scholarly journals Upregulated Seizure-Related 6 Homolog-Like 2 Is a Prognostic Predictor of Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Linhe Wang ◽  
Xiangchao Ling ◽  
Caihui Zhu ◽  
Zhiheng Zhang ◽  
Ziming Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Prognostic Predictor ◽  
Qrt Pcr ◽  
Cancer Genome Atlas

Seizure-related 6 homolog-like 2 (SEZ6L2), which is localized on the cell surface, has been found to be associated with tumor angiogenesis and lung cancer progression. However, the role of SEZ6L2 in hepatocellular carcinoma (HCC) is still unclear. We obtained data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to investigate SEZ6L2 expression and regulation in HCC. Then, HCC tissue samples were collected to verify SEZ6L2 by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining (IHC). Patient information was collected for survival and prognosis analysis. qRT-PCR, IHC, and bioinformatics analysis showed that the SEZ6L2 protein was highly expressed in HCC samples. Clinical data showed that high SEZ6L2 protein expression was correlated with tumor-node-metastasis (TNM) stages (P=0.046), tumor number (P=0.016), and tumor size (P=0.029). Meanwhile, SEZ6L2 overexpression was closely associated with poor overall survival and disease-free survival in HCC patients. Moreover, SEZ6L2 is an independent prognostic predictor for the survival of HCC patients. This study suggests a significant correlation between SEZ6L2 and HCC, which means that SEZ6L2 may potentially serve as a useful prognostic biomarker for HCC patients.

scholarly journals LncRNA DLGAP1-AS2 Overexpression Associates with Gastric Tumorigenesis; A Promising Diagnostic and Therapeutic Target

2021 ◽  
Author(s):  
Rogayeh Soltani ◽  
Mohammad Amini ◽  
Marziyeh Mazaheri Moghaddam ◽  
Asiyeh Jebelli ◽  
Sahar Ahmadiyan ◽  
...  
Keyword(s):  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Roc Curve Analysis ◽  
Aberrant Expression ◽  
Tissue Samples ◽  
Downstream Target ◽  
Qrt Pcr ◽  
Cancer Genome Atlas ◽  
Prostate Cancers

Abstract Background: Aberrant expression of long noncoding RNAs (lncRNAs) is associated with the progression of human cancers, including gastric cancer (GC). The function of lncRNA DLGAP1-AS2, as an oncogene, has been identified in glioma, hepatocellular carcinoma, and cholangiocarcinoma but not in other malignancies. Therefore, this study was aimed to explore the association of DLGAP1-AS2 with gastric tumorigenesis and beyond.Methods and Results: The expression level of DLGAP1-AS2 was prevaluated in GC datasets from Gene Expression Omnibus (GEO). Moreover, qRT-PCR experiment was performed on 25 paired GC and adjacent normal tissue samples. The Cancer Genome Atlas (TCGA) data were also analyzed for further validations. Consistent with data obtained from GEO datasets, qRT-PCR results revealed that DLGAP1-AS2 was significantly (p < 0.0032) upregulated in GC specimens compared to normal samples, which was additionally confirmed using TCGA analysis (p<0.0001). DLGAP1-AS2 expression level was also correlated with age (p =0.0008), lymphatic and vascular invasion (p =0.0415) in internal samples. Also, a significant correlation was found between DLGAP1-AS2 and YAP1 expression, as its valid downstream target, in GC samples. Besides, analysis of other prevalent tumor entities using TCGA illustrated the significant overexpression of DLGAP1-AS2 in lung, colorectal, and prostate cancers, further indicating its promise as an oncogene. Moreover, ROC curve analysis showed the high accuracy of the DLGAP1-AS2 expression pattern as a diagnostic biomarker for gastric and colorectal cancers. Conclusion: Our findings indicated that DLGAP1-AS2 might display oncogenic property in gastric tumorigenesis and be suggested as a therapeutic and diagnostic target.

scholarly journals Comprehensive analyses of competing endogenous RNA networks reveal potential biomarkers for predicting hepatocellular carcinoma recurrence

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ping Yan ◽  
Zuotian Huang ◽  
Tong Mou ◽  
Yunhai Luo ◽  
Yanyao Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
Clinical Information ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
High Rate ◽  
Competing Endogenous Rna ◽  
Tissue Samples ◽  
Potential Biomarkers

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors, with a high rate of recurrence worldwide. This study aimed to investigate the mechanism underlying the progression of HCC and to identify recurrence-related biomarkers. Methods We first analyzed 132 HCC patients with paired tumor and adjacent normal tissue samples from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). The expression profiles and clinical information of 372 HCC patients from The Cancer Genome Atlas (TCGA) database were next analyzed to further validate the DEGs, construct competing endogenous RNA (ceRNA) networks and discover the prognostic genes associated with recurrence. Finally, several recurrence-related genes were evaluated in two external cohorts, consisting of fifty-two and forty-nine HCC patients, respectively. Results With the comprehensive strategies of data mining, two potential interactive ceRNA networks were constructed based on the competitive relationships of the ceRNA hypothesis. The ‘upregulated’ ceRNA network consists of 6 upregulated lncRNAs, 3 downregulated miRNAs and 5 upregulated mRNAs, and the ‘downregulated’ network includes 4 downregulated lncRNAs, 12 upregulated miRNAs and 67 downregulated mRNAs. Survival analysis of the genes in the ceRNA networks demonstrated that 20 mRNAs were significantly associated with recurrence-free survival (RFS). Based on the prognostic mRNAs, a four-gene signature (ADH4, DNASE1L3, HGFAC and MELK) was established with the least absolute shrinkage and selection operator (LASSO) algorithm to predict the RFS of HCC patients, the performance of which was evaluated by receiver operating characteristic curves. The signature was also validated in two external cohort and displayed effective discrimination and prediction for the RFS of HCC patients. Conclusions In conclusion, the present study elucidated the underlying mechanisms of tumorigenesis and progression, provided two visualized ceRNA networks and successfully identified several potential biomarkers for HCC recurrence prediction and targeted therapies.

scholarly journals LncRNA SNHG17 Contributes to Proliferation, Migration, and Poor Prognosis of Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yue Luo ◽  
Junhao Lin ◽  
Jiakang Zhang ◽  
Zhenghui Song ◽  
Dayong Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Rna Sequencing ◽  
Expression Pattern ◽  
Cell Lines ◽  
Disease Free Survival ◽  
Loss Of Function ◽  
Poor Overall Survival ◽  
Apoptotic Pathway ◽  
Qrt Pcr

Long noncoding RNAs (lncRNAs) have been substantially reported to have critical roles in regulating tumorigenesis in recent years. However, the expression pattern and biological function of SNHG17 in hepatocellular carcinoma (HCC) remain unclear. Bioinformatics analysis and qRT-PCR were performed to detect the expression pattern of SNHG17 in HCC tissues, adjacent nontumorous tissues, and cell lines. The effect of SNHG17 on proliferation, migration, and apoptosis of HCC was investigated by knockdown and overexpressing SNHG17 in HCC cell lines. RNA sequencing was utilized to explore the underlying mechanism. Utilizing publicly available TCGA-LIHC, GSE102079 HCC datasets, and qRT-PCR, we found SNHG17 was significantly upregulated in HCC tissues and cell lines and was notably associated with larger tumor size, poorly differentiation, presence of vascular invasion, and advanced TNM stage. Furthermore, gain- and loss-of-function studies demonstrated that SNHG17 promoted cell proliferation and migration and inhibited apoptosis of HCC. By employing RNA sequencing, we found knockdown of SNHG17 caused 1037 differentially expressed genes, highly enriched in several pathways, including metabolic, PI3K-Akt, cell adhesion, regulation of cell proliferation, and apoptotic pathway; among them, 92 were overlapped with SNHG17-related genes in the TCGA-LIHC dataset. Furthermore, ERH, TBCA, TDO2, and PDK4 were successfully validated and found significantly dysregulated in HCC tissues. Moreover, HCC patients with higher SNHG17 expression had a relatively poor overall survival and disease-free survival, and ERH and PDK4 also played a marked role in the prognosis of HCC. Broadly, our findings illustrate that SNHG17 acts as a noncoding oncogene in HCC progression, suggesting its potential value as a novel target for HCC therapy.

scholarly journals High Squalene Epoxidase in Tumors Predicts Worse Survival in Patients With Hepatocellular Carcinoma: Integrated Bioinformatic Analysis on NAFLD and HCC

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482091466
Author(s):  
Tingting Shen ◽  
Yunfei Lu ◽  
Qin Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Messenger Rna ◽  
Disease Free Survival ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Squalene Epoxidase ◽  
Nonalcoholic Fatty Liver ◽  
Kaplan Meier ◽  
High Level

This study aimed to identify candidate biomarkers for predicting outcomes in nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Using Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) databases, we identified common upregulated differential expressed genes (DEGs) in patients with NAFLD/nonalcoholic steatohepatitis (NASH) and HCC and conducted survival analysis of these upregulated DEGs with HCC outcomes. Two common upregulated DEGs including squalene epoxidase (SQLE) and EPPK1 messenger RNA (mRNA) were significantly upregulated in NAFLD, NASH, and HCC tissues, both in GSE45436 ( P < .001) and TCGA profile ( P < .001). Both SQLE and EPPK1 mRNA were upregulated in 15.56% and 8.06% patients with HCC in TCGA profile. Overexpression of SQLE in tumors was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in patients with HCC (log-rank P = .027 and log-rank P = .048, respectively), while no statistical significances of OS and DFS were found in EPPK1 groups (both log-rank P > .05). For validation, SQLE upregulation contributed to significantly worse OS in patients wih HCC using Kaplan-Meier plotter analysis (hazard ratio = 1.43, 95% confidence interval: 1.01-2.02, log-rank P = .043). In addition, high level of SQLE significantly associated with advanced neoplasm histologic grade, advanced AJCC stage, and α-fetoprotein elevation ( P = .036, .045, and .029, respectively). Squalene epoxidase is associated with OS and DFS and serves as a novel prognostic biomarker for patients with HCC.

scholarly journals Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu Pan ◽  
Geng-yuan Hu ◽  
Shi Jiang ◽  
Shun-jie Xia ◽  
Hendi Maher ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Aerobic Glycolysis ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Sorafenib Therapy ◽  
Tumor Tissues ◽  
Cancer Genome Atlas ◽  
Advanced Stages ◽  
Disease Free

Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.

scholarly journals Thymosin β 10 is overexpressed and associated with unfavorable prognosis in hepatocellular carcinoma

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Chunrong Song ◽  
Zhong Su ◽  
Jing Guo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Human Cancer ◽  
Normal Liver ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Tumor Biomarker ◽  
Advanced Tumor Stage ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Advanced Tumor

Abstract Thymosin β 10 (TMSB10) has been demonstrated to be overexpressed and function as an oncogene in most types of human cancer including hepatocellular carcinoma (HCC). In our study, we present more evidence about the clinical significance and biological function of TMSB10 in HCC. First, we observed levels of TMSB10 expression were obviously increased in HCC tissues compared with normal liver tissues at The Cancer Genome Atlas (TCGA) datasets. Furthermore, we confirmed that TMSB10 mRNA and protein levels were also increased in HCC tissue samples compared with normal adjacent normal liver tissue samples. In addition, we found high TMSB10 expression was remarkably associated with the advanced tumor stage, large tumor size, distant metastasis, and poor prognosis, and acted as an independent factor for predicting poor overall survival in HCC patients. Loss-of-function studies suggested silencing of TMSB10 expression dramatically reduced cell proliferation, migration, and invasion in HCC. In conclusion, TMSB10 may hold promise as a tumor biomarker for predicting prognosis and a potential target for developing a novel therapeutic strategy.

scholarly journals The Oncogenic Role of CENPA in Hepatocellular Carcinoma Development: Evidence from Bioinformatic Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuan Zhang ◽  
Lei Yang ◽  
Jia Shi ◽  
Yunfei Lu ◽  
Xiaorong Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Tcga Dataset ◽  
High Level

Objective. This study is aimed at investigating the predictive value of CENPA in hepatocellular carcinoma (HCC) development. Methods. Using integrated bioinformatic analysis, we evaluated the CENPA mRNA expression in tumor and adjacent tissues and correlated it with HCC survival and clinicopathological features. A Cox regression hazard model was also performed. Results. CENPA mRNA was significantly upregulated in tumor tissues compared with that in adjacent tissues, which were validated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) series (all P<0.01). In the Kaplan-Meier plotter platform, the high level of CENPA mRNA was significantly correlated with overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), and progression-free survival (PFS) in HCC patients (all log rank P<0.01). For validation in GSE14520 and pan-TCGA dataset, HCC patients with CNEPA mRNA overexpression had poor OS compared with those with low CENPA mRNA (log rank P=0.025 and P<0.0001, respectively), and those with high CENPA had poor DFS in TCGA (log rank P=0.0001). Additionally, CENPA mRNA were upregulated in HCC patients with alpha-fetoprotein (AFP) elevation, advanced TNM stage, larger tumor size, advanced AJCC stage, advanced pathology grade, and vascular invasion (all P<0.05). A Cox regression model including CENPA, OIP5, and AURKB could predict OS in HCC patients effectively (AUC=0.683). Conclusion. Overexpressed in tumors, CENPA might be an oncogenic factor in the development of HCC patients.

scholarly journals MicroRNA-497-5p Is Downregulated in Hepatocellular Carcinoma and Associated with Tumorigenesis and Poor Prognosis in Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Lin-Lin Tian ◽  
Bin Qian ◽  
Xiao-Hui Jiang ◽  
Yu-Shan Liu ◽  
Tong Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Target Genes ◽  
Progression Free Survival ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Tumor Diameter ◽  
Expression Levels

Background. MicroRNAs (miRNAs) have been demonstrated to exhibit important regulatory roles in multiple malignancies, including hepatocellular carcinoma (HCC). hsa-miR-497-5p was reported to involve in cancer progression and poor prognosis in many kinds of tumors. However, the expression and its clinical significance of hsa-miR-497-5p in HCC remain unclear. Methods. In the present study, we investigated the expression of hsa-miR-497-5p in HCC and analyzed the correction of clinical features with prognosis. The expression levels of hsa-miR-497-5p and potential target genes were analyzed in HCC and adjacent noncancerous tissues using The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze hsa-miR-497-5p levels in 328 HCC tissues and 30 paired adjacent noncancer tissues. Overall survival (OS) and progression-free survival (PFS) of patients with HCC were assessed using the Kaplan-Meier method and the log-rank test. Results. The hsa-miR-497-5p expression levels were decreased, and its target genes ACTG1, CSNK1D, PPP1CC, and BIRC5 were upregulated in HCC tissues compared with normal tissues. Lower levels of hsa-miR-497-5p expression and higher levels of the four target genes were significantly associated with higher tumor diameter. Moreover, patients with lower hsa-miR-497-5p expression and higher target genes levels had shorter OS. Conclusion. The expression levels of hsa-miR-497-5p may play an important regulatory role in HCC and are closely correlated with HCC progression and poor prognosis in patients. The hsa-miR-497-5p may be a specific therapeutic target for the treatment of HCC.

scholarly journals High Vimentin Expression Predicts a Poor Prognosis and Progression in Colorectal Cancer: A Study with Meta-Analysis and TCGA Database

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Le Du ◽  
Jingchuan Li ◽  
Lei Lei ◽  
Hongjuan He ◽  
Erfei Chen ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Poor Overall Survival ◽  
Vimentin Expression ◽  
Cancer Genome Atlas ◽  
N Stage

The aim of this study was to evaluate the role of vimentin expression in the prognosis and progression of CRC. Meta-analysis was conducted to investigate the correlations between vimentin and prognosis and clinicopathological features in CRC. Literatures were searched by PubMed, Embase, ClinicalKey, CNKI, VIP, and WanFang databases. The Cancer Genome Atlas (TCGA) database was used to assess the association of vimentin expression with survival rate in CRC. Eleven reports with 1969 cases were included in the meta-analysis. The results showed that positive vimentin expression predicted a poor overall survival (OS) in the univariate analysis (HR: 2.087, 95%CI: 1.660-2.625) and multivariate analysis (HR: 1.633, 95%CI: 1.223-2.181). Vimentin overexpression also conferred worse disease-free survival (DFS) in the univariate analysis (HR: 2.069, 95%CI: 1.024-4.179) and multivariate analysis (HR: 2.802, 95%CI: 1.421-5.527). Moreover, upregulated vimentin is related to lymph node metastasis (OR: 2.288, 95%CI: 1.159-4.517), TNM stages (OR: 1.957, 95%CI: 1.333-2.873), and N stage (OR: 2.316, 95%CI: 1.482-3.620). Analysis of TCGA database indicated that elevated vimentin predicated a shorter OS (p=0.033). Our findings reveal that upregulated vimentin contributes to the progression and poor prognosis of CRC. Vimentin may be a prognostic biomarker and therapeutic target in patients with CRC.

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