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TP53 mutation detected in circulating exosomal DNA is associated with prognosis of patients with hepatocellular carcinoma

Exosome DNA (exoDNA) can be used for liquid biopsy. This study was the first to use droplet digital PCR (ddPCR) to detect tumor-specific mutations in exoDNA and to evaluate the prognosis of hepatocellular carcinoma (HCC) patients. 60 HCC patients were enrolled in the study. We used ddPCR to detect c...

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Autores principales: Li, Yong, Wu, Junjun, Li, Enliang, Xiao, Zhouqing, Lei, Jun, Zhou, Fan, Yin, Xiangbao, Hu, Dandan, Mao, Yilei, Wu, Linquan, Wenjun, Liao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354767/
https://www.ncbi.nlm.nih.gov/pubmed/35921289
http://dx.doi.org/10.1080/15384047.2022.2094666
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author Li, Yong
Wu, Junjun
Li, Enliang
Xiao, Zhouqing
Lei, Jun
Zhou, Fan
Yin, Xiangbao
Hu, Dandan
Mao, Yilei
Wu, Linquan
Wenjun, Liao
author_facet Li, Yong
Wu, Junjun
Li, Enliang
Xiao, Zhouqing
Lei, Jun
Zhou, Fan
Yin, Xiangbao
Hu, Dandan
Mao, Yilei
Wu, Linquan
Wenjun, Liao
author_sort Li, Yong
collection PubMed
description Exosome DNA (exoDNA) can be used for liquid biopsy. This study was the first to use droplet digital PCR (ddPCR) to detect tumor-specific mutations in exoDNA and to evaluate the prognosis of hepatocellular carcinoma (HCC) patients. 60 HCC patients were enrolled in the study. We used ddPCR to detect c.747 G > T mutation in TP53 gene. We analyzed the correlation between detectable mutation in exoDNA and clinicopathologic characteristics using Multivariate logistics regression analysis. We performed Cox regression to assess the correlation between mutation frequency (mutant droplets/total droplets, MD/TD) and prognostic. We found that 48 of 60 patients had c.747 G > T mutation in TP53 gene in exoDNA (80.0%). We found that detectable mutation in exoDNA and age were associated with microvascular invasion (MVI) (P < .01). The ROC curve analysis revealed that the best cutoff value of mutation frequency to predict MVI was 67% (sensitivity 48.15%, specificity 93.94%,), the corresponding AUC was 0.761 (95%CI, 0.640–0.866; P < .01). Furthermore, we found that patients suffered high-frequency mutation (>67%) had shorted median recurrence-free survival (RFS) with 63 days (range, 53–202 days), compared with 368 days (range, 51–576 days) for patients with low-frequency mutation (<67%) (HR:4.61; 95% CI, 1.70–12.48; P = 0 .003). We also found that high-frequency mutation was associated with poor prognosis though patients had better pathological characteristics, such as AFP (<400 ng/mL), Liver cirrhosis (Negative), Tumor thrombus (Negative), Tumor numbers (Single) and Post-operation TACE (Executed). We provided evidence that the mutations in exoDNA might be used to predict patients with poor RFS. Abbreviations: TP53: Tumor protein p53; ExoDNA: Exosomal DNA; HCC: Hepatocellular carcinoma; ddPCR: Droplet digital Polymerase Chain Reaction (PCR); MD/TD: The ratio of mutant droplets/total droplets; AFP: Alpha-fetoprotein; MVI: Microvascular invasion; RFS: Recurrence-free survival.
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spelling pubmed-93547672022-08-06 TP53 mutation detected in circulating exosomal DNA is associated with prognosis of patients with hepatocellular carcinoma Li, Yong Wu, Junjun Li, Enliang Xiao, Zhouqing Lei, Jun Zhou, Fan Yin, Xiangbao Hu, Dandan Mao, Yilei Wu, Linquan Wenjun, Liao Cancer Biol Ther Research Paper Exosome DNA (exoDNA) can be used for liquid biopsy. This study was the first to use droplet digital PCR (ddPCR) to detect tumor-specific mutations in exoDNA and to evaluate the prognosis of hepatocellular carcinoma (HCC) patients. 60 HCC patients were enrolled in the study. We used ddPCR to detect c.747 G > T mutation in TP53 gene. We analyzed the correlation between detectable mutation in exoDNA and clinicopathologic characteristics using Multivariate logistics regression analysis. We performed Cox regression to assess the correlation between mutation frequency (mutant droplets/total droplets, MD/TD) and prognostic. We found that 48 of 60 patients had c.747 G > T mutation in TP53 gene in exoDNA (80.0%). We found that detectable mutation in exoDNA and age were associated with microvascular invasion (MVI) (P < .01). The ROC curve analysis revealed that the best cutoff value of mutation frequency to predict MVI was 67% (sensitivity 48.15%, specificity 93.94%,), the corresponding AUC was 0.761 (95%CI, 0.640–0.866; P < .01). Furthermore, we found that patients suffered high-frequency mutation (>67%) had shorted median recurrence-free survival (RFS) with 63 days (range, 53–202 days), compared with 368 days (range, 51–576 days) for patients with low-frequency mutation (<67%) (HR:4.61; 95% CI, 1.70–12.48; P = 0 .003). We also found that high-frequency mutation was associated with poor prognosis though patients had better pathological characteristics, such as AFP (<400 ng/mL), Liver cirrhosis (Negative), Tumor thrombus (Negative), Tumor numbers (Single) and Post-operation TACE (Executed). We provided evidence that the mutations in exoDNA might be used to predict patients with poor RFS. Abbreviations: TP53: Tumor protein p53; ExoDNA: Exosomal DNA; HCC: Hepatocellular carcinoma; ddPCR: Droplet digital Polymerase Chain Reaction (PCR); MD/TD: The ratio of mutant droplets/total droplets; AFP: Alpha-fetoprotein; MVI: Microvascular invasion; RFS: Recurrence-free survival. Taylor & Francis 2022-08-03 /pmc/articles/PMC9354767/ /pubmed/35921289 http://dx.doi.org/10.1080/15384047.2022.2094666 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Li, Yong
Wu, Junjun
Li, Enliang
Xiao, Zhouqing
Lei, Jun
Zhou, Fan
Yin, Xiangbao
Hu, Dandan
Mao, Yilei
Wu, Linquan
Wenjun, Liao
TP53 mutation detected in circulating exosomal DNA is associated with prognosis of patients with hepatocellular carcinoma
title TP53 mutation detected in circulating exosomal DNA is associated with prognosis of patients with hepatocellular carcinoma
title_full TP53 mutation detected in circulating exosomal DNA is associated with prognosis of patients with hepatocellular carcinoma
title_fullStr TP53 mutation detected in circulating exosomal DNA is associated with prognosis of patients with hepatocellular carcinoma
title_full_unstemmed TP53 mutation detected in circulating exosomal DNA is associated with prognosis of patients with hepatocellular carcinoma
title_short TP53 mutation detected in circulating exosomal DNA is associated with prognosis of patients with hepatocellular carcinoma
title_sort tp53 mutation detected in circulating exosomal dna is associated with prognosis of patients with hepatocellular carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354767/
https://www.ncbi.nlm.nih.gov/pubmed/35921289
http://dx.doi.org/10.1080/15384047.2022.2094666
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