Identification of associated molecular events in Helicobacter pylori infection and gastric cancer through integrated computational analysis of Microarray and RNA-Seq datasets

Abstract According to the World Health Organization, Gastric cancer (GC) is the third leading cause of death worldwide, where, the major precursor of cancer progression is infection with Helicobacter pylori. It has been reported that 50% of the total populace is infected with H.pylori, while in 80% the ulcer emerges in later stages of the infection. Although extensive separate analysis has been performed on H.pylori infection and GC data, however, there is a need to perform comparative analysis to identify the cross-talk between the conditions and to hunt significant molecular events that occurs during H.pylori induced GC. The aim of this multi-population study was to identify common molecular events and potential bio-markers against H.pylori induced GC. We performed microarray and RNA-seq analysis on publicly available H.pylori infection, gastritis, H.pylori induced GC and GC datasets to obtain Differentially Expressed Genes (DEGs). After obtaining the DEGs, integrative analysis, functional enrichment analysis and network biology approaches were utilized to identify common markers and hub genes between various disease conditions. Functional enrichment analysis revealed the DEGs of H.pylori infection, gastritis, H.pylori induced GC and GC were strongly associated with spliceosome, adherens junction, focal adhesion and ribosome. Being one of the common DEG, and highly interactive hub protein in the networks of all the conditions, translationally controlled tumour protein (TPT1) was identified as a significant predictive biomarker for early prognosis and diagnosis of H.pylori induced GC. Therefore, the mechanisms behind TPT1 should be further studied using in vitro cell-based functional assays, to determine its role in the progression of H.pylori induced GC.

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Long Noncoding RNA RP11-357H14.17 Plays an Oncogene Role in Gastric Cancer by Activating ATF2 Signaling and Enhancing Treg Cells

BioMed Research International ◽

10.1155/2021/6635936 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Tang Xiaoli ◽

Wang Wenting ◽

Zhang Meixiang ◽

Zuo Chunlei ◽

Hu Chengxia

Keyword(s):

Gastric Cancer ◽

Noncoding Rna ◽

Prognostic Value ◽

Malignant Tumors ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Treg Cells ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Biological Behavior

Background. Gastric cancer (GC) is one of the most common malignant tumors in the world. The potential functions and mechanisms of long noncoding RNAs (lncRNAs) in GC development are still unclear. It is of great significance to explore the prognostic value of LncRNA signatures for GC. Methods. LncRNAs differently expressed in GC and their prognostic value were studied based on The Cancer Genome Atlas (TCGA) database. The functional regulatory network and immune infiltration of RP11-357H14.17 were further studied using a variety of bioinformatics tools and databases. Results. We found that the high expression of RP11-357H14.17 was closely associated with shortened overall survival (OS) and poor prognosis in gastric cancer patients. We also found that its expression was related to clinical features including tumor volume, metastasis, and differentiation. Functional enrichment analysis revealed that RP11-357H14.17 is closely related to enhanced DNA replication and metabolism; ssGSEA analysis implied the oncogenic roles of RP11-357H14.17 was related to ATF2 signaling and Treg cell differentiation. Furthermore, we verified such link by using real-time PCR and IHC staining in human GC samples. Conclusion. We demonstrate that RP11-357H14.17 may play a crucial role in the occurrence, development, and malignant biological behavior of gastric cancer as a potential prognostic marker for gastric cancer.

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Identification of novel potential biomarkers in hepatocarcinoma cancer; a transcriptome analysis

10.21203/rs.3.rs-154350/v3 ◽

2021 ◽

Author(s):

Mohib kakar ◽

Muhammad Mehboob ◽

Muhammad Akram ◽

Imran Iqbal ◽

Hafza Ijaz ◽

...

Keyword(s):

Gene Expression ◽

Cancer Progression ◽

Predictive Biomarkers ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Gene Expression Omnibus ◽

Functional Enrichment ◽

Molecular Therapy ◽

Hub Genes ◽

Healthy Control

Abstract Objective The goal of this study was to understand possible core genes associated with hepatocellular carcinoma (HCC) pathogenesis and prognosis. Methods GEO contains datasets of gene expression, miRNA and methylation patterns of diseased and healthy/control patients. GSE62232 Dataset was selected by employing the server Gene Expression Omnibus. A total of 91 samples were collected, including 81 HCC samples and 10 healthy samples as control. GSE62232 was analyzed through GEO2R, and Functional Enrichment Analysis was performed to extract rational information from a set of DEGs. The Protein-Protein Relationship Networking search method has been used for extracting genes interacting. MCC method was used to calculate the top 10 genes according to their importance. Hub genes in the network were analyzed using GEPIA to estimate the effect of their differential expression on cancer progression. Results We identified the top 10 hub genes through Cytohubba plugin. These genes include Cell Cycle Regulatory Cyclins and Cyclin-dependent proteins CCNA2, CCNB1 and CDK1. The pathogenesis and prognosis of HCC may be directly linked with the aforementioned genes. Conclusion In this analysis, we found critical genes for HCC that showed recommendations for more diagnostic and predictive biomarkers studies that could promote selective molecular therapy for HCC.

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Molecular characterization of metabolic subtypes of gastric cancer based on metabolism-related lncRNA

Scientific Reports ◽

10.1038/s41598-021-00410-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lingdi Li ◽

Jianfei Ma

Keyword(s):

Gastric Cancer ◽

Metabolic Pathways ◽

Metabolic Regulation ◽

Protective Factor ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Underlying Mechanism ◽

Functional Enrichment ◽

Biological Processes

AbstractIncreasing evidence has demonstrated that lncRNAs are critical regulators in diverse biological processes, but the function of lncRNA in metabolic regulation remains largely unexplored. In this study, we evaluated the association between lncRNA and metabolic pathways and identified metabolism-related lncRNAs. Gastric cancer can be mainly subdivided into 2 clusters based on these metabolism-related lncRNA regulators. Comparative analysis shows that these subtypes are found to be highly consistent with previously identified subtypes based on other omics data. Functional enrichment analysis shows that they are enriched in distinct biological processes. Mutation analysis shows that ABCA13 is a protective factor in subtype C1 but a risk factor in C2. Analysis of chemotherapeutic and immunotherapeutic sensitivity shows that these subtypes tend to display distinct sensitivity to the same chemical drugs. In conclusion, these findings demonstrated the significance of lncRNA in metabolic regulation. These metabolism-related lncRNA regulators can improve our understanding of the underlying mechanism of lncRNAs and advance the research of immunotherapies in the clinical management of gastric cancer.

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Identification of Novel Potential Biomarkers in Hepatocarcinoma Cancer; A Transcriptome Analysis

10.21203/rs.3.rs-154350/v1 ◽

2021 ◽

Author(s):

Mohib kakar ◽

Muhammad Mehboob ◽

Muhammad Akram ◽

Imran Iqbal ◽

Hafza Ijaz ◽

...

Keyword(s):

Gene Expression ◽

Cancer Progression ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Predictive Biomarker ◽

Gene Expression Omnibus ◽

Functional Enrichment ◽

Molecular Therapy ◽

Hub Genes ◽

Healthy Control

Abstract The goal of this study was to understand possible core genes associated with hepatocellular carcinoma (HCC) pathogenesis and prognosis. Gene Expression Omnibus (GEO) contains datasets of gene expression, miRNA and methylation patterns of diseased and healthy/control patients. GSE62232 Dataset was selected by employing the server GEO. A total of 91 samples were collected, including 81 HCC samples and 10 healthy samples as control. GSE62232 was analyzed through GEO2R, and functional enrichment analysis was performed to extract rational information from a set of DEGs. The protein-protein relationship networking search method was used for extracting interacting genes. MCC method was used to calculate the top 10 genes according to their importance. Hub genes in the network were analyzed using GEPIA to estimate the effect of their differential expression on cancer progression. We identified the top 10 hub genes through Cytohubba plugin. These genes include cell cycle regulatory cyclins and cyclin-dependent proteins CCNA2, CCNB1 and CDK1. The pathogenesis and prognosis of HCC may be directly linked with the aforementioned genes. In this analysis, we found critical genes for HCC that showed recommendations for more diagnostic and predictive biomarker studies that could promote selective molecular therapy for HCC.

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Detecting Hub Genes Associated With Lauren Subtype of Gastric Cancer by Weighted Gene Co-Expression Network Analysis

10.21203/rs.3.rs-61626/v1 ◽

2020 ◽

Author(s):

XU LIU ◽

Li Yao ◽

Jingkun Qu ◽

Lin Liu ◽

XU LIU ◽

...

Keyword(s):

Gastric Cancer ◽

Network Analysis ◽

Cancer Survival ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Diffuse Gastric Cancer ◽

Hub Genes ◽

Gene Modules

Abstract Background Gastric cancer is a rather heterogeneous type of malignant tumor. Among the several classification system, Lauren classification can reflect biological and pathological differences of different gastric cancer.Method to provide systematic biological perspectives, we employ weighted gene co-expression network analysis to reveal transcriptomic characteristics of gastric cancer. GSE15459 and TCGA STAD dataset were downloaded. Co-expressional network was constructed and gene modules were identified. Result Two key modules blue and red were suggested to be associated with diffuse gastric cancer. Functional enrichment analysis of genes from the two modules was performed. Validating in TCGA STAD dataset, we propose 10 genes TNS1, PGM5, CPXM2, LIMS2, AOC3, CRYAB, ANGPTL1, BOC and TOP2A to be hub-genes for diffuse gastric cancer. Finally these ten genes were associated with gastric cancer survival. Conclusion More attention need to be paid and further experimental study is required to elucidate the role of these genes.

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A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma

BioMed Research International ◽

10.1155/2020/5973082 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

KunZhe Wu ◽

ChunDong Zhang ◽

Cheng Zhang ◽

DongQiu Dai

Keyword(s):

Growth Factor ◽

Esophageal Carcinoma ◽

Target Genes ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Rna Seq ◽

Mirna Signature ◽

Cox Regression Analysis ◽

Ppi Networks

Objective. We identified differentially expressed microRNAs (DEMs) between esophageal carcinoma (ESCA) tissues and normal esophageal tissues. We then constructed a novel three-miRNA signature to predict the prognosis of ESCA patients using bioinformatics analysis. Materials and Methods. We combined two microarray profiling datasets from the Gene Expression Omnibus (GEO) database and RNA-seq datasets from the Cancer Genome Atlas (TCGA) database to analyze DEMs in ESCA. The clinical data from 168 ESCA patients were selected from the TCGA database to assess the prognostic role of the DEMs. The TargetScan, miRDB, miRWalk, and DIANA websites were used to predict the miRNA target genes. Functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (David), and protein-protein interaction (PPI) networks were obtained using the Search Tool for the Retrieval of Interacting Genes database (STRING). Results. With cut-off criteria of P<0.05 and |log2FC| > 1.0, 33 overlapping DEMs, including 27 upregulated and 6 downregulated miRNAs, were identified from GEO microarray datasets and TCGA RNA-seq count datasets. The Kaplan–Meier survival analysis indicated that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) was significantly associated with the overall survival of ESCA patients. The results of univariate and multivariate Cox regression analysis showed that the three-miRNA signature was a potential prognostic factor in ESCA. Furthermore, the gene functional enrichment analysis revealed that the target genes of the three miRNAs participate in various cancer-related pathways, including viral carcinogenesis, forkhead box O (FoxO), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (ErbB2), and mammalian target of rapamycin (mTOR) signaling pathways. In the PPI network, three target genes (MAPK1, RB1, and CLTC) with a high degree of connectivity were selected as hub genes. Conclusions. Our results revealed that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) is a potential novel prognostic biomarker for ESCA.

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Genome-wide phylogenetic analysis, expression pattern, and transcriptional regulatory network of the pig C/EBP gene family

10.21203/rs.3.rs-96827/v1 ◽

2020 ◽

Author(s):

Chaoxin Zhang ◽

Tao Wang ◽

Shengwei Liu ◽

Bing Zhang ◽

Xue Li ◽

...

Keyword(s):

Phylogenetic Analysis ◽

Regulatory Network ◽

Target Genes ◽

Transcriptional Regulatory Network ◽

Expression Patterns ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Rna Seq ◽

Group I

Abstract Background: The vertebrate C/EBP transcription factors regulate many important biological processes, such as cell proliferation, differentiation, signal transduction, inflammation, and energy metabolism. The first C/EBP protein was identified in rat liver nuclei. Development of sequencing technology resulted in identification of the C/EBP genes in various species. In this study, a bioinformatics approach was used to determine the distribution of the members of the C/EBP family in vertebrates. A phylogenetic tree was constructed to analyze the C/EBP genes in vertebrates. Based on RNA-seq data, the expression patterns of pig C/EBP members in various tissues were analyzed. In addition, a gene transcription regulatory network was constructed with pig C/EBP members as the core.Results: We identified a total of 92 C/EBP genes in 17 vertebrate genomes. Phylogenetic analysis showed that all C/EBP TFs were classified into two groups; group I contained C/EBPβ TFs, and group II contained the remaining C/EBP TFs. The C/EBPα, C/EBPβ, C/EBPδ, C/EBPγ, and C/EBPζ genes were expressed ubiquitously with inconsistent expression patterns in various tissues. Moreover, a pig C/EBP regulatory network was constructed, including C/EBP genes, TFs, and miRNAs. A total of 39 FFL motifs were detected in the pig C/EBP regulatory network. Based on the RNA-seq data, gene expression patterns related to this FFL sub-network were analyzed in 27 adult Duroc tissues. Certain FFL motifs may be tissue specific. Functional enrichment analysis indicated that C/EBP and its target genes are involved in many important biological pathways. Conclusions: These results provide valuable information that clarifies the evolutionary relationships of the C/EBP family and contributes to the understanding of the biological function of C/EBP genes.

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Downregulated miR-383-5p contributes to the proliferation and migration of gastric cancer cells and is associated with poor prognosis

PeerJ ◽

10.7717/peerj.7882 ◽

2019 ◽

Vol 7 ◽

pp. e7882 ◽

Cited By ~ 9

Author(s):

Chao Wei ◽

Jian-Jun Gao

Keyword(s):

Gastric Cancer ◽

Target Genes ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Luciferase Reporter ◽

Reporter Assay ◽

Qrt Pcr ◽

And Migration ◽

Proliferation And Migration

Aim The study aims to identify differentially expressed microRNAs (DEMs) in gastric cancer (GC) and explore the expression, prognosis and downstream regulation role of miR-383-5p in GC. Methods The GC miRNA-Seq and clinical information were downloaded from Firebrowse which stores integrated data sourced from The Cancer Genome Atlas database. The DEMs were identified with limma package in R software at the cut-off criteria of P < 0.05 and |log2 fold change| > 1.0 (|log2FC| > 1.0). The expression of miR-383-5p in GC cell lines and 54 paired GC tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The overall survival curve of miR-383-5p and the association between its expression and clinicopathological features were explored. Wound healing and cell counting kit-8 assays were performed to investigate the capacity of miR-383-5p in cell proliferation and migration. The downstream target genes were predicted by bioinformatics tools (miRDB, TargetScan and starBase). The consensus target genes were selected for gene functional enrichment analysis by FunRich v3.0 software. The luciferase reporter assay was performed to verify the potential targeting sites of miR-383-5p on lactate dehydrogenase A (LDHA). Results A total of 21 down-regulated miRNAs (including miR-383-5p) and 202 up-regulated miRNAs were identified by analyzing GC miRNA-Seq data. Survival analysis found that patients with low miR-383-5p expression had a shorter survival time (median survival time 21.1 months) than those with high expression (46.9 months). The results of qRT-PCR indicated that miR-383-5p was downregulated in GC cell lines and tissues, which was consistent with miRNA-Seq data. The expression of miR-383-5p was significantly associated with tumor size and differentiation grade. Besides, overexpression of miR-383-5p suppressed GC cells proliferation and migration. A total of 49 common target genes of miR-383-5p were obtained by bioinformatics tools and gene functional enrichment analysis showed that these predicted genes participated in PI3K, mTOR, c-MYC, TGF-beta receptor, VEGF/VEGFR and E-cadherin signaling pathways. The data showed that expression of miR-383-5p was negatively correlated with target LDHA (r = −0.203). Luciferase reporter assay suggested that LDHA was a target of miR-383-5p. Conclusion The present study concluded that miR-383-5p was downregulated and may act as a tumor suppressor in GC. Furthermore, its target genes were involved in important signaling pathways. It could be a prognostic biomarker and play a vital role in exploring the molecular mechanism of GC.

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Integrated Analysis of lncRNA and mRNA Reveals Novel Insights into Wool Bending in Zhongwei Goat

Animals ◽

10.3390/ani11113326 ◽

2021 ◽

Vol 11 (11) ◽

pp. 3326

Author(s):

Xiaobo Li ◽

Zhanfa Liu ◽

Shaohui Ye ◽

Yue Liu ◽

Qian Chen ◽

...

Keyword(s):

Signaling Pathway ◽

Target Genes ◽

Economic Value ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Hair Follicles ◽

Functional Enrichment ◽

Integrated Analysis ◽

Rna Seq ◽

Camp Signaling Pathway

Chinese Zhongwei goat is a rare and precious fur breed as its lamb fur is a well-known fur product. Wool bending of lamb fur of the Zhongwei goat is its most striking feature. However, the curvature of the wool decreases gradually with growth, which significantly affects its quality and economic value. The mechanism regulating the phenotypic changes of hair bending is still unclear. In the present study, the skin tissues of Zhongwei goats at 45 days (curving wool) and 108 days (slight-curving wool) after birth were taken as the research objects, and the expression profiling of long non-coding RNAs (lncRNAs) and mRNAs were analyzed based on the Ribo Zero RNA sequencing (RNA-seq) method. In total, 46,013 mRNAs and 13,549 lncRNAs were identified, of which 352 were differentially expressed mRNAs and 60 were. lncRNAs. Functional enrichment analysis of the target genes of lncRNAs were mainly enriched in PI3K-Akt, Arachidonic acid metabolic, cAMP, Wnt, and other signaling pathways. The qRT-PCR results of eight selected lncRNAs and target genes were consistent with the sequencing result, which indicated our data were reliable. Through the analysis of the weighted gene co-expression network, 13 co-expression modules were identified. The turquoise module contained a large number of differential expressed lncRNAs, which were mainly enriched in the PI3K-Akt signaling pathway and cAMP signaling pathway. The predicted LOC102172600 and LOC102191729 might affect the development of hair follicles and the curvature of wool by regulating the target genes. Our study provides novel insights into the potential roles of lncRNAs in the regulation of wool bending. In addition, the study offers a theoretical basis for further study of goat wool growth, so as to be a guidance and reference for breeding and improvement in the future.

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Clinical significance and potential mechanisms of the RNA methyltransferase KIAA1429 in osteosarcoma

10.21203/rs.3.rs-227839/v1 ◽

2021 ◽

Author(s):

Yu Sun ◽

Yi-wu Lei ◽

Shu-Fan Ji ◽

Hao Wu ◽

Yun Liu ◽

...

Keyword(s):

Clinical Significance ◽

Cancer Progression ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Published Data ◽

Protein Protein Interaction ◽

Cell Cycle Pathway ◽

Diagnostic Capacity ◽

Underlying Mechanisms

Abstract Background: KIAA1429, a member of the RNA methyltransferase complex, is involved in cancer progression. However, the clinical significance of KIAA1429 in osteosarcoma (OS) and the underlying mechanisms by which it contributes to disease progression remain unclear. Methods: The clinical significance of KIAA1429 in OS was evaluated based on the RT-qPCR, microarray, RNA sequencing, and published data. Two lentivirus-mediated KIAA1429-targeting siRNA constructs were transfected into SW1353 cells, and CCK-8 and flow cytometry assays were applied to investigate the biological function of KIAA1429 in OS cells. KIAA1429-related genes in OS were identified from lists of co-expressed genes (CEGs) and differentially expressed genes (DEGs). Functional enrichment analysis was employed to explore the potential mechanisms by which KIAA1429 contributes to the progression of OS.Results: The mRNA expression of KIAA1429 was notably overexpressed in 250 OS samples than 71 non-cancer samples (SMD=0.74). SROC curve analysis showed that KIAA1429 exhibits diagnostic capacity between OS samples and non-cancer samples (AUC=0.83). Survival analysis showed that overexpression of KIAA1429 was associated with shorter overall survival time. Knocking down KIAA1429 reduced the level of m6A methylation, inhibited proliferation, and accelerated apoptosis in OS cells. A total of 395 KIAA1429-related genes were identified, and were enriched in the cell cycle pathway. Protein–protein interaction (PPI) network analysis showed that CDK1, CCNA2, and CCNB1 were KIAA1429-related genes that act as major network hubs in OS. Conclusion: KIAA1429 plays an oncogenic role in OS and may facilitate the progression of OS through a mechanism involving the regulation of CDK1, CCNA2, and CCNB1.

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