MMP2/9 signaling pathways in HCC cells. CXCR4-oe and CCR7-OE enhance the stimulation of erK1/2/MMP2/9 signaling pathway by tumor-derived DNA in HCC cells. Tumor-derived DNA reduced apoptosis and increased invasion of SK-Hep1 cells by CXCL12-CXCR4 axis and CCL21-CCR7 axis, and sinobine hydrochloride reversed this regulation. These results strongly suggest that tumor-derived DNA can increase the growth and invasion of oncocytes via the upregulation of the expression of CXCL12-CXCR4 and CCL21-CCR7 axis and through ERK1/2/MMP2/9 signaling pathway in HCC cells, and sinobine hydrochloride can inhibit this signaling pathway, thus inhibiting HCC cells. These results provide new potential therapeutic targets for blocking the progression of HCC induced by CXCL12-CXCR4 axis and CCL21-CCR7.

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Impact of circulating tumor DNA in hepatocellular and pancreatic carcinomas

Cited by 16 publications

References 159 publications

Characteristics and Lenvatinib Treatment Response of Unresectable Hepatocellular Carcinoma with Iso-High Intensity in the Hepatobiliary Phase of EOB-MRI

Characteristics and Lenvatinib Treatment Response of Unresectable Hepatocellular Carcinoma with Iso-High Intensity in the Hepatobiliary Phase of EOB-MRI

RNA m6A Modification in Cancers: Molecular Mechanisms and Potential Clinical Applications

Effects of Tumor-Derived DNA on CXCL12-CXCR4 and CCL21-CCR7 Axes of Hepatocellular Carcinoma Cells and the Regulation of Sinomenine Hydrochloride

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