RESUMO
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in Egypt. A deep understanding of the molecular events occurring in HCC can facilitate the development of novel diagnostic and/or therapeutic approaches. In the present study, we describe a novel axis of hsa-circ-0000221-miR-661-PTPN11 mRNA proposed by in silico and in vitro analysis and its role in HCC pathogenesis. We observe a reduction in the expression levels of hsa-circ-0000221 and PTPN11 mRNA in HCC patients' sera tested compared with control subjects. The reduction occurs with a concomitant increase in the expression of miR-661. Furthermore, the introduction of exogenous hsa-circ-0000221 into Hep-G2 or SNU449 cell lines results in detectable decrease in cellular viability and an increase in apoptotic manifestations that is associated with G1 accumulation and CCDN1 overexpression. Altogether, these findings indicate the tumor-suppressive role of hsa-circ-0000221 in HCC, which acts through miR-661 inhibition, along with a subsequent PTPN11 mRNA increase, where PTPN11 is known to inhibit cell proliferation in many forms of cancer. Our study encourages further investigation of the role of circRNAs in cancer and their potential use as molecular biomarkers.
RESUMO
BACKGROUND AND AIM: The number of loco-regional therapies (LRTs) for hepatocellular carcinoma (HCC) has increased dramatically during the past decade, bridging or downstaging patients on the waiting list for liver transplantation. This study aimed to analyze the outcomes of LRTs prior to living donor liver transplantation in patients with HCC. METHODS: Sixty-two HCC patients received living donor liver transplantation at Ain Shams Center for Organ Transplantation over a 2-year period. Data from 29 HCC patients were analyzed. Twenty patients (68.97%) met the Milan Criteria and 4 patients (13.8%) exceeded the Milan Criteria, but met the University of California, San Francisco Criteria. Five patients (17.2%) exceeded the University of California, San Francisco Criteria. All patients underwent preoperative LRTs. The protocol of bridging/downstaging, methods, duration of follow-up, the number of patients who were successfully downstaged before liver transplantation (LT), and their outcomes after LT were recorded. RESULTS: There was a decrease in the mean overall size of focal lesions (from mean 5.46 to 4.11 cm) in the last abdominal computed tomography (CT) scan after LRT (p=0.0018). Discrepancies between the radiological findings and histopathology were as follows: in 16 patients (55.17%) the CT findings were consistent with the histopathological examination of the explanted liver. Underestimated tumor stage was documented in 10 patients (34.48%), and was overestimated by CT scan findings in 3 patients (10.34%). The 1-year survival rate was 93%. No patient had HCC recurrence after median follow-up of 21 months (range 1-46 months). CONCLUSION: These results encouraged tumor bridging/downstaging as a potential treatment option among carefully selected patients with HCC beyond conventional criteria for LT. Further studies on a large number of patients are necessary.
