Hepatitis B protein x (HBx) has been reported to promote tumorigenesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but the mechanism awaits further investigation. In this ...study, we found that cFAM210A (a circular RNA derived from the third exon of transcript NM_001098801 of the FAM210A gene; CircBase ID: hsa_circ_0003979) can be silenced by HBx. cFAM210A expression was downregulated and negatively correlated with tumorigenesis in patients with HBV-related HCC. Furthermore, cFAM210A reduced the proliferation, stemness, and tumorigenicity of HCC cells. Mechanistically, HBx increased the N6-methyladenosine (m6A) level of cFAM210A by promoting the expression of RBM15 (an m6A methyltransferase), thus inducing the degradation of cFAM210A via the YTHDF2-HRSP12-RNase P/MRP pathway. cFAM210A bound to YBX1 and inhibited its phosphorylation, suppressing its transactivation function toward MET. These findings suggest the important role of circular RNAs in HBx-induced hepatocarcinogenesis and identify cFAM210A a potential target in the prevention and treatment of HBV-related HCC.
The mechanism of hepatocellular carcinoma (HCC) metastasis remains poorly understood. Tropomodulin 3 (TMOD3) is a member of the pointed end capping protein family that contributes to invasion and ...metastasis in several types of malignancies. It has been found to be crucial for the membranous skeleton and embryonic development, although, its role in HCC progression remains largely unclear. We observed increased levels of Tmod3 in HCCs, especially in extrahepatic metastasis. High Tmod3 expression correlated with aggressive carcinoma and poor patient with HCC survival. Loss‐of‐function studies conducted by us determined Tmod3 as an oncogene that promoted HCC growth and metastasis. Mechanistically, Tmod3 increases transcription of matrix metalloproteinase‐2, ‐7, and ‐9 which required PI3K‐AKT. Interaction between Tmod3 and epidermal growth factor receptor (EGFR) that supports the activation of EGFR phosphorylation, is essential for signaling activation of PI3K‐AKT viral oncogene homolog. These findings reveal that Tmod3 enhances aggressive behavior of HCC both in vitro and in vivo by interacting with EFGR and by activating the PI3K‐AKT signaling pathway.
Abstract About 61–72% of transcribed regions possess long noncoding RNAs in antisense orientation (Antisense long noncoding RNAs, aslncRNAs). However, the function of aslncRNAs in HCC remains ...unclear. We found numerous aslncRNAs were deregulated and might be involved in regulatory gene-net of HCC. The PCNA-AS1, antisense to PCNA, is significantly up-regulated in HCC and could promote tumor growth in vitro and in vivo. The effects of PCNA-AS1 rely on regulation of PCNA via forming RNA hybridization to increase PCNA mRNA stability. We concluded that aslncRNAs might act as upstream regulators in HCC and PCNA-AS1 could serve as a novel therapeutic target.
Aberrant expression of MUC15 correlates with development of colorectal adenocarcinoma, and MUC15 has been reported to prevent trophoblast invasion of human placenta. However, little is known about ...the role of MUC15 in pathogenesis of hepatocellular carcinoma (HCC).
We analyzed HCC samples and matched nontumor liver tissues (controls) collected from 313 patients who underwent hepatectomy in Shanghai, China, from January 2006 through September 2009. Levels of messenger RNAs and proteins were determined by immunohistochemical, quantitative reverse transcription polymerase chain reaction, and immunoblot analyses. Statistical analyses were used to associate levels of MUC15 with tumor features and patient outcomes.
Levels of MUC15 messenger RNA and protein were reduced in a greater percentage of HCC samples than control tissues. Tumors with reduced levels of MUC15 were more likely to have aggressive characteristics (eg, high levels of α-fetoprotein, vascular invasion, lack of encapsulation, and poor differentiation) than those with low levels. Patients whose tumors had reduced levels of MUC15 had shorter overall survival times (24 months vs 46 months for patients with tumors with high levels of MUC15) and time to disease recurrence. Stable expression of MUC15 in HCC cell lines (SMMC-7721 and HCC-LM3) reduced their proliferation and invasive features in vitro, and ability to form metastatic tumors in mice. MUC15 reduced transcription of the matrix metalloproteinases 2 and 7 increased expression of tissue inhibitor of metalloproteinase-2, which required phosphoinositide 3-kinase−v-akt murine thymoma viral oncogene homolog signaling. Physical interaction between MUC15 and epidermal growth factor receptor led to its relocation and degradation within early endosomes and was required for inactivation of phosphoinositide 3-kinase−v-akt murine thymoma viral oncogene homolog signaling.
Reduced levels of MUC15 in HCCs are associated with shorter survival times of patients and reduced time to disease recurrence. Expression of MUC15 in HCC cells reduces their aggressive behavior in vitro and in mice by inducing dimerization of epidermal growth factor receptor and decreasing phosphoinositide 3-kinase signaling via v-akt murine thymoma viral oncogene homolog.
Single-Incision Laparoscopic Hepatectomy (SILH) through the umbilicus has been well-established for many years. However, pneumoperitoneum related complications that can occur with CO2 make many ...patients unable to tolerate pneumoperitoneum abandon laparoscopic surgery. This report describes a suspension transumbilical SILH.
Routine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic assessments and treatment decisions may ...benefit from the inclusion of tumor biological marker alpha-fetoprotein (AFP) and systemic inflammation indicator C-reactive protein (CRP).
Data from a multicenter cohort of 2770 HCC patients undergoing hepatectomy were analyzed. We developed the PACE risk score (Prognostic implications of AFP and CRP Elevation) after initially assessing preoperative AFP and CRP's prognostic value. Subgroup analyzes were performed in BCLC cohorts A and B using multivariable Cox analysis to evaluate the prognostic stratification ability of the PACE risk score and its complementary utility for BCLC staging.
Preoperative AFP ≥ 400ng/mL and CRP ≥ 10 mg/L emerged as independent predictors of poorer prognosis in HCC patients who underwent hepatectomy, leading to the creation of the PACE risk score. PACE risk score stratified patients into low, intermediate, and high-risk groups with cumulative 5-year overall (OS) and recurrence-free survival (RFS) rates of 59.6%/44.9%, 43.9%/38.4%, and 20.6%/18.0% respectively (all P < 0.001). Increased PACE risk scores correlated significantly with early recurrence and extrahepatic metastases frequency (all P < 0.001). The multivariable analysis identified intermediate and high-risk PACE scores as independently correlating with poor postoperative OS and RFS. Furthermore, the PACE risk score proficiently stratified the prognosis of BCLC stages A and B patients, with multivariable analyses demonstrating it as an independent prognostic determinant for both stages.
The PACE risk score serves as an effective tool for postoperative risk stratification, potentially supplementing the BCLC staging system.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
New Pt monolayer electrocatalysts were prepared using galvanic displacement of a copper monolayer deposited at underpotentials on a Pd core. By performing underpotential deposition twice, two ...monolayers were deposited, forming a core−shell structure with double shells. The double shells consist of an outermost shell of Pt monolayer and a sublayer shell of Pd−Au alloy. It was found that by adjusting the compositions of the alloy sublayer, it is possible to mediate the oxygen reduction reaction (ORR) activity of the Pt catalysts. An alloy with 10% (atomic) Au was found to be the most active among the catalysts tested. Furthermore, the catalysts showed good cycling stability that may be due to stabilizing effect of Au. Since different alloys can be used as the sublayer for mediation, this work may open up various opportunities to tailor electrocatalysts for best ORR activity.
There is a striking laterality in the site of hepatocellular carcinoma (HCC), with a strong predominance for the right side; however, the impact of primary tumor location on long-term prognosis after ...hepatectomy of HCC remains unclear. This study aimed to investigate the effect of primary tumor location on long-term oncological prognosis after hepatectomy for HCC.
Data of consecutive patients undergoing curative hepatectomy for HCC between 2008 and 2017 were analyzed. Overall survival (OS) and recurrence-free survival (RFS) of left-sided HCC (LS group) and right-sided HCC (RS group) were compared by using propensity score matching (PSM) analysis. COX regression analysis was performed to assess the adjusted effect of tumor location on long-term oncological prognosis.
Of the 2799 included patients, 707 (25.3%) and 2092 (74.7%) were in the LS and RS groups, respectively. Using PSM analysis, 650 matched pairs of patients were created. In the PSM cohort, median OS (66.0 vs. 72.0 months, P = 0.001) and RFS (28.0 vs. 51.0 months, P < 0.001) were worse among patients in the LS group compared to individuals in the RS group. After further adjustment for other confounders using multivariable COX regression analyses, HCC located on the left side remained independently associated with worse OS and RFS.
Tumors located on the left side are associated with poorer OS and RFS after hepatectomy for HCC. Careful surgical options selection and frequent follow-up to improve long-term survival may be justified for HCC patients with left-sided primary tumors.
Obesity is a major risk factor for hepatocellular carcinoma (HCC) and is typically accompanied by higher levels of serum dipeptidyl peptidase 4 (DPP4). However, the role of DPP4 in obesity-promoted ...HCC is unclear. Here, we found that consumption of a high-fat diet (HFD) promoted HCC cell proliferation and metastasis and led to poor survival in a carcinogen-induced model of HCC in rats. Notably, genetic ablation of DPP4 or treatment with a DPP4 inhibitor (vildagliptin) prevented HFD-induced HCC. Moreover, HFD-induced DPP4 activity facilitated angiogenesis and cancer cell metastasis in vitro and in vivo, and vildagliptin prevented tumor progression by mediating the pro-angiogenic role of chemokine ligand 2 (CCL2). Loss of DPP4 effectively reversed HFD-induced CCL2 production and angiogenesis, indicating that the DPP4/CCL2/angiogenesis cascade had key roles in HFD-associated HCC progression. Furthermore, concomitant changes in serum DPP4 and CCL2 were observed in 210 patients with HCC, and high serum DPP4 activity was associated with poor clinical prognosis. These results revealed a link between obesity-related high serum DPP4 activity and HCC progression. Inhibition of DPP4 may represent a novel therapeutic intervention for patients with HCC.
•Both genetic ablation and pharmacological inhibition of DPP4 prevented HFD-induced cancer vascularization and metastasis.•Tumor promotion effect of DPP4 was mediated by CCL2.•The concomitant changes of serum DPP4 and CCL2 were noted in liver cancer patients.•High serum DPP4 activity was closely associated with poor clinical prognosis.
The impact of antiviral therapy on long-term survival outcomes in patients with small HBV-related hepatocellular carcinoma (HBV-related HCC) after liver resection is still controversial, as the ...impact can be overshadowed by tumor-related factors. This study investigated this impact on recurrence and survival in patients with HCC of less than 3 cm.
This study was designed to further determine the impact of antiviral treatment on prognosis of patients with HCC after liver resection, to verify whether patients with cirrhosis still benefited from antiviral treatment, to study the impact of antiviral treatment on post-operative HCC recurrence, and to determine whether patients with a low preoperative HBV-DNA viral load should receive antiviral therapy.
The clinical data on patients who underwent curative liver resection for histopathologically confirmed small HCC (≤3 cm in diameter) were analyzed to determine factors which were related with HCC recurrence and survival. The disease-free and overall survival outcomes were estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify the risk factors of long-term survival.
Of the 795 patients in this study, patients with high preoperative HBV-DNA levels had significantly worse DFS and OS outcomes at 1-, 3- and 5- year after liver resection when compared with those with low HBV-DNA levels (86.1%, 60.8%, 46.6% vs 90.5%, 71.3%, 51.4%; and 98.5%, 89.3%, 75.2% vs 98.8%, 91.5%, 84%, respectively). Patients who received antiviral therapy had significantly better DFS and OS outcomes at 1-, 3- and 5- year after liver resection when compared with those without (91.6%, 69.5%, 55% vs 80.2%, 56%, 44.2%; and 99.6%, 93.5%, 87% vs 96.1%, 80.5%, 61.3%, respectively). Antiviral therapy significantly improved the OS but not DFS outcomes in patients with low HBV-DNA levels. The corresponding 1-, 3- and 5- year DFS and OS outcomes were 92.6%, 73%, 59.1% vs 87.1%, 68.5%, 57.9%; and 99.5%, 95.1%, 91.1% vs 97.6%, 85.5%, 72.4%, respectively. Antiviral treatment significantly prolonged DFS and OS in patients with cirrhosis. The corresponding 1-, 3- and 5- year DFS and OS were 90.2%, 66%, 49% vs 73.9%, 46.6%, 32.8%; and 100%, 93.6%, 85% vs 93.8%, 73.3%, 52.6%, respectively.
Antiviral therapy improved the prognosis of small HBV-related HCC of less than 3 cm. The survival benefit was also detected in patients with cirrhosis. Antiviral therapy should be considered a routine post-operative therapy for patients with HBV-related HCC.
As the tumor background, such as tumor size, can overshadow the impact of antiviral treatment, HCCs ≤3 cm were chosen to study the impact of antiviral therapy on postoperative long-term survival outcomes.the results shows:1)patients with low preoperative HBV-DNA who received antiviral therapy had better outcome than those who did not received.2)antiviral therapy improved disease free and overall survival in patients with cirrhosis after liver resection.3)antiviral therapy reduced hepatitis B terminal events in patients with small HBV-related hepatocellular carcinoma (HBV-related HCC) after liver resection.
