ABSTRACT
BACKGROUND: The majority of hepatocellular carcinoma patients (HCCs) with extrahepatic metastases die of progressive intrahepatic tumor. There have been little data on the role of primary tumor resection (PTR) for HCCs with extrahepatic metastases but with resectable primary tumors. METHODS: A retrospective study was conducted on HCCs with extrahepatic metastases with resectable primary tumors who either underwent or did not undergo PTR in the SEER registry between 2004 and 2013. The overall and cancer-specific survivals (OS and CSS) were assessed by the log-rank test and the Cox proportional hazard regression model. A propensity score matching was conducted to minimize biases. Validation was performed in another cohort from the Sun Yat-sen Memorial Hospital (SYSMH). RESULTS: Of the 529 HCCs with extrahepatic metastases with resectable primary tumors included into this study, 230 patients underwent PTR and 299 did not. The percentages of patients who underwent PTR increased from 38.6% in 2004 to 70.3% in 2013. In the propensity score-matched patients, PTR was associated with improved OS (HR 0.310, P < 0.001) and CSS (HR 0.326, P <0.001). These improvements in survivals remained significant after sensitivity analyses using multiple imputation. In the validation cohort from the SYSMH (n = 131), PTR was also correlated with improved OS (HR 0.508, P = 0.002) and CSS (HR 0.568, P = 0.017). CONCLUSIONS: This study using propensity score matching and multiple imputation demonstrated that PTR had a favorable impact on the prognosis of HCCs with extrahepatic metastases with resectable primary tumors. Further prospective randomized trials are needed to confirm these findings.
Subject(s)
Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/pathology , Female , Hepatectomy , Humans , Kaplan-Meier Estimate , Liver Neoplasms/epidemiology , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , North America/epidemiology , Propensity Score , Proportional Hazards Models , Public Health Surveillance , Registries , Retrospective Studies , SEER Program , Young AdultABSTRACT
Deregulation of epigenetic modification by microRNAs (miRNAs) contributes to the development of estrogen deficiency, a hallmark of the multigenic endocrine disorder polycystic ovary syndrome (PCOS), but its etiology remains unclear. Previous study has pointed to a tight association between miR-320a expression and oocyte development in human follicular fluid. Given that the bi-directional communication existing between cumulus cells (CCs) and follicular fluid is essential for ovarian steroidogenesis and CCs are the main site where estrogen is finally synthesized, it is intriguing to know whether miR-320a have any regulatory roles in this unique cell. Here we report that miR-320a expression is significantly down-regulated in primary CCs from PCOS patients and this down-regulation promotes estrogen deficiency in CCs. From a mechanistic standpoint, IGF1 regulates miR-320a expression in CCs, and miR-320a could potentiate the steroidogenesis in CCs through modulation of CYP11A1 and CYP19A1 expression, by directly targeting 3'untranslated region (3'UTR) of the osteogenic transcription factor RUNX2. Overall, our results strongly suggest that deregulation of miR-320a/RUNX2/CYP11A1 (CYP19A1) cascade plays an important role in the development of estrogen deficiency in human CCs. Testing patients for miR-320a/RUNX2 expression ratios may provide more accurate diagnostic information and could influence the recommended course of treatment for PCOS.
