Identification of Potential Prognostic Long Non-Coding RNA Biomarkers for Predicting Survival in Patients with Hepatocellular Carcinoma.

BACKGROUND/AIMS: The aim of the current study was to identify potential prognostic long non-coding RNA (lncRNA) biomarkers for predicting survival in patients with hepatocellular carcinoma (HCC) using The Cancer Genome Atlas (TCGA) dataset and bioinformatics analysis. METHODS: RNA sequencing and clinical data of HCC patients from TCGA were used for prognostic association assessment by univariate Cox analysis. A prognostic signature was built using stepwise multivariable Cox analysis, and a comprehensive analysis was performed to evaluate its prognostic value. The prognostic signature was further evaluated by functional assessment and bioinformatics analysis. RESULTS: Thirteen differentially expressed lncRNAs (DELs) were identified and used to construct a single prognostic signature. Patients with high risk scores showed a significantly increased risk of death (adjusted P < 0.0001, adjusted hazard ratio = 3.522, 95% confidence interval = 2.307-5.376). In the time-dependent receiver operating characteristic analysis, the prognostic signature performed well for HCC survival prediction with an area under curve of 0.809, 0.782 and 0.79 for 1-, 3- and 5-year survival, respectively. Comprehensive survival analysis of the 13-DEL prognostic signature suggested that it serves as an independent factor in HCC, showing a better performance for prognosis prediction than traditional clinical indicators. Functional assessment and bioinformatics analysis suggested that the prognostic signature was associated with the cell cycle and peroxisome proliferator-activated receptor signaling pathway. CONCLUSIONS: The novel lncRNA expression signature identified in the present study may be a potential biomarker for predicting the prognosis of HCC patients.

Does the Preoperative Depression Affect Clinical Outcomes in Adults With Following Lumbar Fusion?: A Retrospective Cohort Study.

STUDY DESIGN: This was a retrospective cohort review. OBJECTIVE: The objective of this study was to analyze depression using Beck Depression Inventory (BDI) and Hamilton Depression Scale (HAMD-24), and to correlate with clinical outcomes and improvement in adults with following lumbar fusion. SUMMARY OF BACKGROUND DATA: Psychological factors such as depression are found to influence outcomes and improvement following spinal surgery. It is still unclear whether there are differences during screening for depression by different implementations to predict outcomes for spine surgery. MATERIALS AND METHODS: Between July 2016 and May 2018, patients with degenerative lumbar disease, who underwent lumbar fusion were enrolled in this study. The patient's characteristics, preoperative BDI and HAMD-24 score, and preoperative and postoperative outcomes were collected, respectively. Depressed patients were identified by a score of BDI≥15 or HAMD-24>20, respectively. Preoperative and postoperative outcome scores, absolute changes, and recovery ratios of disability and pain were compared within and between groups. Finally, univariate and multiple linear regression analyses was performed to reveal the relationship between preoperative depressive states and outcomes and improvement. RESULTS: A total of 125 patients were eligible in the study, with 113 (90.4%) patients without depressive symptoms and 12 (9.6%) depressed patients by BDI, and 97 (77.6%) patients without depressive symptoms and 28 (22.4%) depressed patients by HAMD-24. Both higher BDI and HAMD-24 group was found to have significant worse preoperative and postoperative outcomes as well as less recovery ratios than the patients without depressive symptoms. Univariate and multiple linear regression analyses suggested that preoperative depression might be a potential predictor of worse surgical outcomes. CONCLUSIONS: Depressive symptoms might lead to smaller magnitude of improvement. Moreover, both preoperative BDI and HAMD-24 score was a negative predictor of postoperative outcomes and can be regarded as a candidate to screen for depression preoperatively.

Comprehensive investigation of key biomarkers and pathways in hepatitis B virus-related hepatocellular carcinoma.

Objective: Our study is aim to explore potential key biomarkers and pathways in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using genome-wide expression profile dataset and methods. Methods: Dataset from the GSE14520 is used as the training cohort and The Cancer Genome Atlas dataset as the validation cohort. Differentially expressed genes (DEGs) screening were performed by the limma package. Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), gene ontology, the Kyoto Encyclopedia of Genes and Genomes, and risk score model were used for pathway and genes identification. Results: GSEA revealed that several pathways and biological processes are associated with hepatocarcinogenesis, such as the cell cycle, DNA repair, and p53 pathway. A total of 160 DEGs were identified. The enriched functions and pathways of the DEGs included toxic substance decomposition and metabolism processes, and the P450 and p53 pathways. Eleven of the DEGs were identified as hub DEGs in the WGCNA. In survival analysis of hub DEGs, high expression of PRC1 and TOP2A were significantly associated with poor clinical outcome of HBV-related HCC, and shown a good performance in HBV-related HCC diagnosis. The prognostic signature consisting of PRC1 and TOP2A also doing well in the prediction of HBV-related HCC prognosis. The diagnostic and prognostic values of PRC1 and TOP2A was confirmed in TCGA HCC patients. Conclusions: Key biomarkers and pathways identified in the present study may enhance the comprehend of the molecular mechanisms underlying hepatocarcinogenesis. Additionally, mRNA expression of PRC1 and TOP2A may serve as potential diagnostic and prognostic biomarkers for HBV-related HCC.

Integrated analysis of competing endogenous RNA network revealing potential prognostic biomarkers of hepatocellular carcinoma.

Objective: The goal of our study is to identify a competing endogenous RNA (ceRNA) network using dysregulated RNAs between HCC tumors and the adjacent normal liver tissues from The Cancer Genome Atlas (TCGA) datasets, and to investigate underlying prognostic indicators in hepatocellular carcinoma (HCC) patients. Methods: All of the RNA- and miRNA-sequencing datasets of HCC were obtained from TCGA, and dysregulated RNAs between HCC tumors and the adjacent normal liver tissues were investigated by DESeq and edgeR algorithm. Survival analysis was used to confirm underlying prognostic indicators. Results: In the present study, we constructed a ceRNA network based on 16 differentially expressed genes (DEGs), 7 differentially expressed microRNAs and 34 differentially expressed long non-coding RNAs (DELs). Among these dysregulated RNAs, three DELs (AP002478.1, HTR2A-AS1, and ERVMER61-1) and six DEGs (enhancer of zeste homolog 2 [EZH2], kinesin family member 23 [KIF23], chromobox 2 [CBX2], centrosomal protein 55 [CEP55], cell division cycle 25A [CDC25A], and claspin [CLSPN]) were used for construct a prognostic signature for HCC overall survival (OS), and performed well in HCC OS (adjusted P<0.0001, adjusted hazard ratio = 2.761, 95% confidence interval = 1.838-4.147). Comprehensive survival analysis demonstrated that this prognostic signature may be act as an independent prognostic indicator of HCC OS. Functional assessment of these dysregulated DEGs in the ceRNA network and gene set enrichment of this prognostic signature suggest that both were enriched in the biological processes and pathways of the cell cycle, cell division and cell proliferation. Conclusions: Our current study constructed a ceRNA network for HCC, and developed a prognostic signature that may act as an independent indicator for HCC OS.

Genetic variants and Expression of Cytochrome p450 Oxidoreductase Predict Postoperative Survival in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma.

Our current study investigates the prognostic values of genetic variants and mRNA expression of cytochrome p450 oxidoreductase (POR) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A total of 19 candidate single nucleotide polymorphisms (SNPs) located in the exons of POR were genotyped using Sanger sequencing from 476 HBV-related HCC patients who underwent hepatectomy between 2003 and 2013. The mRNA expression of POR in 212 patients with HBV-related HCC was obtained from GSE14520 dataset. Survival analysis was performed to investigate the association of POR variants and mRNA expression with overall survival (OS) and recurrence-free survival (RFS). Nomograms were used to predict the prognosis of HBV-related HCC patients. Gene set enrichment analysis (GSEA) was used to investigate the mechanism of POR in HBV-related HCC prognosis. The polymorphism POR-rs1057868 was significantly associated with HBV-related HCC OS (CT/TT vs. CC, hazard ratio [HR] = 0.69, 95% confidence interval [CI] = [0.54, 0.88], P = 0.003), but not significantly associated with RFS (CT/TT vs. CC, P = 0.378). POR mRNA expression was also significantly associated with HBV-related HCC OS (high vs. low, HR = 0.61, 95% CI = [0.38, 0.97], P = 0.036), but not significantly associated with the RFS (high vs. low, P = 0.201). Two nomograms were developed to predict the HBV-related HCC OS. Furthermore, GSEA suggests that multiple gene sets were significantly enriched in liver cancer survival and recurrence, as well as POR-related target therapy in the liver. In conclusion, our study suggests that POR-rs1057868 and mRNA expression may serve as a potential postoperative prognosis biomarker in HBV-related HCC.

Distinct Diagnostic and Prognostic Values of Minichromosome Maintenance Gene Expression in Patients with Hepatocellular Carcinoma.

Background: The aim of the present study was to identify diagnostic and prognostic values of minichromosome maintenance (MCM) gene expression in patients with hepatocellular carcinoma (HCC). Methods: The biological function of the MCM genes were investigated by bioinformatics analysis. The diagnostic and prognostic values of the MCM genes were investigated by using the data of HCC patients from the GSE14520 and The Cancer Genome Atlas (TCGA) databases. Results: Bioinformatics analysis of the MCM genes substantiated that MCM2-7 genes were significantly enriched in DNA replication and cell cycle, and co-expressed with each other. These genes also co-expressed in HCC tumor tissue in both the GSE14520 and TCGA cohort. We also observed that the expression of the MCM2-7 genes was increased in tumor tissue, and diagnostic receiver operating characteristic analysis of MCM2-7 indicated that these genes could serve as sensitive diagnostic markers in HCC. Survival analysis in the GSE14520 cohort suggested that expression of MCM2, MCM4, MCM5, and MCM6 were significantly associated with hepatitis B virus-related HCC overall survival (OS). However, none of the MCM genes were associated with recurrence-free survival in the GSE14520 cohort. The validation cohort of TCGA suggested that the expression of MCM2, MCM6, and MCM7 were significantly correlated with HCC OS. Conclusion: Our study indicated that MCM2-7 genes may be potential diagnostic biomarkers in patients with HCC. Among them, MCM2 and MCM6 may serve as potential prognostic biomarkers for HCC.

[Effectiveness comparison of flexible fixation and rigid fixation in treatment of ankle pronation-external rotation fractures with distal tibiofibular syndesmosis].

Objective: To compare the effectiveness of flexible fixation and rigid fixation in the treatment of ankle pronation-external rotation fractures with distal tibiofibular syndesmosis. Methods: A retrospective analysis was made on the clinical data of 50 patients with ankle pronation-external rotation fractures and distal tibiofibular syndesmosis treated between January 2013 and December 2015. Suture-button fixation was used in 23 patients (flexible fixation group) and cortical screw fixation in 27 patients (rigid fixation group). There was no significant difference in age, gender, weight, side, fracture type, and time from trauma to surgery between 2 groups ( P>0.05). The operation time, medial clear space (MCS), tibiofibular clear space (TFCS), tibiofibular overlap (TFO), American Orthopaedic Foot and Ankle Society (AOFAS) score, and Foot and Ankle Disability Index (FADI) score were compared between 2 groups. Results: The operation time was (83.0±9.1) minutes in the flexible fixation group and was (79.6±13.1) minutes in the rigid fixation group, showing no significant difference ( t=1.052, P=0.265). All patients achieved healing of incision by first intention. The patients were followed up 12-20 months (mean, 14 months). The X-ray films showed good healing of fracture in 2 groups. There was no screw fracture, delayed union or nounion. The fracture healing time was (12.1±2.5) months in the flexible fixation group and was (11.3±3.2) months in the rigid fixation group, showing no significant difference between 2 groups ( t=1.024, P=0.192). Reduction loss occurred after removal of screw in 2 cases of the rigid fixation group. At last follow-up, there was no significant difference in MCS, TFCS, TFO, AOFAS score and FADI score between 2 groups ( P>0.05). Conclusion: Suture-button fixation has similar effectiveness to screw fixation in ankle function and imaging findings, and flexible fixation has lower risk of reduction loss of distal tibiofibular syndesmosis than rigid fixation.