A possible role of microRNAs as predictive markers for the recurrence of hepatocellular carcinoma after liver transplantation

Liese, Juliane; Peveling‐Oberhag, Jan; Doering, Claudia; Schnitzbauer, Andreas A.; Herrmann, Eva; Zangos, Stephan; Hansmann, Martin Leo; Moench, C.; Welker, Martin; Zeuzem, Stefan; Bechstein, Wolf O.; Ulrich, Frank

doi:10.1111/tri.12733

Cited by 29 publications

(25 citation statements)

References 55 publications

(77 reference statements)

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“…3 . A recurrence [GSE64989 ( 31 )] and two invasive datasets (GSE67139 and GSE67138) were also presented. Student's t-test revealed that miR-124-3p was significantly reduced in HCC compared to normal control samples with GSE 40744 data.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA‑124‑3p expression and its prospective functional pathways in hepatocellular carcinoma: A quantitative polymerase chain reaction, gene expression omnibus and bioinformatics study

Yang

Liang

et al. 2018

Oncol Lett

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The present study aimed to explore the potential clinical significance of microRNA (miR)-124-3p expression in the hepatocarcinogenesis and development of hepatocellular carcinoma (HCC), as well as the potential target genes of functional HCC pathways. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the expression of miR-124-3p in 101 HCC and adjacent non-cancerous tissue samples. Additionally, the association between miR-124-3p expression and clinical parameters was also analyzed. Differentially expressed genes identified following miR-124-3p transfection, the prospective target genes predicted in silico and the key genes of HCC obtained from Natural Language Processing (NLP) were integrated to obtain potential target genes of miR-124-3p in HCC. Relevant signaling pathways were assessed with protein-protein interaction (PPI) networks, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein Annotation Through Evolutionary Relationships (PANTHER) pathway enrichment analysis. miR-124-3p expression was significantly reduced in HCC tissues compared with expression in adjacent non-cancerous liver tissues. In HCC, miR-124-3p was demonstrated to be associated with clinical stage. The mean survival time of the low miR-124-3p expression group was reduced compared with that of the high expression group. A total of 132 genes overlapped from differentially expressed genes, miR-124-3p predicted target genes and NLP identified genes. PPI network construction revealed a total of 109 nodes and 386 edges, and 20 key genes were identified. The major enriched terms of three GO categories included regulation of cell proliferation, positive regulation of cellular biosynthetic processes, cell leading edge, cytosol and cell projection, protein kinase activity, transcription activator activity and enzyme binding. KEGG analysis revealed pancreatic cancer, prostate cancer and non-small cell lung cancer as the top three terms. Angiogenesis, the endothelial growth factor receptor signaling pathway and the fibroblast growth factor signaling pathway were identified as the most significant terms in the PANTHER pathway analysis. The present study confirmed that miR-124-3p acts as a tumor suppressor in HCC. miR-124-3p may target multiple genes, exerting its effect spatiotemporally, or in combination with a diverse range of processes in HCC. Functional characterization of miR-124-3p targets will offer novel insight into the molecular changes that occur in HCC progression.

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Section: Resultsmentioning

confidence: 99%

MicroRNA‑124‑3p expression and its prospective functional pathways in hepatocellular carcinoma: A quantitative polymerase chain reaction, gene expression omnibus and bioinformatics study

Yang

Liang

et al. 2018

Oncol Lett

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“…For example, decreased expression of miR-126 in HCC has been correlated with HCC recurrence and poor survival after liver transplantation [30]. In another study, a predictive score combining the expression levels of miR-214, miR-3187 and the Milan criteria was proposed to stratify patients according to their risk for recurrence of HCC and death after liver transplantation [31]. …”

Section: Discussionmentioning

confidence: 99%

High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12 months after resection

et al. 2017

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BackgroundHepatocellular carcinoma has a dismal prognosis due to recurrence rates of up to 70% after curative resection. Early recurrence is driven by synchronous microscopic intrahepatic metastases. The predictive value of histological parameters is discussed controversially and adjuvant therapy is not established. The aim of this study was to identify patients at high risk for early intrahepatic recurrence by expression profiling of selected micro RNAs.MethodsIn 52 patients undergoing HCC resection between 2011 and 2014, liver and tumor tissue was collected during surgery. Twelve patients with incomplete data regarding HCC recurrence, secondary liver transplantation, or perioperative death were excluded, leaving 40 patients with early recurrence <12 months (R+) or without recurrence for >24 months (R-) to compare grading, T, L, V, and R status. If tissue quality permitted, micro RNAs were measured in HCC and liver tissue.ResultsTen women and 30 men (64.0 ± 10.2 years) were analyzed. R+ occurred in 29 patients 6.2 ± 4.5 months after resection. Surveillance of R- was 26.2 ± 5.2 months. High intratumoral expression of miR-135a was associated with high risk of recurrence (HR = 4.2, p = 0.024, time to recurrence 8.8 ± 2.0 vs. 24.8 ± 4.4 months in patients with low miR-135a expression). As expected, T3 status was correlated with early recurrence, while other histological parameters and expression of miR-21, miR-122, and miR-125a did not.ConclusionsWe show a significant association between high expression of miR-135a and early HCC recurrence. Therefore, high intratumoral miR-135a expression might serve as a novel biomarker to identify patients urgently requiring adjuvant therapy post resection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3053-7) contains supplementary material, which is available to authorized users.

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“…Circulating miRNA has emerged as one of the most attractive tools for the early diagnosis of cancers [42][43][44]. Some authors have reported that miRNA markers were useful predictors of HCC recurrence after LT [42,[45][46][47]. In the near future, it is expected that the understanding of tumor biology will advance through further analysis of these molecular mechanisms, facilitating individual risk stratification for HCC patients who will benefit from LT [42].…”

Section: Discussionmentioning

confidence: 99%

Pharyngeal metastasis following living-donor liver transplantation for hepatocellular carcinoma: case report and review of literature

Tohyama¹,

Sakamoto²,

Tamura³

et al. 2020

Preprint

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Background: The most common sites of recurrence after liver transplantation for hepatocellular carcinoma (HCC) have been reported to be the liver, lung, bone, and adrenal glands, but there have also been many reports of cases of multiple recurrence. The prognosis after recurrence is poor, with reported median survival after recurrence of HCC ranging from 9 to 19 months. Here, we report a case of long-term survival after recurrence of pharyngeal metastasis following living-donor liver transplantation (LDLT) for HCC within the Milan criteria, by resection of the metastatic region and cervical lymph node dissection. Case presentation: A 47-year-old man with a Model End-stage Liver Disease (MELD) score of 11 underwent LDLT for HCC within the Milan criteria for liver cirrhosis associated with hepatitis B virus infection, with his 48-year-old elder brother as the living donor. One year and 10 months after liver transplantation, he visited a nearby hospital with a chief complaint of discomfort on swallowing. A pedunculated polyp was found in the hypopharynx, and biopsy revealed HCC metastasis. We performed pharyngeal polypectomy. Two years later, cervical lymph nodes metastasis appeared, and neck lymph node dissection was performed. Although recurrence subsequently occurred three times in the grafted liver, the patient is still alive 12 years and 10 months after recurrence of pharyngeal metastasis. He is now a tumor-free outpatient taking sorafenib. Conclusion: It is necessary to recognize that the nasopharyngeal region is a potential site of HCC metastasis. Prognostic improvement can be expected with close follow-up, early detection, and multidisciplinary treatment, including radical resection.

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A possible role of microRNAs as predictive markers for the recurrence of hepatocellular carcinoma after liver transplantation

Cited by 29 publications

References 55 publications

MicroRNA‑124‑3p expression and its prospective functional pathways in hepatocellular carcinoma: A quantitative polymerase chain reaction, gene expression omnibus and bioinformatics study

MicroRNA‑124‑3p expression and its prospective functional pathways in hepatocellular carcinoma: A quantitative polymerase chain reaction, gene expression omnibus and bioinformatics study

High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12 months after resection

Pharyngeal metastasis following living-donor liver transplantation for hepatocellular carcinoma: case report and review of literature

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