Hypoxia is a universal feature in the tumor microenvironment (TME). Nonetheless, the heterogeneous hypoxia patterns of TME have still not been elucidated in hepatocellular carcinoma (HCC). Using consensus clustering algorithm and public datasets, we identified heterogeneous hypoxia subtypes. We also revealed the specific biological and clinical characteristics via bioinformatic methods. The principal component analysis algorithm was employed to develop a hypoxia-associated risk score (HARS). We identified the two hypoxia subtypes: low hypoxia pattern (C1) and high hypoxia pattern (C2). C1 was less sensitive to immunotherapy compared to C2, consistent with the lack of immune cells and immune checkpoints (ICPs) in C1, whereas C2 was the opposite. C2 displayed worse prognosis and higher sensitivity to obatoclax relative to C1, while C1 was more sensitive to sorafenib. The two subtypes also demonstrated subtype-specific genomic variations including mutation, copy number alteration, and methylation. Moreover, we developed and validated a risk signature: HARS, which had excellent performance for predicting prognosis and immunotherapy. We revealed two hypoxia subtypes with distinct biological and clinical characteristics in HCC, which enhanced the understanding of hypoxia pattern. The risk signature was a promising biomarker for predicting prognosis and immunotherapy.

Purpose: To evaluate the method and effectiveness of transcatheter arterial chemoembolization (TACE) combined with simultaneous DynaCT-guided Microwave ablation (MWA) for the treatment of small hepatocellular carcinoma (SHCC). Materials and methods: From June 2015 to May 2017, a total of 28 consecutive patients with SHCC received single treatment of TACE and 23 subjects received a combination treatment of TACE with simultaneous DynaCT-guided MWA. Following 1 month of treatment, the tumor response was assessed using the mRECIST criteria and the outcomes were analyzed including intervention-associated complications, changes in liver function, imaging response, and progression-free survival (PFS). Results: The technical success rate was 100%. The rates of CR (65%) in the combined TACE and MWA group were higher than those of the TACE group (46%). The rate of common adverse events, such as liver abscess, spontaneous bacterial peritonitis and liver dysfunction, in the combined TACE and MWA group (56%) was comparable to the corresponding rate of the TACE group (P > 0.411). The median and mean PFS of the TACE group were significantly lower than those of the combined TACE and MWA group (19.00 months vs. 29.00 months, 21.076 months vs. 24.693 months, p = 0.019, log-rank test). Conclusion: Stereotactic DynaCT-guided MWA is a safe and effective method for the treatment of SHCC, which usually provides an effective tumor puncture path, notably for lesions that cannot be detected following TACE. Overall, the data suggested that this treatment method could improve the clinical outcome of patients with SHCC.

Accumulating evidence has demonstrated that microRNAs (miRNAs or miRs) play an important role in the diagnosis and prognosis of tumors. In the case of cholangiocarcinoma (CCA), miRNAs may serve as potential tumor biomarkers and therapeutic targets. Based on The Cancer Genome Atlas (TCGA) database, fold change >2 was used to screen out miRNAs with differential expression in patients with CCA. Univariate and multivariate Cox regression analyses identified miR‐3913‐5p as an independent prognostic factor in patients with CCA. Overall survival and progression‐free survival of patients with CCA were analyzed based on clinical data from TCGA database. In addition, four datasets were combined to identify 21 possible target genes of miR‐3913, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to predict potential pathways and functions of the molecular target genes. Subsequently, the miRNAs associated with survival were selected to build the miRNA‐mRNA expression network. Furthermore, the differential expression of miR‐3913‐5p in CCA cells and normal bile duct epithelial cells was confirmed through in vitro experiments. The possible target genes (RNF24 and SIGLEC) were further screened by reverse transcription‐quantitative PCR. In addition, functional experiments showed that miR‐3913‐5p might be an oncogene that affects the proliferation and migration of CCA cells by inhibiting and mimicking miR‐3913‐5p. Therefore, miR‐3913 may serve as a biomarker for the diagnosis and prognosis of patients with CCA.

Background. Hepatocellular carcinoma (HCC) remains an important cause of cancer death. The molecular mechanism of hepatocarcinogenesis and prognostic factors of HCC have not been completely uncovered. Methods. In this study, we screened out differentially expressed lncRNAs (DE lncRNAs), miRNAs (DE miRNAs), and mRNAs (DE mRNAs) by comparing the gene expression of HCC and normal tissue in The Cancer Genome Atlas (TCGA) database. DE mRNAs were used to perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then, the miRNA and lncRNA/mRNA modules that were most closely related to the survival time of patients with HCC were screened to construct a competitive endogenous RNA (ceRNA) network by weighted gene coexpression network analysis (WGCNA). Moreover, univariable Cox regression and Kaplan-Meier curve analyses of DE lncRNAs and DE mRNAs were conducted. Finally, the lasso-penalized Cox regression analysis and nomogram model were used to establish a new risk scoring system and predict the prognosis of patients with liver cancer. The expression of survival-related DE lncRNAs was verified by qRT-PCR. Results. A total of 1896 DEmRNAs, 330 DElncRNAs, and 76 DEmiRNAs were identified in HCC and normal tissue samples. Then, the turquoise miRNA and turquoise lncRNA/mRNA modules that were most closely related to the survival time of patients with HCC were screened to construct a ceRNA network by WGCNA. In this ceRNA network, there were 566 lncRNA-miRNA-mRNA regulatory pairs, including 30 upregulated lncRNAs, 16 downregulated miRNAs, and 75 upregulated mRNAs. Moreover, we screened out 19 lncRNAs and 14 hub mRNAs related to prognosis from this ceRNA network by univariable Cox regression and Kaplan-Meier curve analyses. Finally, a new risk scoring system was established by selecting the optimal risk lncRNAs from the 19 prognosis-related lncRNAs through lasso-penalized Cox regression analysis. In addition, we established a nomogram model consisting of independent prognostic factors to predict the survival rate of HCC patients. Finally, the correlation between the risk score and immune cell infiltration and gene set enrichment analysis were determined. Conclusions. In conclusion, the results may provide potential biomarkers or therapeutic targets for HCC and the establishment of the new risk scoring system and nomogram model provides the new perspective for predicting the prognosis of HCC.

Exosomes are vesicles with a diameter of 30‐150 nm produced by living cells and secreted into the extracellular matrix. Exosomes mediate cellular communication by carrying active molecules, such as nucleic acids, proteins, and liposomes. Although exosomes are found in various body fluids, little is known about bile‐derived exosomes. This review is the first to summarize the methods of bile storage and isolation of biliary exosomes, highlighting the roles of bile‐derived exosomes, especially exosomal noncoding RNAs, in physiological and disease states and discussing their potential clinical applications.

Purpose: The purpose of this study was to compare the safety and effectiveness of a self-expandable metallic stent (SEMs) with a novel brachytherapy biliary drainage catheter (BBDC, double ¹²⁵I seeds strands) or a single ¹²⁵I seeds strand in the treatment of advanced perihilar cholangiocarcinoma (pCCA) with malignant obstructive jaundice (MOJ). Methods: From September 2016 to December 2018, we retrospectively enrolled patients with biliary stent implantation after receiving either BBDC loaded with ¹²⁵I seeds (double-strands irradiation group) or an ¹²⁵I seed strand treatment (single-strand irradiation group, control group). The outcomes were analyzed regarding the relief of obstructive jaundice, and interventional-related complications. Moreover, the Kaplan–Meier method was used to analyze stent patency and survival. Results: The success rate of interventional therapy in both groups was 100%, and all patients with MOJ were alleviated. According to the Common Terminology Criteria for Adverse Events (CTCAE 4.02), the grade 3 or 4 complications in the BBDC group and in the control group were 6/34 (17.65%) and 7/39 (17.95%), respectively (P > 0.05). The median and mean overall stent patency of the BBDC group and the control group were 207 days versus 180 days, 204.212 days versus 186.278 days (P = 0.043). The median and mean overall survivals in the BBDC group were higher than those in the control group (245 days versus 212 days, 244.883 days versus 221.844 days, P = 0.030). Conclusion: This interim analysis showed that BBDC (double-stranded irradiation) can prolong the stent patency time compared with ¹²⁵I seed strand treatment (single-stranded irradiation) and had the advantage of reducing jaundice, which seemed to extend the survival period of advanced pCCA.