Pulmonary Resection for Metastasis of Hepatocellular Carcinoma Recurring After Liver Transplant: An Italian Multicenter Experience

Invenizzi, Federica; Iavarone, M.; Donato, Maria Francesca; Mazzucco, A.; Torre, Massimo; Conforti, Serena; Rimessi, Arianna; Zavaglia, Claudio; Schiavon, Marco; Comacchio, Giovanni Maria; Rea, Federico; Boetto, Riccardo; Cillo, U.; Dondossola, Daniele; Carlis, Luciano De; Lampertico, Pietro; Nosotti, Mario; Mendogni, Paolo

doi:10.3389/fonc.2020.00381

Cited by 13 publications

(11 citation statements)

References 31 publications

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“…Amongst the subtypes of liver cancer, hepatocellular carcinoma (HCC) has the highest incidence and accounts for >80% of primary liver cancer types (3). Currently, there are various therapeutic approaches available for HCC, including surgical resection, cryotherapy, laser therapy and interventional surgery; however, due to the highly invasive and metastatic nature of HCC, the median survival time of patients with advanced HCC is only 3-6 months, and the 5-year survival rate remains at 12.5% (4,5). Therefore, the pathological mechanisms of HCC at the molecular level should be further investigated to determine effective treatment targets for HCC.…”

Section: Introductionmentioning

confidence: 99%

circ-PRKCI targets miR-1294 and miR-186-5p by downregulating FOXK1 expression to suppress glycolysis in hepatocellular carcinoma

Chen

Zhong

et al. 2021

Mol Med Rep

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Numerous human circular RNAs (circRNAs/circ) have been functionally characterized. However, the potential role of circ-protein kinase C iota (PRKCI) in hepatocellular carcinoma (HCC) remains unknown. The effects of each transfection and expression levels of circ-PRKCI, microRNA (miR)-1294, miR-186-5p and forkhead box K1 (FOXK1) in HCC cells were analyzed using reverse transcription-quantitative PCR analysis. The interactions between circ-PRKCI and miR-1294 or miR-186-5p, and miR-1294 or miR-186-5p and FOXK1 were validated using dual luciferase reporter assays. The viability, invasion and migration of HCC cells were determined using Cell Counting Kit-8, Transwell and wound healing assays, respectively. The expression levels of FOXK1, hexokinase-2 (HK2), glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA) in HCC cells were analyzed using western blotting. The levels of glucose and lactic acid in the cultured supernatant were detected using commercially available kits. The results of the present study revealed that miR-1294 and miR-186-5p expression levels were downregulated in the HCC cell line, HCCLM3, and were subsequently downregulated by circ-PRKCI overexpression and upregulated by the knockdown of circ-PRKCI. circ-PRKCI overexpression promoted the viability, invasion and migration of HCCLM3 cells, which was also reversed by the overexpression of miR-1294 and miR-186-5p. In addition, the overexpression of circ-PRKCI upregulated FOXK1 expression levels, while the overexpression of miR-1294 and miR-186-5p downregulated FOXK1 expression levels. Conversely, the knockdown of circ-PRKCI expression downregulated FOXK1 expression levels, while the knockdown of miR-1294 and miR-186-5p upregulated FOXK1 expression levels. Furthermore, circ-PRKCI was identified to target miR-1294 and miR-186-5p, and miR-1294 and miR-186-5p were subsequently found to target FOXK1. The overexpression of circ-PRKCI also increased glucose and lactic acid levels, while the knockdown of FOXK1 decreased glucose and lactic acid levels. The knockdown of circ-PRKCI decreased glucose and lactic acid levels, which were reversed by FOXK1 overexpression. In conclusion, the findings of the present study suggested that circ-PRKCI may promote the viability, invasion and migration of HCC cells by sponging miR-1294 and miR-186-5p to upregulate FOXK1 expression levels.

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Section: Introductionmentioning

confidence: 99%

circ-PRKCI targets miR-1294 and miR-186-5p by downregulating FOXK1 expression to suppress glycolysis in hepatocellular carcinoma

Chen

Zhong

et al. 2021

Mol Med Rep

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“…Lung is the most common site of recurrence, probably owing to proximity to the liver at the time of hepatectomy, and the lymphatic drainage [45] . In our study, we also observed that lungs were the most frequent site of HCC recurrence.…”

Section: Discussionmentioning

confidence: 99%

“…In a large series of pulmonary metastatectomy cases post LT, Hwang et al [48] showed that those patients who were selected for surgery based on the feasibility of complete resection and sufficient pulmonary function after surgery, the 5-year survival rate was significantly better. A large Italian multicenter study [45] found that pulmonary metastatectomy with a low complication rate was feasible in patients who were judged operable when they developed pulmonary metastasis as the first metastasis after LT for HCC. One year, 3-yr, and 5-yr cumulative overall survival rates of 100%, 66%, and 43%, respectively, were reported in this study, with a median OS of 51 months.…”

Section: Discussionmentioning

confidence: 99%

Post liver transplant recurrence in patients with hepatocellular carcinoma: not necessarily the end of the road!

Bhangui¹,

Yadav²,

Soin³

2020

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Aim: We analysed outcomes using multimodality therapy in patients with hepatocellular carcinoma (HCC) recurrence post living donor liver transplantation (LDLT). Methods: Of 2363 LDLT's performed between 2005 to mid 2018, 435 (18.4%) were for HCC within our expanded selection criteria (absence of extrahepatic disease and vascular invasion, irrespective of tumor size and number). Survival after recurrence, and prognostic factors for these patients were studied. Results: Of 435 LDLT patients, 51% had HCC beyond Milan and 43% beyond UCSF criteria at the time of LDLT. pre-LT AFP > 100 ng/mL and tumour FDG-18 PET avidity predicted overall survival (OS), whereas pre-LT AFP > 100 ng/mL, UCSF criteria, and FDG-18 PET avidity predicted recurrence-free survival. Hundred patients (23%) developed HCC recurrence at a median time of 16 months (range 2-108 months) post LDLT. Lungs (53%), liver (37%), and bone (21%) were the most common sites of recurrence. Ninety-five patients received tyrosine kinase inhibitors (TKI) after recurrence and 62 received mTOR inhibitors (protocol-based after LDLT, or post recurrence). Surgical resection of metastases was performed in 14 patients, 15 received stereotactic body radiotherapy, and 18 underwent ablation (radiofrequency, microwave ablation, transarterial chemoembolisation, or percutaneous ethanol injection). One-and 3-yr OS after recurrence were 57%, and 24% respectively, with a maximum post recurrence survival of 7.

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“…V jiné práci u pacientů pouze se systémovou léčbou sorafenib-lenvatinib byl medián přežití 19,5 měsíce [38]. Italská multicentrická studie uvádí u pacientů, kteří podstoupili resekci plicních metastáz, pravděpodobnost 5letého přežívání 43 % a medián přežívání 51 měsíců [39].…”

Section: Transplantace Jater Pro Rekurenci Hcc Po Resekci Nebo Ablaciunclassified

Hepatocellular carcinoma from the view of a transplant surgeon

Kočík¹,

Taimr²,

Froněk³

2020

Klin Onkol

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Pulmonary Resection for Metastasis of Hepatocellular Carcinoma Recurring After Liver Transplant: An Italian Multicenter Experience

Cited by 13 publications

References 31 publications

circ-PRKCI targets miR-1294 and miR-186-5p by downregulating FOXK1 expression to suppress glycolysis in hepatocellular carcinoma

circ-PRKCI targets miR-1294 and miR-186-5p by downregulating FOXK1 expression to suppress glycolysis in hepatocellular carcinoma

Post liver transplant recurrence in patients with hepatocellular carcinoma: not necessarily the end of the road!

Hepatocellular carcinoma from the view of a transplant surgeon

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