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Background Hepatocellular Carcinoma (HCC) is one of the major malignant tumors threatening human health. Lenvatinib resistance seriously restricts the efficacy of HCC, but the specific mechanism is not clear. Circular RNA (circRNA) plays an important role in the regulation of tumor drug resistance. Methods Key circRNA was screened by bioinformatics methods, and further identified by relevant validation experiments and HCC tissue samples. And, circRNA was evaluated as a diagnostic and prognostic marker for HCC progression at the clinical level. After then, through in vivo and in vitro experiments, the specific mechanism of the circRNA on the progression of HCC and lenvatinib resistance was explored at the molecular level. Results circRNA_0009792 (circRNA-mTOR) was highly expressed in HCC and is closely related to the prognosis of patients, which has good diagnostic value and clinical significance. In vivo and in vitro experiments showed that circRNA-mTOR could promote the progression of hepatocellular carcinoma and promote lenvatinib resistance by improving the stemness of HCC cells. Mechanismly, circRNA-mTOR could affect RNA-binding protein (PSIP1) nuclear translocation by specifically binding to it, and then which enhanced the stemness of HCC cells through PSIP1/c-Myc axis, hence promoting the progression of HCC and lenvatinib resistance. And furthermore, circRNA-mTOR at least partially induce lenvatinib resistance by increasing the expression of EGFR in HCC. Conclusions In conclusion, this study suggests that circRNA-mTOR can affect PSIP1/c-myc axis nuclear translocation, to make progress of HCC and the maintenance of steness of liver cancer cell to aggravate lenvatinib resistance, And partially increased EGFR over-expression to making chemo-resistance worse. CircRNA-mTOR has the potential to be a biomarker for the diagnosis and prognosis of HCC. This study provides a certain experimental basis for the targeted drug therapy of HCC, and puts forward new ideas, new insights and new methods in understanding the occurrence and development of HCC, and it is of great significance to seek new markers and targets for the diagnosis and treatment of HCC and reduce drug resistance.

The development of high-throughput technologies has yielded a large amount of data from molecular and epigenetic analysis that could be useful for identifying novel biomarkers of cancers. We analyzed Gene Expression Omnibus (GEO) DataSet micro-ribonucleic acid (miRNA) profiling datasets to identify miRNAs that could have value as diagnostic and prognostic biomarkers in hepatocellular carcinoma (HCC). We adopted several computing methods to identify the functional roles of these miRNAs. Ultimately, via integrated analysis of three GEO DataSets, three differential miRNAs were identified as valuable markers in HCC. Combining the results of receiver operating characteristic (ROC) analyses and Kaplan-Meier Plotter (KM) survival analyses, we identified hsa-let-7e as a novel potential biomarker for HCC diagnosis and prognosis. Then, we found via quantitative reverse-transcription polymerase chain reaction (RT-qPCR) that let-7e was upregulated in HCC tissues and that such upregulation was significantly associated with poor prognosis in HCC. The results of functional analysis indicated that upregulated let-7e promoted tumor cell growth and proliferation. Additionally, via mechanistic analysis, we found that let-7e could regulate mitochondrial apoptosis and autophagy to adjust and control cancer cell proliferation. Therefore, the integrated results of our bioinformatics analyses of both clinical and experimental data showed that let-7e was a novel biomarker for HCC diagnosis and prognosis and might be a new treatment target.

Long noncoding RNAs (lncRNAs), such as LINC00462, HOTAIR, and MALAT1, are significantly upregulated in hepatocellular carcinoma (HCC) tissues. However, lncRNA expression in the serum of HCC patients is still unclear. To identify candidate lncRNAs for HCC diagnosis, we purified exosomal total RNA from the serum of healthy volunteers (controls) and hepatitis, cirrhosis, and HCC patients. To assess the function of lncRNAs, small interfering RNAs and overexpression vectors were designed and cell viability and cell apoptosis assays conducted. The exosomes of the control group had a larger number of lncRNAs with a high amount of alternative splicing compared to hepatic disease patients. qPCR assays showed that lnc-FAM72D-3, lnc-GPR89B-15, lncZEB2-19, and lnc-EPC1-4 are differentially expressed in HCC. Furthermore, the expression level of lnc-EPC1-4 correlated with age. While the expression levels of lnc-GPR89B-15 and lnc-EPC1-4 correlated with serum alpha-fetoprotein level. lnc-FAM72D-3 knockdown decreased cell viability and promoted cell apoptosis, indicating that lnc-FAM72D-3 functions as an oncogene in HCC. In contrast, lnc-EPC1-4 overexpression inhibited cell proliferation and induced cell apoptosis, indicating that it functions as a tumor suppressor gene. Collectively, these findings show that lnc-FAM72D-3 and lnc-EPC1-4 play a novel role that might contribute to hepatocarcinogenesis and identify potential candidate biomarkers for HCC diagnosis.

BackgroundFor patients with hepatocellular carcinoma (HCC) with microvascular invasion (MVI) after curative resection, the effects of various postoperative adjuvant therapies are not summarized in detail, and the comparison between the effects of various adjuvant therapies is still unclear. Thus, we collected existing studies on postoperative adjuvant therapies for patients with HCC with MVI after curative resection and analyzed the effects of various adjuvant therapies.MethodWe collected all studies on postoperative adjuvant therapy for patients with HCC with MVI after curative resection from PubMed, EMBASE, Cochrane Library and SinoMed ending on May 1, 2019. Overall survival (OS) and disease-free/recurrence-free survival (RFS) between each group were compared in these studies by calculating the pooled hazard ratio (HR) and 95% confidence interval (CI). All statistical analyses were assessed by two authors independently.ResultA total of 13 studies were included in this study, including 824 postoperative adjuvant transarterial chemoembolization (pa-TACE) patients, 90 postoperative radiotherapy patients, 57 radiofrequency ablation (RFA)/re-resection patients, 16 sorafenib patients and 886 postoperative conservative treatment patients. The results showed that pa-TACE significantly improved OS and RFS compared with postoperative conservative treatment in patients with HCC with MVI after curative resection (HR: 0.64, 95% CI: 0.55–0.74, p ConclusionCompared with postoperative conservative treatment, pa-TACE, postoperative radiotherapy and sorafenib can improve the prognosis of patients with hepatocellular carcinoma with microvascular invasion after curative resection. Postoperative radiotherapy can reduce the recurrence of patients with HCC with MVI after curative resection compared with pa-TACE.

Background: Liver hepatocellular carcinoma (LIHC) is one of the most common malignant cancers worldwide, the overall prognosis of LIHC remains unsatisfactory. Valuable prognostic biomarkers are still urgently needed for LIHC. This study aimed to explore hub genes associated with the prognosis of LIHC and tumor microenvironmental immune infiltration, providing potential prognostic biomarker and therapeutic target for LIHC. Methods: RNA-seq counts data for LIHC samples were obtained from TCGA database. RNA-seq counts data for normal liver samples were obtained from GTEx database. Weighted gene co-expression network analysis (WGCNA) was used to cluster differentially expressed genes with similar expression profiles to form modules and significant modules and key genes were screened. Next, these genes was verified by cox analyses and overall survival analysis. Further, CIBERSORT was used to explore the relationship between these genes and tumor infiltrating immune cells. Results: A total number of 2661 significant DEGs were included for consensus WGCNA analysis, which identified 6 modules. Blue module (r=0.85, p CDC20, CDCA5, CDCA8, KIF2C and KIFC1 were identified as five potential marker genes, which would result in an unfavorable prognosis in LIHC. Further CIBERSORT analysis showed these novel biomarkers expression levels in LIHC were positively correlated with activated memory CD4+ T cells, follicular helper T cells, regulatory T cells and macrophages M0. While, resting memory CD4+ T cells, monocytes, macrophages M2, resting mast cells showed a negative correlation with the 5 novel biomarkers expression levels. Conclusions: The study screened 5 genes with marked prognostic capability for LIHC and found these genes were correlated with the infiltration of immune cells in LIHC tumor microenvironment. The findings might provide a more detailed molecular mechanism underlying LIHC occurrence and progression, holding promise for acting as potential biomarkers and therapeutic targets.

BDH2 is a short-chain dehydrogenase/reductase family member involved in several biological and pathological processes, including the utilization of cytosolic ketone bodies, immunocyte regulation and tumor progression. In this study, we first revealed that BDH2 was downregulated in HCC tissues by qRT-PCR and immunohistochemistry analysis and that low BHD2 expression was significantly associated with poor overall survival, poor tumor differentiation, increased tumor size, venous invasion and an advanced BCLC stage. Moreover, the results of a univariate analysis and multivariate analysis revealed that BDH2 may be regarded as an independent prognostic marker. As a member of a gene family involved in ketone metabolism, BDH2 upregulated the level of β-HB in liver cells as well as the level of H3 histone acetylation. Functional analysis showed that BDH2 expression inhibited tumor cell growth, proliferation and migration. The results of the mechanistic analysis revealed that BDH2 induced mitochondrial apoptosis and inhibited autophagy through the unfolded protein response. Therefore, BDH2 may be a new HCC prognostic marker and a useful treatment target.