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 ◽  
...  

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.

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1523
Author(s):  
Huimin Li ◽  
Longxiang Xie ◽  
Qiang Wang ◽  
Yifang Dang ◽  
Xiaoxiao Sun ◽  
...  

Myxofibrosarcoma is a complex genetic disease with poor prognosis. However, more effective biomarkers that forebode poor prognosis in Myxofibrosarcoma remain to be determined. Herein, utilizing gene expression profiling data and clinical follow-up data of Myxofibrosarcoma cases in three independent cohorts with a total of 128 Myxofibrosarcoma samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we constructed an easy-to-use web tool, named Online consensus Survival analysis for Myxofibrosarcoma (OSmfs) to analyze the prognostic value of certain genes. Through retrieving the database, users generate a Kaplan–Meier plot with log-rank test and hazard ratio (HR) to assess prognostic-related genes or discover novel Myxofibrosarcoma prognostic biomarkers. The effectiveness and availability of OSmfs were validated using genes in ever reports predicting the prognosis of Myxofibrosarcoma patients. Furthermore, utilizing the cox analysis data and transcriptome data establishing OSmfs, seven genes were selected and considered as more potentially prognostic biomarkers through overlapping and ROC analysis. In conclusion, OSmfs is a promising web tool to evaluate the prognostic potency and reliability of genes in Myxofibrosarcoma, which may significantly contribute to the enrichment of novelly potential prognostic biomarkers and therapeutic targets for Myxofibrosarcoma.


2021 ◽  
Author(s):  
Jianting Du ◽  
Li-rong Xiao ◽  
Guobing Xu ◽  
Bin Zheng ◽  
Chun Chen

Abstract Background: Esophageal cancer (ESCA) is one of the most aggressive and lethal human malignant cancers. It is associated with poor overall survival (OS) and ranks sixth among the causes of cancer-related mortalities. MiR-1301-3p plays vital roles in a majority of malignancies. The aim of this study was to investigate the correlation between miR-1301-3p/NBL1 axis and prognosis of ESCA patients.Methods: We compared the miR-1301-3p expression levels between ESCA and normal esophageal tissues using MiRNAseq data retrieved from The Cancer Genome Atlas (TCGA) database. We employed UALCAN web platform, starBase v3.0 database, R software and GEPIA web platform to perform statistical analysis and data visualization. We then used TargetScan Human, miRDB and DIANA Tools databases to predict the miR-1301-3p target genes. Finally, we analyzed the expression patterns of the target genes as well as their prognostic value in ESCA.Results: There was an overexpression of miR-1301-3p in most malignancies, including ESCA (P<0.001). The miR-1301-3p expression levels were significantly related to age and histologic grade in primary ESCA (P<0.05), with high expression of miR-1301-3p being significantly associated with poor prognosis (Hazard ratio [HR]=1.88, P=0.012). NBL1 was identified as a potential target gene for miR-1301-3p and a negatively correlation in expression levels between the two genes was observed (r=-0.282, P<0.001). Notably, NBL1 was significantly downregulated in ESCA (P<0.001) and its low expression was significantly associated with poor prognosis of ESCA patients (HR=0.53, P=0.0063).Conclusion: miR-1301-3p is a potential biomarker for predicting prognosis of ESCA patients. It may regulate ESCA progression by regulating NBL1 expression.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuan Zhang ◽  
Lei Yang ◽  
Jia Shi ◽  
Yunfei Lu ◽  
Xiaorong Chen ◽  
...  

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.


2020 ◽  
Vol 18 ◽  
pp. 205873922094614
Author(s):  
Hua-Li Zhu ◽  
Jing Zou

It is indicated that the dysregulation of long noncoding RNAs (lncRNAs) is implicated in cancer progression. However, the clinical significance of lncRNA small nucleolar RNA host gene 1 (SNHG1) in gastric cancer remains elusive. The expression levels of SNHGs and the association of SNHG1/10/11 with the clinical characteristics in patients with gastric cancer were analyzed by The Cancer Genome Atlas RNA-seq data. A Cox proportional hazard regression model was used to evaluate the association of SNHG1/10/11 expression with the clinical outcomes in patients with gastric cancer. It was demonstrated that SNHG1/10/11 expression levels were dramatically elevated in gastric cancer tissue samples as compared with the adjacent normal tissues. Increased expression of SNHG1 had no correlation with the clinicopathological parameters, but acted as an independent prognostic factor of poor survival (hazard ration (HR) = 0.590, 95% confidence interval (CI) = 0.399–0.872, P = 0.008) and tumor recurrence (HR = 2.457, 95% CI = 1.442–4.186, P = 0.001) in patients with gastric cancer. In addition, knockdown of SNHG1 in vitro inhibited the proliferation and invasion of gastric cancer cells. Our findings showed that the upregulation of lncRNA SNHG1 indicated a poor prognosis in patients with gastric cancer and might offer a promising therapeutic target for gastric cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Kainan Zhang ◽  
Hui Liu ◽  
Mengsi Yu ◽  
Hui Zhao ◽  
Ning Yang ◽  
...  

The development of hepatocellular carcinoma (HCC) is a complex pathological process. Long intergenic non–protein-coding RNA 1667 (LINC01667, also known as MGC38584) plays an oncogenic role in several human cancers; however, its functional role in HCC tumorigenesis remains unknown. Here, we first evaluated the gene expression levels of LINC01667 in HCC using data from The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We then elucidated the association between LINC01667 gene expression levels and the survival rates of patients with HCC. We detected the effect of LINC01667 on the malignant phenotypes (cell proliferation, migration, invasion and apoptosis etc.) and the MAPK and PI3K/AKT/mTOR signaling pathways of HepG2, SMMC-7721 and HUH7 cells. We also analyzed the sensitivity of HepG2, SMMC-7721 and HUH7 with different expression levels of LINC01667 to anti-HCC drugs in vitro. Based on data from the aforementioned databases and our experiments in vitro, we found that LINC01667 was overexpressed in HCC, and that patients with high LINC01667 levels had a remarkably poor overall survival rate. In addition, inhibition of LINC01667 expression suppressed the proliferation, migration and invasion of HepG2 and SMMC-7721 cells and promoted their apoptosis in vitro. In contrast, overexpression of LINC01667 promoted the proliferation, migration and invasion of HUH7 cells and suppressed their apoptosis in vitro. ChIRP-seq (chromatin isolation by RNA purification) showed that LINC01667 bound to MEG3, and downregulated the expression of MEG3. In addition, western blotting showed that LINC01667 could activate the NF-κB pathway to promote cancer progression. In conclusion, we report that LINC01667 is an important oncogene in HCC and may be used as a potential diagnostic and prognostic biomarker of HCC.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Linhe Wang ◽  
Xiangchao Ling ◽  
Caihui Zhu ◽  
Zhiheng Zhang ◽  
Ziming Wang ◽  
...  

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.


2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098064
Author(s):  
Junfeng Wang ◽  
Jianying Lou ◽  
Lei Fu ◽  
Qu Jin

Background Hepatocellular carcinoma (HCC) is a highly malignant tumor with a particularly poor prognosis. The tumor microenvironment (TME) is closely associated with tumorigenesis, progression, and treatment. However, the relationship between TME genes and HCC patient prognosis is poorly understood. Methods In this study, we identified two prognostic subtypes based on the TME using data from The Cancer Genome Atlas and Gene Expression Omnibus. The Microenvironment Cell Populations-counter method was used to evaluate immune cell infiltration in HCC. Differentially expressed genes between molecular subtypes were calculated with the Limma package, and clusterProfiler was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses to identify genes related to the independent subtypes. We also integrated mRNA expression data into our bioinformatics analysis. Results We identified 4227 TME-associated genes and 640 genes related to the prognosis of HCC. We defined two major subtypes (Clusters 1 and 2) based on the analysis of TME-associated gene expression. Cluster 1 was characterized by increased expression of immune-associated genes and a worse prognosis than Cluster 2. Conclusions The identification of these HCC subtypes based on the TME provides further insight into the molecular mechanisms and prediction of HCC prognosis.


2021 ◽  
Author(s):  
Mingxin Lin ◽  
Jingping Liu ◽  
Xiaoli Shi ◽  
Jiajun Li ◽  
Huiming Ye

Abstract Background: I kappa B kinase interacting protein (IKBIP) is dysregulated and closely correlated with prognosis in tumor. However, the potential functions of IKBIP have not been utterly revealed in hepatocellular carcinoma (HCC). Thus, we explored the clinical values of IKBIP and its correlation with immune infiltrates in HCC.Methods: IKBIP expression in different tumor types was analyzed through the Tumor Immunity Evaluation Resource (TIMER) database. IKBIP expression between HCC and normal tissues were readily available for retrospective analyses from GEPIA, UALCAN and the Cancer Genome Atlas (TCGA) databases. The association between clinical features and IKBIP expression in HCC was analyzed by the Wilcoxon signed-rank test and logistic regression. Human Protein Atlas (HPA) was used to analyze the protein expression of IKBIP. A receiver operating characteristic (ROC) curve was performed to explore diagnostic potential of IKBIP. Kaplan-Meier (K-M) method and Cox regression were conducted to evaluate the influence of IKBIP on the prognosis of HCC patients. Protein-protein interaction (PPI) networks were established using STRING. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for gene functional enrichment analysis. The interrelation between IKBIP expression and immune infiltrates in HCC was analyzed through TIMER and tumor-immune system interaction database (TISIDB).Results: Our results revealed that IKBIP expression was abnormally upregulated in HCC, and ROC curve analysis confirmed the diagnostic power of IKBIP. High IKBIP expression was related to tumor sizes, pathologic stage and histologic grade. K-M plotter analysis showed that high IKBIP expression was correlated with poor prognosis of HCC patients. Moreover, multivariate Cox analysis further verified that high IKBIP expression was an independent risk factor in HCC patients. Correlation analysis found that IKBIP expression was associated with infiltrating immune cells.Conclusion: High IKBIP expression is associated with poor prognosis and immune infiltrates, which may serve as a prognostic biomarker and therapeutic target for HCC.


2021 ◽  
Author(s):  
Jianting Du ◽  
Li-rong Xiao ◽  
Guobing Xu ◽  
Bin Zheng ◽  
Chun Chen

Abstract Background: Esophageal cancer (ESCA) is one of the most aggressive and lethal human malignant cancers. It is associated with poor overall survival (OS) and ranks sixth among the causes of cancer-related mortalities. MiR-1301-3p plays vital roles in a majority of malignancies. The aim of this study was to investigate the correlation between miR-1301-3p/NBL1 axis and prognosis of ESCA patients.Methods: We compared the miR-1301-3p expression levels between ESCA and normal esophageal tissues using MiRNAseq data retrieved from The Cancer Genome Atlas (TCGA) database. We employed UALCAN web platform, starBase v3.0 database, R software and GEPIA web platform to perform statistical analysis and data visualization. We then used TargetScan Human, miRDB and DIANA Tools databases to predict the miR-1301-3p target genes. Finally, we analyzed the expression patterns of the target genes as well as their prognostic value in ESCA.Results: There was an overexpression of miR-1301-3p in most malignancies, including ESCA (P<0.001). The miR-1301-3p expression levels were significantly related to age and histologic grade in primary ESCA (P<0.05), with high expression of miR-1301-3p being significantly associated with poor prognosis (Hazard ratio [HR]=1.88, P=0.012). NBL1 was identified as a potential target gene for miR-1301-3p and a negatively correlation in expression levels between the two genes was observed (r=-0.282, P<0.001). Notably, NBL1 was significantly downregulated in ESCA (P<0.001) and its low expression was significantly associated with poor prognosis of ESCA patients (HR=0.53, P=0.0063).Conclusion: miR-1301-3p is a potential biomarker for predicting prognosis of ESCA patients. It may regulate ESCA progression by regulating NBL1 expression.


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098154
Author(s):  
Xin Yuan ◽  
Yize Zhang ◽  
Zujiang Yu

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.


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