scholarly journals Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10470
Author(s):  
Wanzhen Li ◽  
Shiqing Liu ◽  
Shihong Su ◽  
Yang Chen ◽  
Gengyun Sun
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Prognostic Value ◽  
Target Genes ◽  
Predictive Accuracy ◽  
Differentially Expressed ◽  
Prognostic Signature ◽  
Tissue Samples ◽  
Gene Set ◽  
Differentially Expressed Mirnas

MicroRNA (miRNA, miR) has been reported to be highly implicated in a wide range of biological processes in lung cancer (LC), and identification of differentially expressed miRNAs between normal and LC samples has been widely used in the discovery of prognostic factors for overall survival (OS) and response to therapy. The present study was designed to develop and evaluate a miRNA-based signature with prognostic value for the OS of lung adenocarcinoma (LUAD), a common histologic subtype of LC. In brief, the miRNA expression profiles and clinicopathological factors of 499 LUAD patients were collected from The Cancer Genome Atlas (TCGA) database. Kaplan–Meier (K-M) survival analysis showed significant correlations between differentially expressed miRNAs and LUAD survival outcomes. Afterward, 1,000 resample LUAD training matrices based on the training set was applied to identify the potential prognostic miRNAs. The least absolute shrinkage and selection operator (LASSO) cox regression analysis was used to constructed a six-miRNA based prognostic signature for LUAD patients. Samples with different risk scores displayed distinct OS in K-M analysis, indicating considerable predictive accuracy of this signature in both training and validation sets. Furthermore, time-dependent receiver operating characteristic (ROC) analysis demonstrated the nomogram achieved higher predictive accuracy than any other clinical variables after incorporating the clinical information (age, sex, stage, and recurrence). In the stratification analysis, the prognostic value of this classifier in LUAD patients was validated to be independent of other clinicopathological variables, such as age, gender, tumor recurrence, and early stage. Gene set annotation analyses were also conducted through the Hallmark gene set and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, indicating target genes of the six miRNAs were positively related to various molecular pathways of cancer, such as hallmark UV response, Wnt signaling pathway and mTOR signaling pathway. In addition, fresh cancer tissue samples and matched adjacent tissue samples from 12 LUAD patients were collected to verify the expression of miR-582’s target genes in the model, further revealing the potential relationship between SOX9, RASA1, CEP55, MAP4K4 and LUAD tumorigenesis, and validating the predictive value of the model. Taken together, the present study identified a robust signature for the OS prediction of LUAD patients, which could potentially aid in the individualized selection of therapeutic approaches for LUAD patients.

scholarly journals Establishment of a Macrophage Phenotypic Switch Related Prognostic Signature in Patients With Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Mu-xing Li ◽  
Hang-yan Wang ◽  
Chun-hui Yuan ◽  
Zhao-lai Ma ◽  
Bin Jiang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Regression Analysis ◽  
Signaling Pathway ◽  
Risk Score ◽  
Prognostic Value ◽  
Risk Group ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Prognostic Signature ◽  
Phenotypic Switch

IntroductionMacrophage phenotype switch plays a vital role in the progression of malignancies. We aimed to build a prognostic signature by exploring the expression pattern of macrophage phenotypic switch related genes (MRGs) in the Cancer Genome Atlas (TCGA)—pancreatic adenocarcinoma (PAAD), Genotype-Tissue Expression (GTEx)-Pancreas, and Gene Expression Omnibus (GEO) databases.MethodsWe identified the differentially expressed genes between the PAAD and normal tissues. We used single factor Cox proportional risk regression analysis, Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and multivariate Cox proportional hazard regression analysis to establish the prognosis risk score by the MRGs. The relationships between the risk score and immune landscape, “key driver” mutations and clinicopathological factors were also analyzed. Gene-set enrichment analysis (GSEA) analysis was also performed.ResultsWe detected 198 differentially expressed MRGs. The risk score was constructed based on 9 genes (KIF23, BIN1, LAPTM4A, ERAP2, ATP8B2, FAM118A, RGS16, ELMO1, RAPGEFL1). The median overall survival time of patients in the low-risk group was significantly longer than that of patients in the high-risk group (P < 0.001). The prognostic value of the risk score was validated in GSE62452 dataset. The prognostic performance of nomogram based on risk score was superior to that of TNM stage. And GSEA analysis also showed that the risk score was closely related with P53 signaling pathway, pancreatic cancer and T cell receptor signaling pathway. qRT-PCR assay showed that the expressions of the 9 MRGs in PDAC cell lines were higher than those in human pancreatic ductal epithelium cell line.ConclusionsThe nine gene risk score could be used as an independent prognostic index for PAAD patients. Further studies validating the prognostic value of the risk score are warranted.

scholarly journals Bioinformatics Analysis of Differently Expressed Mirnas in CD5 Positive Relapsed and Refractory Diffuse Large B-Cell Lymphoma and Their Potential Theoretical and Clinical Investigations

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 2-3
Author(s):  
Qian Zhang ◽  
Chao Xue ◽  
Xin Wang ◽  
Kang Lu ◽  
Xueling Ge ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
B Cell Lymphoma ◽  
Differentially Expressed ◽  
Ras Signaling ◽  
Differentially Expressed Mirnas ◽  
Ras Signaling Pathway ◽  
Erbb Signaling ◽  
Erbb Signaling Pathway ◽  
Go Terms

Introduction: CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by a poor prognosis, poorly respond to the regulatory treatment strategy, and a relatively high incidence of central nervous system (CNS) infiltration. In this study, we aim to identify key differentially expressed miRNAs (DE-miRNAs) and their target genes in the peripheral blood of CD5+ refractory and relapsed (CD5+ R/R DLBCL) patients. The relationship of the DE-miRNAs and the pathogenesis of CD5+ R/R DLBCL will also be analyzed by bioinformatics tools. Methods: Three female patients with confirmed CD5+ R/R DLBCL were enrolled in this study, their age were 38, 62 and 65 years old, respectively. Three healthy female adults aged 42, 55 and 61, respectively were selected as the control group. The peripheral venous blood of them was collected for RNA extraction and standard small RNA sequencing. Differentially expressed miRNAs analysis was performed with R package edgeR. The target genes of DE-miRNAs were predicted by miRNet. A protein protein interaction (PPI) network was established for these target genes through string database. Functional annotation and pathway enrichment analyses for the target genes were performed through DAVID database to identify their potential functions, target genes, and pathways they might be involved in. Results: 1. Scatter plots, Volcano plots and Heat-maps were used to visualize miRNAs of Differentially expressed genes. As shown in Fig.1, Fig. 2 and Fig. 3. 2. Fifty-five sequences were significantly upregulated and 23 were significantly downregulated in patients with CD5+ R/R DLBCL.Among the candidate miRNAs, 11 up-regulated genes and 4 down-regulated genes were selected according to the log2FC value. The target genes of 11 potential up-regulated and 4 down-regulated DE-miRNAs were successively predicted by As shown in Table 1, a total of 439 and 632 predicted targets of the up-regulated and down-regulated DE-miRNAs were identified, respectively. 3. PPI networks of predicted target genes of 11 upregulated DE-miRNAs (Fig.4a) and 4 downregulated DE-miRNAs (Fig. 4b) were separately constructed using the STRING database and Cytoscape software. According to a degree, the top 10 hub genes in the networks were screened out and were listed inTable 2. Six important hub genes were identified, including two target genes predicted by up-regulating DE-miRNAs, namely NRAS and PIK3R1, and four target genes predicted by down-regulating DE-miRNAs, namely EGFR, VEGFA, IGF1 and Grb2. 4. DAVID now provides a comprehensive set of functional annotation tools for investigators to understand biological meaning. GO analysis was divided into three functional groups, including molecular function (MF), biological processes (BP), and cell composition (CC). The top 10 GO terms of targets of up-regulated DE-miRNAs were presented in Fig.5a-c. The top 10 GO terms of targets of down-regulated DE-miRNAs were shown in Fig. 5d-f. 5. Based on the KEGG database, we analyzed the pathways in which the differentially expressed target genes were involved in. As shown in Fig. 6a-b. The targets of up-regulated DE-miRNAs were enriched in pathways in cancer, oxytocin signaling pathway, ErbB signaling pathway, Rap1 signaling pathway, and proteoglycans in cancer. Whereas the targets of down-regulated DE-miRNAs were enriched in pathways in cancer, Ras signaling pathway, and PI3K-Akt signaling pathway. Conclusions: In this study, we analyzed the differentially expressed miRNAs in CD5+ R/R DLBCL patients, identified their potential functions, target genes, and pathways they might be involved in. This study found that ErbB signaling pathway, Rap1 signaling pathway, Ras signaling pathway and PI3K Akt signaling pathway were the most frequently involved pathways of miRNAs related genes. Target genes including NRAS, PIK3R1, EGFR, VEGFA, IGF1, and Grb2 might have a close relationship in the pathogenesis of CD5+ R/R DLBCL. New targeted drugs related to these pathways and genes may be beneficial to the treatment of CD5+ DLBCL. Our preliminary informatic results might be helpful to deeply understand the pathogenesis and chemotherapy resistance mechanism of CD5+ R/R DLBCL. In the future, we will verify our preliminary informatic results in pathological tissues from patients with CD5+ DLBCL in larger samples. Disclosures No relevant conflicts of interest to declare.

Identification of Three Differentially Expressed miRNAs as Potential Biomarkers for Lung Adenocarcinoma Prognosis

2020 ◽  
Vol 23 (2) ◽  
pp. 148-156
Author(s):  
Wei Wang ◽  
Bin Liu ◽  
Xiaoran Duan ◽  
Xiaolei Feng ◽  
Tuanwei Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Regression Model ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Lasso Regression ◽  
Differentially Expressed Mirnas ◽  
Selection Operator

Objective: The aim of this study areto screen MicroRNAs (miRNAs) related to the prognosis of lung adenocarcinoma (LUAD) and to explore the possible molecular mechanisms. Methods: The data for a total of 535 patients with LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database. The miRNAs for LUAD prognosis were screened by both Cox risk proportional regression model and Last Absolute Shrinkage and Selection Operator (LASSO) regression model. The performances of the models were verified by time-dependent Receiver Operating Characteristic (ROC) curve. The possible biological processes linked to the miRNAs’ target genes were analyzed by Gene Ontology (GO), Kyoto gene and genome encyclopedia (KEGG). Results: Among 127 differentially expressed miRNAs identified from the screening analysis, there are 111 up-regulated and 16 down-regulated miRNAs. Three of them, hsa-miR-1293, hsa-miR-490 and hsa-miR- 5571, were also significantly associated with the survival of the LUAD patients. The targets of the three miRNAs are significantly enriched in systemic lupus erythematosus pathways. Conclusion: Hsa-miR-1293, hsa-miR-490 and hsa-miR-5571 can be potentially used as novel biomarkers for the prognosis prediction of LUAD.

scholarly journals Identification of key miRNA and hub genes in lung adenocarcinoma by bioinformatics and functional analysis

2020 ◽  
Author(s):  
Jiayao Zhu ◽  
Yan Zhang ◽  
Jingjing Lu ◽  
Le Wang ◽  
Xiaoren Zhu ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Lung Adenocarcinoma ◽  
Target Gene ◽  
Target Genes ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Kaplan Meier ◽  
Differentially Expressed Mirnas

Abstract Background: lung adenocarcinoma is the main subtype of lung cancer and the most fatal malignant disease in the world. However, the pathogenesis of lung adenocarcinoma has not been fully elucidated.Methods: Three LUAD-associated datesets (GSE118370, GSE43767 and GSE74190) were downloaded from the Gene Expression Omnibus (GEO) datebase and the differentially expressed miRNAs (DEMs) and genes (DEGs) were screened by GEO2R. The prediction of target gene of differentially expressed miRNA were used miRWALK. Metascape was used to enrich the overlapped genes of DEGs and target genes. Then, the protein-protein interaction(PPI) and DEMs-DEGs regulatory network were created via String datebase and Cytoscape. Finally, overall survival analysis was established via the Kaplan–Meier curve and look for the possible prognostic biomarkers.Result: In this study, 433 differential genes were identified. There were 267 genes overlapped with the target gene of Dems, and eight hub genes (CDH1, CDH5, CAV1, MMP9, PECAM1, CD24, ENG, MME) were screened out. There were 85 different miRNAs in total, among which 16 miRNA target genes intersect with DEGs, 12 miRNAs with the highest interaction were screened out, and survival analysis of miRNA and hub genes was carried out.Conclusion: we found that miRNA-940, miRNA-125a-3p, miRNA-140-3p, miRNA-542-5p, CDH1, CDH5, CAV1, MMP9, PECAM1 may be related to the development of LUAD.

scholarly journals Establishment and validation of a prognostic signature for lung adenocarcinoma based on metabolism‐related genes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhihao Wang ◽  
Kidane Siele Embaye ◽  
Qing Yang ◽  
Lingzhi Qin ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Lung Adenocarcinoma ◽  
Cancer Biology ◽  
Prognostic Value ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Calibration Plot ◽  
Prognostic Signature ◽  
Cox Regression Analysis

Abstract Background Given that dysregulated metabolism has been recently identified as a hallmark of cancer biology, this study aims to establish and validate a prognostic signature of lung adenocarcinoma (LUAD) based on metabolism-related genes (MRGs). Methods The gene sequencing data of LUAD samples with clinical information and the metabolism-related gene set were obtained from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB), respectively. The differentially expressed MRGs were identified by Wilcoxon rank sum test. Then, univariate cox regression analysis was performed to identify MRGs that related to overall survival (OS). A prognostic signature was developed by multivariate Cox regression analysis. Furthermore, the signature was validated in the GSE31210 dataset. In addition, a nomogram that combined the prognostic signature was created for predicting the 1-, 3- and 5-year OS of LUAD. The accuracy of the nomogram prediction was evaluated using a calibration plot. Finally, cox regression analysis was applied to identify the prognostic value and clinical relationship of the signature in LUAD. Results A total of 116 differentially expressed MRGs were detected in the TCGA dataset. We found that 12 MRGs were most significantly associated with OS by using the univariate regression analysis in LUAD. Then, multivariate Cox regression analyses were applied to construct the prognostic signature, which consisted of six MRGs-aldolase A (ALDOA), catalase (CAT), ectonucleoside triphosphate diphosphohydrolase-2 (ENTPD2), glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1), lactate dehydrogenase A (LDHA), and thymidylate synthetase (TYMS). The prognostic value of this signature was further successfully validated in the GSE31210 dataset. Furthermore, the calibration curve of the prognostic nomogram demonstrated good agreement between the predicted and observed survival rates for each of OS. Further analysis indicated that this signature could be an independent prognostic indicator after adjusting to other clinical factors. The high-risk group patients have higher levels of immune checkpoint molecules and are therefore more sensitive to immunotherapy. Finally, we confirmed six MRGs protein and mRNA expression in six lung cancer cell lines and firstly found that ENTPD2 might played an important role on LUAD cells colon formation and migration. Conclusions We established a prognostic signature based on MRGs for LUAD and validated the performance of the model, which may provide a promising tool for the diagnosis, individualized immuno-/chemotherapeutic strategies and prognosis in patients with LUAD.

scholarly journals miR-98-5p as a Novel Biomarker Suppress Liver Fibrosis by Targeting TGFβ Receptor 1

2021 ◽  
Author(s):  
Yanhua Ma ◽  
xiaoxue yuan ◽  
Ming Han ◽  
Kai Han ◽  
Pu Liang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Hbv Infection ◽  
Differentially Expressed ◽  
Control Group ◽  
Chronic Hbv Infection ◽  
Differentially Expressed Mirnas ◽  
Chronic Hbv

Abstract Hepatic fibrosis is the repair reaction of excessive deposition and abnormal distribution of extracellular matrix after various liver injuries, especially chronic HBV infection, which is a key step in the development of various chronic liver diseases to cirrhosis. Recent studies show that microRNAs (miRNA) can regulate a series of liver fibrosis-related gene express and play an important role in the development of liver fibrosis. To detect the miRNAs expression profiling and to screen the differentially expressed miRNAs in patients with HBV-related liver fibrosis, the whole blood was collected from the HBV-related liver fibrosis patients (F2/3, n=10) based on Scheuer’s staging criteria. In addition, healthy volunteers (n=8) served as the control group. The expression of plasma miRNAs was detected by IlluminaHiSeq sequencing. Cluster analysis and target genes prediction of differentially expressed miRNAs were carried out. Gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis of differentially expressed miRNAs target genes were performed. Compared with the healthy control group 104 miRNAs were screened out from the liver fibrosis group, among which 72 miRNAs were up-regulated and 32 were down-regulated. Pathway annotations for the target genes of the miRNAs identified were found that it participated in many signal pathways including MAPK signaling pathway, TNF signaling pathway, Notch signaling pathway, phosphatidylinositol signal system and so on. According to the bioinformatic analysis，miR-98-5p were selected for function research among the differentially expressed miRNAs.MiR-98-5p prevents liver fibrosis by targeting TGFβR1 and blocking TGFβ1/Smad3 signaling pathway. In addition, serum miR-98-5p levels were measured from a total of 70 recruited patients with chronic HBV infection and 29 healthy individuals as controls. We found that serum miR-98-5p level was significantly lower in patients with live fibrosis than in healthy controls and HBV carriers (P<0.05). Those results suggest that miR-98-5p could be a potential therapeutic target for liver fibrosis .

scholarly journals Enrichment and verification of differentially expressed miRNAs in the ovarian tissue of Leizhou black ducks

2021 ◽  
Author(s):  
Lili Lu ◽  
Collins Amponsah Asiamah ◽  
yuanbo Liu ◽  
Rungen Ye ◽  
Yiting Pan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Egg Production ◽  
Target Genes ◽  
Ovarian Tissue ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Signal Pathways ◽  
Laying Performance ◽  
Differentially Expressed Mirnas ◽  
Mirna Library

Abstract Background Ovary is an important reproductive organ for poultry. MicroRNA (miRNA) is a highly conserved class of small non-coding RNA that function in a specific manner to post-transcriptionally regulate gene expression in organisms. Currently, miRNA has been studied extensively but research on duck ovarian tissue is relatively rare. Thus, in this study, we performed the first miRNA analysis of ovarian tissues in Leizhou black ducks with low and high rates of egg production. Method: Using high-throughput sequencing technology, miRNA library was constructed to obtain miRNA expression profile; differentially expressed miRNAs were screened, to predict miRNA target genes. Results A total of 29 differentially expressed miRNAs were obtained from the miRNA library, of which 7 were up-regulated and 22 were down-regulated. Verification of 12 randomly selected miRNAs, using RT-qPCR technology showed the results are consistent with the sequencing data, indicating that the sequencing results are reliable. The GO enrichment and KEGG pathway enrichment analysis of differential miRNAs showed that target genes were significantly enriched in signal pathways related to ovarian development, such as the oxytocin signaling pathway, GnRH signaling pathway, progesterone-mediated oocyte maturation, and AMPK signal pathway. Conclusion The research results enrich the data resources of duck miRNAs, and provide a theoretical basis for further research on the laying performance of poultry and molecular-assisted breeding of poultry in the future.

scholarly journals Establishment and Validation of a Prognostic Signature for Lung Adenocarcinoma Based on Metabolism-Related Genes

2020 ◽  
Author(s):  
Zhihao Wang ◽  
Kidane Siele Embaye ◽  
Qing Yang ◽  
Lingzhi Qin ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Lung Adenocarcinoma ◽  
Cancer Biology ◽  
Prognostic Value ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Calibration Plot ◽  
Prognostic Signature ◽  
Cox Regression Analysis

Abstract Background: Given that dysregulated metabolism has been recently identified as a hallmark of cancer biology, this study aims to establish and validate a prognostic signature of lung adenocarcinoma (LUAD) based on metabolism-related genes(MRGs). Methods: The gene sequencing data of LUAD samples with clinical information and the metabolism-related gene set were obtained from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB), respectively. The differentially expressed MRGs were identified by Wilcoxon rank sum test. Then, univariate Cox regression analysis were performed to identify MRGs that related to overall survival(OS). A prognostic signature was developed by multivariate Cox regression analysis. Furthermore, the signature was validated in the GSE31210 dataset. In addition, a nomogram that combined the prognostic signature was created for predicting the 1-, 3- and 5-year OS of LUAD.The accuracy of the nomogram prediction was evaluated using a calibration plot. Finally, cox regression analysis was applied to identify the prognostic value and clinical relationship of the signature in LUAD. Results: A total of 116 differentially expressed MRGs were detected in the TCGA dataset. We found that 12 MRGs were most significantly associated with OS by using the univariate regression analysis in LUAD. Then, multivariate Cox regression analyses were applied to construct the prognostic signature, which consisted of six MRGs(ALDOA, CAT, ENTPD2, GNPNAT1, LDHA, and TYMS). The prognostic value of this signature was further successfully validated in the GSE31210 dataset. Furthermore, the calibration curve of the prognostic nomogram demonstrated good agreement between the predicted and observed survival rates for each of OS. Further analysis indicated that this signature could be an independent prognostic indicator after adjusting to other clinical factors. Finally, the signature was found to be associated with various clinicopathological features. Conclusions: We established a prognostic signature based on MRGs for LUAD and validated the performance of the model, which may provide a promising tool for the diagnosis and prognosis in patients with LUAD.

scholarly journals miR-98-5p as a Novel Biomarker Suppress Liver Fibrosis by Targeting TGFβ Receptor 1

2021 ◽  
Author(s):  
Yanhua Ma ◽  
xiaoxue yuan ◽  
Ming Han ◽  
Kai Han ◽  
Pu Liang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Hbv Infection ◽  
Differentially Expressed ◽  
Control Group ◽  
Chronic Hbv Infection ◽  
Differentially Expressed Mirnas ◽  
Chronic Hbv

Abstract Hepatic fibrosis is the repair reaction of excessive deposition and abnormal distribution of extracellular matrix after various liver injuries, especially chronic HBV infection, which is a key step in the development of various chronic liver diseases to cirrhosis. Recent studies show that microRNAs (miRNAs) can regulate a series of liver fibrosis-related gene express and play an important role in the development of liver fibrosis. To detect the miRNAs expression profiling and to screen the differentially expressed miRNAs in patients with HBV-related liver fibrosis, the whole blood was collected from the HBV-related liver fibrosis patients (S2/3, n=8) based on Scheuer’s staging criteria. In addition, healthy volunteers(n=7) served as the control group. The expression of plasma miRNAs was detected by IlluminaHiSeq sequencing. Cluster analysis and target genes prediction of differentially expressed miRNAs were performed. Gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis of differentially expressed miRNAs target genes were performed. Compared with the healthy control group 77 miRNAs were screened out from the liver fibrosis group, among which 51 miRNAs were up-regulated and 26 miRNAs were down-regulated. Pathway annotations for the target genes of the miRNAs identified were found that it participated in many signal pathways including MAPK signaling pathway, TNF signaling pathway, Notch signaling pathway, phosphatidylinositol signal system and so on. According to the bioinformatic analysis, miR-98-5p were selected for function research among the differentially expressed miRNAs.MiR-98-5p prevents liver fibrosis by targeting TGFβR1 and blocking TGF β1/Smad3 signaling pathway. In addition, serum miR-98-5p levels were measured from a total of 70 recruited patients with chronic HBV infection and 29 healthy individuals as controls. We found that serum miR-98-5p level was significantly lower in patients with live fibrosis than in healthy controls and HBV carriers (P<0.05). Those results suggest that miR-98-5p could be a potential therapeutic target for liver fibrosis.

scholarly journals Establishment and Validation of a Prognostic Signature for Lung Adenocarcinoma Based on Metabolism-related Genes

2020 ◽  
Author(s):  
Zhihao Wang ◽  
Kidane Siele Embaye ◽  
Qing Yang ◽  
Lingzhi Qin ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Lung Adenocarcinoma ◽  
Cancer Biology ◽  
Prognostic Value ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Calibration Plot ◽  
Prognostic Signature ◽  
Cox Regression Analysis

Abstract Background: Given that dysregulated metabolism has been recently identified as a hallmark of cancer biology, this study aims to establish and validate a prognostic signature of lung adenocarcinoma (LUAD) based on metabolism-related genes(MRGs).Methods: The gene sequencing data of LUAD samples with clinical information and the metabolism-related gene set were obtained from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB), respectively. The differentially expressed MRGs were identified by Wilcoxon rank sum test. Then, univariate Cox regression analysis were performed to identify MRGs that related to overall survival(OS). A prognostic signature was developed by multivariate Cox regression analysis. Furthermore, the signature was validated in the GSE31210 dataset. In addition, a nomogram that combined the prognostic signature was created for predicting the 1-, 3- and 5-year OS of LUAD.The accuracy of the nomogram prediction was evaluated using a calibration plot. Finally, cox regression analysis was applied to identify the prognostic value and clinical relationship of the signature in LUAD.Results: A total of 116 differentially expressed MRGs were detected in the TCGA dataset. We found that 12 MRGs were most significantly associated with OS by using the univariate regression analysis in LUAD. Then, multivariate Cox regression analyses were applied to construct the prognostic signature, which consisted of six MRGs (ALDOA, CAT, ENTPD2, GNPNAT1, LDHA, and TYMS). The prognostic value of this signature was further successfully validated in the GSE31210 dataset. Furthermore, the calibration curve of the prognostic nomogram demonstrated good agreement between the predicted and observed survival rates for each of OS. Further analysis indicated that this signature could be an independent prognostic indicator after adjusting to other clinical factors. The signature was found to be associated with various clinicopathological features. Finally, we confirmed six MRGs protein and mRNA expression in six lung cancer cells and firstly found that ENTPD2 might played an important role on lung adenocarcinoma cell lines clone formation and migration.Conclusions: We established a prognostic signature based on MRGs for LUAD and validated the performance of the model, which may provide a promising tool for the diagnosis and prognosis in patients with LUAD.

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