circRPS16 Promotes Proliferation and Invasion of Hepatocellular Carcinoma by Sponging miR-876-5p to Upregulate SPINK1.

The roles of serine protease inhibitor Kazal type 1 (SPINK1) in multiple types of cancers have been significantly documented. However, its specific roles in hepatocellular carcinoma (HCC) remain to be investigated. This study found that SPINK1 is upregulated in HCC and its upregulation correlates with poor prognosis. Besides, functional assays revealed that SPINK1 promotes cell proliferation, cell cycle, and invasion in vitro. Through bioinformatics analysis, we speculate that circRPS16 regulates SPINK1 expression by sponging miR-876-5p. This was further verified by the dual-luciferase reporter and fluorescent in situ hybridization (FISH) assays. Subsequently, rescue assays verified that circRPS16 promotes cell proliferation, cell cycle, and invasion through miR-876-5p. Importantly, silencing circRPS16 inhibited tumor growth by downregulating SPINK1 expression in vivo. Collectively, our results confirm that SPINK1 is a downstream target of circRPS16. Besides, circRPS16 and SPINK1 are oncogenic factors in HCC progression; they provide novel diagnostic and therapeutic targets for HCC patients.

Meta-analysis of the prognostic value of pretreatment serum ferritin in hepatobiliary and pancreas (HBP) cancers.

BACKGROUND AND OBJECTIVES: Studies have shown that serum ferritin (SF) has unfavourable prognostic value in hepatobiliary and pancreas (HBP) cancers. This meta-analysis aimed to comprehensively assess the prognostic role of pretreatment SF in patients with HBP cancers. METHODS: Eligible studies published before January 2020 were obtained through a comprehensive search in the PubMed, Web of Science, Cochrane Library and EMBASE databases. Pooled HRs and 95% CIs were then employed as effect sizes. RESULTS: Seven studies comprising 1244 patients were pooled. Elevated pretreatment SF was associated with worse overall survival (OS) (HR 1.60, 95% CI 1.36 to 1.88, p<0.001) and recurrence-free survival/progression-free survival/time to recurrence (HR 1.70, 95% CI 1.15 to 2.52, p=0.008). Significant prognostic value of elevated pretreatment SF on OS was detected in the subgroups regardless of the cancer type, race, SF cut-off value, tumour-node-metastasis stage and Newcastle-Ottawa Scale score. CONCLUSION: Elevated pretreatment SF was associated with worse survival outcome of patients with HBP cancers. As such, it may serve as a novel prognostic biomarker for HBP cancers.

Clinicopathological and prognostic value of preoperative lymphocyte to monocyte ratio for hepatocellular carcinoma following curative resection: A meta-analysis including 4,092 patients.

BACKGROUND: Previous studies have reported that lymphocyte-to-monocyte ratio (LMR) had novel prognostic value in hepatocellular carcinoma (HCC). The purpose of this meta-analysis was to synthetically evaluate the prognostic role of preoperative LMR in HCC patients following curative resection. METHODS: Eligible studies were acquired through searching Pubmed, Web of Science, Cochrane Library and EMbase update to September 2019. Merged hazard ratios (HRs) and 95% confidence intervals (CIs) were applied as effect sizes. RESULTS: A total of ten studies containing 4,092 patients following liver resection were enrolled in this meta-analysis. The pooled results demonstrated that preoperative elevated LMR indicated superior survival outcome (HR: 0.58, 95% CI: 0.34-0.96, P = .035) and recurrence-free survival (RFS)/disease-free survival/time to recurrence (HR = 0.76, 95% CI: 0.58-0.98, P = .034). The significant prognostic role of preoperative LMR was detected in the subgroup of all publication year, country of origin, sample sizes <300, TNM stage of I-IV and LMR cut-off value ≤4. Furthermore, high LMR was significantly associated with male, high AFP, large tumor size, incomplete tumor capsule, advanced TNM stage and BCLC stage, and presence of PVTT. CONCLUSION: Elevated preoperative LMR indicated superior survival outcome in HCC patients following curative resection, and might serve as a novel prognostic biomarker.

Circ_0091581 Promotes the Progression of Hepatocellular Carcinoma Through Targeting miR-591/FOSL2 Axis.

BACKGROUND: Circular RNAs (circRNAs) have shown crucial regulatory roles in cancer biology. We aimed to uncover the role and underlying mechanism of circ_0091581 in hepatocellular carcinoma (HCC) progression. METHODS: The abundance of circ_0091581, microRNA-591 (miR-591) and FOS like 2, AP-1 transcription factor subunit (FOSL2) was measured by quantitative real-time polymerase chain reaction. Cell viability, colony formation ability, and invasion ability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and transwell invasion assay. The migration ability was analyzed by transwell migration assay and wound healing assay. Flow cytometry was used to evaluate the cell cycle and apoptosis of HCC cells. The interaction between miR-591 and circ_0091581 or FOSL2 was predicted by Circular RNA Interactome database or TargetScan database and confirmed by dual-luciferase reporter assay and RNA immune co-precipitation assay. FOSL2 protein expression was measured by Western blot assay. Xenograft tumor assay was conducted to analyze the role of circ_0091581 in HCC tumor growth in vivo. RESULTS: Circ_0091581 was highly expressed in HCC tissue samples and cell lines in contrast to that in adjacent normal tissue samples and THLE-2 cell line. Circ_0091581 accelerated the viability, colony formation, metastasis, and cell cycle, while it impeded the apoptosis of HCC cells. MiR-591 bound to circ_0091581, and circ_0091581 knockdown-mediated effects in HCC cells were largely overturned by miR-591 silencing. FOSL2 was a target of miR-591, and FOSL2 overexpression largely reversed miR-591 accumulation-induced influences in HCC cells. FOSL2 protein expression was down-regulated by circ_0091581 silencing, and the addition of miR-591 inhibitor partly recovered the expression of FOSL2 in HCC cells. Circ_0091581 interference notably suppressed HCC tumor growth in vivo. CONCLUSION: Circ_0091581 acted as an oncogene to enhance the viability, colony formation, metastasis and cell cycle and inhibit the apoptosis of HCC cells through targeting miR-591/FOSL2 axis.

Prognostic value of lymphocyte to monocyte ratio in pancreatic cancer: a systematic review and meta-analysis including 3338 patients.

BACKGROUND: Recently, reports have classified lymphocyte to monocyte ratio (LMR) as an effective indicator for predicting the prognosis of pancreatic cancer. Nevertheless, the prognostic value of LMR for pancreatic cancer remains controversial. Through meta-analysis, this work intends to evaluate the potential prognostic role of pretreatment LMR in patients diagnosed with pancreatic cancer. METHODS: We reviewed and extracted eligible articles from Web of Science, PubMed, Cochrane Library, and Embase. A meta-analysis was conducted using hazard ratio (HR) and 95% confidence intervals (CIs) to assess the comparison between pretreatment LMR and overall survival (OS) and disease-free survival/recurrence-free survival/time to progression (DFS/RFS/TTP). RESULTS: In total, 11 studies (16 cohorts) including 3338 patients diagnosed with pancreatic cancer (PC) were enrolled in our meta-analysis. Notably, we revealed that high pretreatment LMR predicted better overall survival (OS) (HR = 0.68, 95% CI 0.58-0.80, P < 0.001, I-squared = 69.3%, Ph < 0.001) and DFS/RFS/TTP (HR = 0.55, 95% CI 0.31-0.96, P = 0.037, I-squared = 89.9%, Ph < 0.001) in patients with pancreatic cancer. Further, through subgroup analyses, we showed that high pretreatment LMR was significantly associated with the favorable OS regardless of ethnicity, study design, treatment method, variable type, the cut-off value for LMR, and disease stages of I-IV and III-IV. CONCLUSION: The findings from our study suggest that high pretreatment LMR is associated with better OS and DFS/RFS/TTP in patients diagnosed with pancreatic cancer. As such, it can potentially serve as a novel prognostic biomarker for patients with pancreatic cancer.

The Safety and Feasibility of Three-Dimensional Visualization Technology Assisted Right Posterior Lobe Allied with Part of V and VIII Sectionectomy for Right Hepatic Malignancy Therapy.

BACKGROUND: Hepatectomy is the optimal method for liver cancer; the virtual liver resection based on three-dimensional visualization technology (3-DVT) could provide better preoperative strategy for surgeon. We aim to introduce right posterior lobe allied with part of V and VIII sectionectomy assisted by 3-DVT as a promising treatment for massive or multiple right hepatic malignancies to retain maximum residual liver volume on the basis of R0 resection. METHODS: Among 126 consecutive patients who underwent hepatectomy, 9 (7%) underwent right posterior lobe allied with part of V and VIII sectionectomy. 21 (17%) underwent right hemihepatectomy (RH). The virtual RH was performed with 3-DVT, which provided better observation of spatial position relationship between tumor and vessels, and the more accurate estimation of the remnant liver volume. If remnant liver volume was <40%, right posterior lobe allied with part of V and VIII sectionectomy should be undergone. Then, the precut line ought to be planned on the basis of protecting the portal branch of subsegment 5 and 8. The postoperative outcome of patients was compared before and after propensity score matching. RESULTS: Nine patients meeting the eligibility criteria received right posterior lobe allied with part of V and VIII sectionectomy. The variables, including the overall mean operation time, blood transfusion, operation length, liver function, and postoperative complications, were similar between two groups before and after propensity matching. The postoperative first, third, fifth, and seventh days mean value of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), and total bilirubin had no significant difference compared with preoperative value. One patient in each group had recurrence six months after surgery. CONCLUSION: Right posterior lobe allied with part of V and VIII sectionectomy based on 3-DVT is safe and feasible surgery way, and can be a very promising method in massive or multiple right hepatic malignancy therapy.

Quantitative analysis of gadoxetic acid-enhanced magnetic resonance imaging predicts histological grade of hepatocellular carcinoma.

OBJECTIVE: To confirm the histological grade of hepatocellular carcinoma (HCC) by gadoxetic acid-enhanced MRI. METHODS: Ninety-five HCC patients underwent gadoxetic acid-enhanced MRI before surgical intervention. The correlations among the signal absolute enhancement, contrast enhancement ratio (CER) and tumor histological grade were analyzed. RESULTS: The correlation between CER of tumor-to-liver and the grades of tumor differentiation is the most significant negative. The k-value for the CER of tumor-to-liver and histopathologic analysis is 0.62, which gives evidence of good agreement. CONCLUSION: The quantitative analysis of gadoxetic acid-enhanced MRI can predict the histological grades of small HCCs.

Long-Term Outcomes of Hepatectomy for Bilateral Hepatolithiasis with Three-Dimensional Reconstruction: A Propensity Score Matching Analysis.

PURPOSE: Bilateral hepatolithiasis tends to show recurrent attacks, which may lead to liver damage and bile duct cancer. This study aimed to assess long-term outcome of hepatectomy for bilateral hepatolithiasis based on three-dimensional reconstruction. METHOD: A total of 258 bilateral hepatolithiasis patients were enrolled in this retrospective study from January 2008 to October 2014. There are 74 individuals in Three-Divisional Visualization System (MI-3DVS) group (group A) and 74 individuals in non-MI-3DVS group (group B) after propensity score matching (PSM), respectively. Then, complication incidence, stone clearance, recurrence, and recurrence-free survival rates were compared between the two groups. Multivariate Cox analysis was used to test impact of MI-3DVS on recurrence-free survival (RFS). RESULTS: The Median (Range) volumes of intraoperative blood loss were 300 (30-1050) and 400 (50-1800) mL in group A and B, respectively (P = .037). Meanwhile, immediate clearance (77% versus 53%, P = .002) and final clearance (95% versus 80%, P = .007) rates were higher in group A compared with values obtained for group B. Multivariate Cox analysis showed non-MI-3DVS (HR = 2.00, 95% confidence interval [CI] = 1.02-3.95, P = .045) and patients with bilateral cirrhosis (Hazard Ratio [HR] = 10.60, 95% CI = 4.45-25.25, P < .001) were independent predictors of RFS. CONCLUSION: Compared with conventional radiological technology, MI-3DVS-based hepatectomy resulted in higher stone clearance rate of bilateral hepatolithiasis patients. Non-MI-3DVS and patients with bilateral cirrhosis were independent predictors for recurrence-free survival.