scholarly journals PGM5: a novel diagnostic and prognostic biomarker for liver cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7070 ◽  
Author(s):  
Yan Jiao ◽  
Yanqing Li ◽  
Peiqiang Jiang ◽  
Wei Han ◽  
Yahui Liu
Keyword(s):  
Liver Cancer ◽  
Prognostic Biomarker ◽  
Area Under The Curve ◽  
Public Health Problem ◽  
Roc Curves ◽  
Normal Liver ◽  
Diagnostic Value ◽  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas ◽  
Metabolic Enzyme

Background Liver cancer is a common malignancy and a significant public health problem worldwide, but diagnosis and prognostic evaluation remain challenging for clinicians. Metabolic reprogramming is a hallmark of cancer, and we therefore examined the diagnostic and prognostic value of a metabolic enzyme, phosphoglucomutase-like protein 5 (PGM5), in liver cancer. Methods All data were from The Cancer Genome Atlas database. R and related statistical packages were used for data analysis. Hepatic PGM5 expression was determined in different groups, and the chi-squared test and Fisher’s exact test were used to determine the significance of differences. The pROC package was used to determine receiver operating characteristic (ROC) curves, the survival package was used to for survival analysis and development of a Cox multivariable model, and the ggplot2 package was used for data visualization. Results PGM5 expression was significantly lower in cancerous than adjacent normal liver tissues, and had modest diagnostic value based on ROC analysis and calculations of area under the curve (AUC). Hepatic PGM5 expression had positive associations with male sex and survival, but negative associations with advanced histologic type, advanced histologic grade, advanced stage, and advanced T classification. Patents with low PGM5 levels had poorer overall survival and relapse-free survival. PGM5 was independently associated with patient prognosis. Conclusion PGM5 has potential use as a diagnostic and prognostic biomarker for liver cancer.

scholarly journals PDK2: a novel diagnostic and prognostic biomarker for liver cancer

2020 ◽  
Author(s):  
Zhi-Cheng Liu ◽  
Yan-Qing Li ◽  
Yan Jiao ◽  
Yue-Chen Zhao
Keyword(s):  
Liver Cancer ◽  
Pyruvate Dehydrogenase ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Normal Liver ◽  
The Cancer Genome Atlas ◽  
High Morbidity ◽  
Cox Regression Analysis ◽  
Diagnosis And Prognosis ◽  
Potential Biomarker

Abstract Background: Liver cancer (LC) is a common malignancy with very high morbidity. Pyruvate dehydrogenase kinases (PDKs) are regulators of mitochondrial pyruvate dehydrogenase complexes (PDCs) and play an important role in regulating cellular energy metabolism. In this study, The Cancer Genome Atlas (TCGA) database was used to analyze the expression of PDK2 mRNA in LC, and to explore the value of PDK2 in the diagnosis and prognosis of LC.Methods: The TCGA database, containing the clinical data of 373 LC patients, includes information on PDK2 expression values. The receiver operating characteristic (ROC) curve of PDK2 was drawn to evaluate its diagnostic ability. Patients were divided into PDK2 high- and low-expressing groups by threshold levels. The Chi-square test was used to evaluate the correlation between PDK2 levels and clinicopathological characteristics. The Kaplan-Meier estimator and Cox regression analysis were performed to assess the effect of PDK2 levels on survival outcomes.Results: PDK2 expression in LC tissue was lower than that in normal liver tissues. According to the area under the curve (AUC) value calculated by ROC, PDK2 has a considerable diagnostic value for LC prognosis. The decreased expression of PDK2 is associated with clinical parameters, such as histologic grade ( P =0.0001), radiation therapy ( P =0.0490), vital status ( P =0.0240), and overall survival (OS) ( P =0.0222). Multivariate analysis shows that decreased PDK2 level is an independent risk factor for predicting poor prognosis in LC.Conclusions: PDK2 has a significant impact on the prognosis of LC and is a potential biomarker for the diagnosis and prognosis of LC.

scholarly journals Modularity of the metabolic gene network as a prognostic biomarker for hepatocellular carcinoma

2017 ◽  
Author(s):  
Fengdan Ye ◽  
Dongya Jia ◽  
Mingyang Lu ◽  
Herbert Levine ◽  
Michael W Deem
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Biomarker ◽  
Malignant Tumors ◽  
Aerobic Glycolysis ◽  
Expression Patterns ◽  
Cancer Recurrence ◽  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas ◽  
Driver Genes ◽  
Tumor Stages

AbstractAbnormal metabolism is an emerging hallmark of cancer. Cancer cells utilize both aerobic glycolysis and oxidative phosphorylation (OXPHOS) for energy production and biomass synthesis. Understanding the metabolic reprogramming in cancer can help design therapies to target metabolism and thereby to improve prognosis. We have previously argued that more malignant tumors are usually characterized by a more modular expression pattern of cancer-associated genes. In this work, we analyzed the expression patterns of metabolism genes in terms of modularity for 371 hepatocellular carcinoma (HCC) samples from the Cancer Genome Atlas (TCGA). We found that higher modularity significantly correlated with glycolytic phenotype, later tumor stages, higher metastatic potential, and cancer recurrence, all of which contributed to poorer prognosis. Among patients with recurred tumor, we found the correlation of higher modularity with worse prognosis during early to mid-progression. Furthermore, we developed metrics to calculate individual modularity, which was shown to be predictive of cancer recurrence and patients’ survival and therefore may serve as a prognostic biomarker. Our overall conclusion is that more aggressive HCC tumors, as judged by decreased host survival probability, had more modular expression patterns of metabolic genes. These results may be used to identify cancer driver genes and for drug design.

scholarly journals An angiogenesis-related long noncoding RNA signature correlates with prognosis in patients with hepatocellular carcinoma

2021 ◽  
Vol 41 (4) ◽  
Author(s):  
Dengliang Lei ◽  
Yue Chen ◽  
Yang Zhou ◽  
Gangli Hu ◽  
Fang Luo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Enrichment Analysis ◽  
Clinical Information ◽  
Roc Curves ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Highly Correlated

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide. Neovascularization is closely related to the malignancy of tumors. We constructed a signature of angiogenesis-related long noncoding RNA (lncRNA) to predict the prognosis of patients with HCC. The lncRNA expression matrix of 424 HCC patients was downloaded from The Cancer Genome Atlas (TCGA). First, gene set enrichment analysis (GSEA) was used to distinguish the differentially expressed genes of the angiogenesis genes in liver cancer and adjacent tissues. Next, a signature of angiogenesis-related lncRNAs was constructed using univariate and multivariate analyses, and receiver operating characteristic (ROC) curves were used to assess the accuracy. The signature and relevant clinical information were used to construct the nomogram. A 5-lncRNA signature was highly correlated with overall survival (OS) in HCC patients and performed well in evaluations using the C-index, areas under the curve, and calibration curves. In summary, the 5-lncRNA model can serve as an accurate signature to predict the prognosis of patients with liver cancer, but its mechanism of action must be further elucidated by experiments.

scholarly journals Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Lu Zhang ◽  
Huihui Li ◽  
Ming Yuan ◽  
Dong Li ◽  
Chang Sun ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Pcr Analysis ◽  
Go Annotation ◽  
Qrt Pcr ◽  
Noninvasive Biomarker ◽  
Novel Biomarkers ◽  
Negative Controls ◽  
Exosomal Mirna

Background. A reliable noninvasive biomarker is not yet available for endometriosis diagnosis. Novel biomarkers for the diagnosis of endometriosis are urgently needed. The molecular constituents of exosomes, especially exosomal microRNAs (miRNAs), have considerable potential as novel biomarkers for clinical diagnosis. This study is aimed at exploring aberrant exosomal miRNA profiles by using miRNA microarray and at providing more accurate molecular biomarkers of endometriosis. Methods. Exosomes were isolated from the serum of patients with endometriosis and negative controls and identified by electron microscopy, nanoparticle tracking analysis, and Western blot. Exosomal miRNAs were profiled by miRNA microarrays. The expression of selective serum exosomal miRNA was validated by qRT-PCR. Receiver operating characteristic (ROC) curves were established to explore the diagnostic value of selective miRNAs. Finally, GO annotation and KEGG pathway enrichment analyses were used to display possible functions associated with the two miRNAs. Results. A total of 24 miRNAs showed differential levels of enrichment with P<0.05 and log2 fold change>1 by miRNA microarrays. Among the six selective miRNAs (i.e., miR-134-5p, miR-197-5p, miR-22-3p, miR-320a, miR-494-3p, and miR-939-5p), qRT-PCR analysis revealed that miR-22-3p and miR-320a were significantly upregulated in serum exosomes from patients with endometriosis compared with negative individuals. ROC curve revealed that the serum exosomal miR-22-3p and miR-320a yielded the area under the curve values of 0.855 and 0.827, respectively. Conclusion. Our results demonstrated that exosomal miR-22-3p and miR-320a were significantly increased in the sera of patients with endometriosis. The two miRNAs may be useful potential biomarkers for endometriosis diagnosis.

scholarly journals Prognostic Signatures of Alternative Splicing Events in Esophageal Carcinoma Based on TCGA Splice-Seq Data

2021 ◽  
Vol 11 ◽  
Author(s):  
Ping Ye ◽  
Yan Yang ◽  
Liqiang Zhang ◽  
Guixi Zheng
Keyword(s):  
Alternative Splicing ◽  
Esophageal Carcinoma ◽  
Cox Regression ◽  
Donor Site ◽  
Area Under The Curve ◽  
Clinical Information ◽  
Roc Curves ◽  
The Cancer Genome Atlas ◽  
Acceptor Site ◽  
Cox Regression Analysis

An alternative splicing (AS) event is a highly complex process that plays an essential role in post-transcriptional gene expression. Several studies have suggested that abnormal AS events were the primary element in the pathological process of cancer. However, few works are dedicated to the study of AS events in esophageal carcinoma (EC). In the present study, clinical information and RNA-seq data of EC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The percent spliced in (PSI) values of AS events were acquired from the TCGA Splice-seq. A total of 183 EC patients were enrolled in this study, and 2,212 AS events were found significantly associated with the overall survival of these patients by univariate Cox regression analysis. The prognostic signatures based on AS events were built by multivariate Cox analysis. Receiver operating characteristic (ROC) curves displayed that the area under the curve (AUC) of the following prognostic signatures, including exon skip (ES), alternate terminator (AT), alternate acceptor site (AA), alternate promoter (AP), alternate donor site (AD), retained intron (RI), and total events, was greater than 0.8, suggesting that these seven signatures had valuable prognosis prediction capacity. Finally, the risk score of prognostic signatures was indicated as an independent risk factor of survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the function of splicing factors (SFs) that were associated with AS events. Also, the interactive network between AS events and SFs identified several hub genes and AS events which need further study. This was a comprehensive study that explored prognosis-related AS events and established valuable prognosis signatures in EC patients. The network of interactions between AS events and SFs might offer novel insights into the fundamental mechanisms of tumorigenesis and progression of EC.

scholarly journals Identification of F5 as a Prognostic Biomarker in Patients with Gastric Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Yi Liu ◽  
Xi-Wen Liao ◽  
Yu-Zhou Qin ◽  
Xian-Wei Mo ◽  
Shan-Shan Luo
Keyword(s):  
Gastric Cancer ◽  
Survival Analysis ◽  
Prognostic Biomarker ◽  
Area Under The Curve ◽  
Coagulation Factor ◽  
The Cancer Genome Atlas ◽  
Factor V ◽  
Kaplan Meier ◽  
Km Plotter ◽  
Gastric Cancer Patients

Association of Coagulation factor V (F5) polymorphisms with the occurrence of many types of cancers has been widely reported, but whether it is of prognostic relevance in some cancers remain to be resolved. The RNA-sequencing dataset was downloaded from The Cancer Genome Atlas (TCGA). The potential of F5 genes to predict the survival time of gastric cancer (GC) patients was investigated using univariate and multivariate survival analysis whereas “Kaplan-Meier plotter” (KM-plotter) online tools were employed to validate the outcomes. TCGA data revealed that F5 mRNA levels were significantly upregulated in gastric cancer samples. Survival analysis confirmed that high levels of F5 mRNA correlated with short overall survival (OS) in gastric cancer patients, and the area under the curve (AUC) values of 1-, 2-, and 5-year OS rate were 0.554, 0.593, and 0.603, respectively. Survival analysis by KM-plotter indicated that the high expression of F5 mRNA was significantly associated with a shorter OS compared with the low expression level in all patients with GC, and this was also the case for patients in stage III (hazard ratio HR=1.78, P=0.017). These findings suggest that the F5 gene is significantly upregulated in GC tumour tissues, and may be a potential prognostic biomarker for GC.

scholarly journals Inflammatory Breast Carcinoma: Elevated microRNA miR-181b-5p and Reduced miR-200b-3p, miR-200c-3p, and miR-203a-3p Expression as Potential Biomarkers with Diagnostic Value

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1059
Author(s):  
Sarah Atef Fahim ◽  
Mahmoud Salah Abdullah ◽  
Nancy A. Espinoza-Sánchez ◽  
Hebatallah Hassan ◽  
Ayman M. Ibrahim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Diagnostic Accuracy ◽  
Operating Characteristic ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Differentially Expressed Mirnas ◽  
E Box ◽  
Aggressive Breast Cancer ◽  
Potential Biomarkers

Inflammatory breast cancer (IBC) is a rare yet aggressive breast cancer variant, associated with a poor prognosis. The major challenge for IBC is misdiagnosis due to the lack of molecular biomarkers. We profiled dysregulated expression of microRNAs (miRNAs) in primary samples of IBC and non-IBC tumors using human breast cancer miRNA PCR array. We discovered that 28 miRNAs were dysregulated (10 were upregulated, while 18 were underexpressed) in IBC vs. non-IBC tumors. We identified 128 hub genes, which are putative targets of the differentially expressed miRNAs and modulate important cancer biological processes. Furthermore, our qPCR analysis independently verified a significantly upregulated expression of miR-181b-5p, whereas a significant downregulation of miR-200b-3p, miR-200c-3p, and miR-203a-3p was detected in IBC tumors. Receiver operating characteristic (ROC) curves implied that the four miRNAs individually had a diagnostic accuracy in discriminating patients with IBC from non-IBC and that miR-203a-3p had the highest diagnostic value with an AUC of 0.821. Interestingly, a combination of miR-181b-5p, miR-200b-3p, and miR-200c-3p robustly improved the diagnostic accuracy, with an area under the curve (AUC) of 0.897. Intriguingly, qPCR revealed that the expression of zinc finger E box-binding homeobox 2 (ZEB2) mRNA, the putative target of miR-200b-3p, miR-200c-3p, and miR-203a-3p, was upregulated in IBC tumors. Overall, this study identified a set of miRNAs serving as potential biomarkers with diagnostic relevance for IBC.

Provocation testing is irreplaceable to uncover or refute Brugada syndrome – an electrocardiographic validation study during ajmaline provocation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.H Van Der Ree ◽  
J Vendrik ◽  
J.A Kors ◽  
A.A.M Wilde ◽  
H.L Tan ◽  
...  
Keyword(s):  
Brugada Syndrome ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Peak Effect ◽  
Characteristic Type ◽  
Predictive Values ◽  
Provocation Tests ◽  
Diagnostic Characteristics

Abstract Background A Brugada syndrome (BrS) diagnosis is made upon documenting its characteristic type-1 ECG abnormality, being either spontaneously present or provoked by drug challenge, in the absence of co-morbidities resulting in similar ECG characteristics. In patients without type-1 ECG but in whom a suspicion of BrS exists, several ECG characteristics have been proposed that could aid in distinguishing BrS from non-BrS, particularly in individuals with incomplete right bundle branch block. Purpose To validate the diagnostic value of ECG characteristics that were previously proposed. Methods For this retrospective study, ECGs were evaluated from consecutive patients suspected of BrS who underwent ajmaline testing (n=1392). Baseline ECG and peak-effect ECG were analyzed with the MEANS software. Parameters considered were P, PR, QRS, S, JT, QT and QTc durations (all in ms), J and S amplitudes (both in mV), and QRS and T axes (both in °). ECG evaluations also included b-angles (in °) and duration of the base of a triangle (DBT) at 0.5 mV from the r' (in ms) in right precordial leads (V1, V2, V1ic3, V2ic3). Results Diagnostic type-1 ECGs were uncovered in 345 subjects and 1047 subjects had a negative test. Patients with BrS had significantly more atrial and ventricular conduction abnormalities (P, PR, QRS, and S duration) at baseline; these differences, except in PR duration, were aggravated upon ajmaline administration. In particular, the b-angle (e.g., V1: 28° [20; 46.5] versus 18° [12; 24], p&lt;0.01) and DBT (e.g., V1: 130 ms [89; 214] versus 65 ms [42; 92.3], p&lt;0.01) were significantly larger at baseline in patients with BrS, however, only with modest diagnostic value (area-under-the-curve 0.67–0.80). The optimal b-angle cut-off value based on the ROC curves to rule out BrS was determined at an angle of &gt;15°, negative predictive values ranged from 78.6–95.5 and sensitivities ranged from 80–98.1% among different leads. Conclusions Patients with BrS show more baseline ECG abnormalities and display more conduction slowing upon ajmaline infusion. The b-angle and DBT do not demonstrate strong enough diagnostic characteristics to serve as a stand-alone diagnostic tool. Drug provocation tests remain necessary for diagnosing BrS in patients without a spontaneous type-1 ECG. Funding Acknowledgement Type of funding source: None

scholarly journals Prognostic significance and oncogene function of cathepsin A in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huaxiang Wang ◽  
Fengfeng Xu ◽  
Fang Yang ◽  
Lizhi Lv ◽  
Yi Jiang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Oxidative Phosphorylation ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Normal Liver ◽  
Diagnostic Value ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Clinical Value ◽  
Lysosomal Protease

AbstractCathepsin A (CTSA) is a lysosomal protease that regulates galactoside metabolism. The previous study has shown CTSA is abnormally expressed in various types of cancer. However, rarely the previous study has addressed the role of CTSA in hepatocellular carcinoma (HCC) and its prognostic value. To study the clinical value and potential function of CTSA in HCC, datasets from the Cancer Genome Atlas (TCGA) database and a 136 HCC patient cohort were analyzed. CTSA expression was found to be significantly higher in HCC patients compared with normal liver tissues, which was supported by immunohistochemistry (IHC) validation. Both gene ontology (GO) and The Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that CTSA co-expressed genes were involved in ATP hydrolysis coupled proton transport, carbohydrate metabolic process, lysosome organization, oxidative phosphorylation, other glycan degradation, etc. Survival analysis showed a significant reduction both in overall survival (OS) and recurrence-free survival (RFS) of patients with high CTSA expression from both the TCGA HCC cohort and 136 patients with the HCC cohort. Furthermore, CTSA overexpression has diagnostic value in distinguishing between HCC and normal liver tissue [Area under curve (AUC) = 0.864]. Moreover, Gene set enrichment analysis (GSEA) showed that CTSA expression correlated with the oxidative phosphorylation, proteasome, and lysosome, etc. in HCC tissues. These findings demonstrate that CTSA may as a potential diagnostic and prognostic biomarker in HCC.

scholarly journals Diagnostic Value of the Methylation of Multiple Gene Promoters in Serum in Hepatitis B Virus-Related Hepatocellular Carcinoma

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Xueyan Dong ◽  
Qiang Hou ◽  
Yueming Chen ◽  
Xianjun Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Gene Promoters ◽  
Multiple Gene ◽  
B Virus ◽  
Better Than

This study sought to evaluate the diagnostic value of the methylation of multiple gene promoters in serum in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). A total of 343 participants were enrolled, including 98 patients with HCC, 75 patients with liver cirrhosis (LC), 90 patients with chronic hepatitis B (CHB), and 80 healthy individuals. RASSF1A, APC, BVES, TIMP3, GSTP1, and HOXA9 were selected as the candidate genes. The MethyLight method was used to assay promoter methylation statuses. The diagnostic performances of markers were assessed by constructing receiver operating characteristic (ROC) curves. The prevalences of methylation for RASSF1A, APC, BVES, HOXA9, GSTP1, and TIMP3 were 52.04%, 36.73%, 29.59%, 20.41%, 17.35%, and 11.22%, respectively. APC methylation completely overlapped with RASSF1A methylation. The area under the curve (AUC) for RASSF1A methylation (0.718) was better than the corresponding AUC for AFP (0.609) in distinguishing HCC from CHB. When RASSF1A, BVES, HOXA9, and AFP were combined, the AUC was 0.852 (95% CI = 0.796–0.908, P=0.028), and the sensitivity and specificity were 83.7% and 78.9%, respectively. In conclusion, an assay that combines methylation of the RASSF1A, BVES, and HOXA9 gene promoters in serum and AFP could significantly improve HBV-related HCC diagnoses.

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