Elucidating the pathogenesis of esophageal adenocarcinoma through meta-analysis of public data.

71 Background: Esophageal adenocarcinoma (EAC) is the sixth most common cause of cancer-related deaths worldwide. It commonly arises in the setting of reflux disease and Barett’s esophagus. It remains incurable and holds a poor prognosis. Dissecting the genetic signature of EAC can pave new therapeutic avenues. Methods: We employed our Search Tag Analyze Resource (STARGEO) platform to conduct meta-analysis using the National Center for Biotechnology’s (NCBI) Gene Expression Omnibus (GEO). We tagged 151 tumor samples from EAC patients and 62 normal esophageal samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis, restricting genes that showed statistical significance (p < 0.05) and an absolute experimental log ratio greater than 0.15 between tumor and control. Results: Our analysis revealed granulocyte adhesion and diapedesis and FXR/RXR signaling as top canonical pathways. TGFB1, TNF, and beta-estradiol were top upstream regulators with predicted activation. TGFB1 and TNF expression have been correlated with poor prognosis in EAC. Also, beta-estradiol has tumorigenic activity in several cancers but has not been investigated in EAC. Among the top upregulated genes were oncogenic genes such as tetraspanin 8, the antiapoptotic factor OLFM4, and the protease cathepsin E (CTSE). SPINK1, a trypsin inhibitor with recently suggested role in cancer, and the choline transporter SLC44A4, a drug target for pancreatic cancer, were also upregulated. The most downregulated genes included alcohol dehydrogenase 7, associated with EAC in alcohol-drinkers, and the pro-apoptotic gene CRCT1. We also found downregulation of the serine peptidase inhibitor SPINK7. SPINK7 is involved in maintaining epithelial-barrier integrity and is implicated in eosinophilic esophagitis pathogenesis. Lastly, there was downregulation of the candidate tumor suppressor gene transglutaminase 3. Conclusions: Despite screening efforts, EAC incidence and mortality continues to increase as does the need for better treatment. This meta-analysis defines the significant gene expression changes within causal disease processes to provide markers for detection, prognostic insight, and therapeutic value for EAC.

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High Moesin Expression Is a Predictor of Poor Prognosis of Breast Cancer: Evidence From a Systematic Review With Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.650488 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaoli Hu ◽

Yang Liu ◽

Zhitong Bing ◽

Qian Ye ◽

Chengcheng Li

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Systematic Review ◽

Cancer Patients ◽

Poor Prognosis ◽

Data Extraction ◽

Meta Analysis ◽

Gene Expression Omnibus ◽

Breast Cancer Patients ◽

Node Metastases

Owing to metastases and drug resistance, the prognosis of breast cancer is still dismal. Therefore, it is necessary to find new prognostic markers to improve the efficacy of breast cancer treatment. Literature shows a controversy between moesin (MSN) expression and prognosis in breast cancer. Here, we aimed to conduct a systematic review and meta-analysis to evaluate the prognostic relationship between MSN and breast cancer. Literature retrieval was conducted in the following databases: PubMed, Web of Science, Embase, and Cochrane. Two reviewers independently performed the screening of studies and data extraction. The Gene Expression Omnibus (GEO) database including both breast cancer gene expression and follow-up datasets was selected to verify literature results. The R software was employed for the meta-analysis. A total of 9 articles with 3,039 patients and 16 datasets with 2,916 patients were ultimately included. Results indicated that there was a significant relationship between MSN and lymph node metastases (P < 0.05), and high MSN expression was associated with poor outcome of breast cancer patients (HR = 1.99; 95% CI 1.73–2.24). In summary, there is available evidence to support that high MSN expression has valuable importance for the poor prognosis in breast cancer patients.Systematic Review Registrationhttps://inplasy.com/inplasy-2020-8-0039/.

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Dissecting novel mechanisms of hepatitis B virus-related hepatocellular carcinoma using meta-analysis of public data.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.333 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 333-333

Author(s):

Jihad Aljabban ◽

Michael Rohr ◽

Saad A Syed ◽

Eli Cohen ◽

Naima Hashi ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Hepatitis B ◽

Meta Analysis ◽

Causal Analysis ◽

Gene Expression Omnibus ◽

Regulatory Proteins ◽

Public Data ◽

Viral Regulatory Proteins

333 Background: Hepatitis B is a cause of hepatocellular carcinoma (HCC) globally, irrespective of viral loads. Interestingly, this process is not necessarily mediated through cirrhosis and may in fact involve oncogenic processes. Prior studies have suggested specific oncogenic gene expression pathways affected by viral regulatory proteins. Thus, identifying these genes and associated pathways could highlight predictive factors for HCC transformation, and has implications in early diagnosis and treatment. Methods: We employed our Search, Tag, Analyze, Resource (STARGEO) platform to conduct a meta-analysis of public data from NCBI's Gene Expression Omnibus. We performed meta-analysis consisting of 155 tumor samples compared against 185 adjacent non-tumor samples. We present the results from the meta-analysis in Ingenuity Pathway Analysis. Results:Our analysis revealed LXR/RXR activation, LPS-IL-1 mediation inhibition of RXR, and FXR/RXR activation as top canonical pathways amongst others. Top upstream regulators identified included the Ras family gene RABL6. The role of RABL6 in oncogenesis is beginning to unfold but its specific role in HBV-related HCC remains undefined. Our causal analysis suggests RABL6 mediates pathogenesis of HBV-related HCC through promotion of genes related to cell division, epigenetic regulation, and Akt signaling. Additionally, HOXA10 was a top upstream regulator and was strongly upregulated in our analysis. While described in other cancer, HOXA10 has not been well documented in HBV-related HCC and our causal analysis suggests it mediates pathogenesis through downregulation of tumor suppressors and its protective effect from oxidative stress. Conclusions: This meta-analysis describes possible role of viral regulatory proteins such as RABL6 and HOXA10 in the pathogenesis of HBV -related HCC. Further prospective studies are needed to confirm our findings.

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Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis

PLoS ONE ◽

10.1371/journal.pone.0258187 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258187

Author(s):

David Z. Allen ◽

Jihad Aljabban ◽

Dustin Silverman ◽

Sean McDermott ◽

Ross A. Wanner ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Structural Integrity ◽

Tissue Injury ◽

Remission Rate ◽

Meta Analysis ◽

Statistical Significance ◽

Interleukin 1 ◽

Gene Expression Omnibus ◽

Ncbi Gene Expression Omnibus ◽

Log Ratio

Background Nasopharyngeal carcinoma (NPC) is a cancer of epithelial origin with a high incidence in certain populations. While NPC has a high remission rate with concomitant chemoradiation, recurrences are frequent, and the downstream morbidity of treatment is significant. Thus, it is imperative to find alternative therapies. Methods We employed a Search Tag Analyze Resource (STARGEO) platform to conduct a meta-analysis using the National Center for Biotechnology’s (NCBI) Gene Expression Omnibus (GEO) to define NPC pathogenesis. We identified 111 tumor samples and 43 healthy nasopharyngeal epithelium samples from NPC public patient data. We analyzed associated signatures in Ingenuity Pathway Analysis (IPA), restricting genes that showed statistical significance (p<0.05) and an absolute experimental log ratio greater than 0.15 between disease and control samples. Results Our meta-analysis identified activation of lipopolysaccharide (LPS)-induced tissue injury in NPC tissue. Additionally, interleukin-1 (IL-1) and SB203580 were the top upstream regulators. Tumorigenesis-related genes such as homeobox A10 (HOXA10) and prostaglandin-endoperoxide synthase 2 (PTGS2 or COX-2) as well as those associated with extracellular matrix degradation, such as matrix metalloproteinases 1 and 3 (MMP-1, MMP-3) were also upregulated. Decreased expression of genes that encode proteins associated with maintaining healthy nasal respiratory epithelium structural integrity, including sentan-cilia apical structure protein (SNTN) and lactotransferrin (LTF) was documented. Importantly, we found that etanercept inhibits targets upregulated in NPC and LPS induction, such as MMP-1, PTGS2, and possibly MMP-3. Conclusions Our analysis illustrates that nasal epithelial barrier dysregulation and maladaptive immune responses are key components of NPC pathogenesis along with LPS-induced tissue damage.

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Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas

Cancers ◽

10.3390/cancers13010158 ◽

2021 ◽

Vol 13 (1) ◽

pp. 158

Author(s):

Valentina Condelli ◽

Giovanni Calice ◽

Alessandra Cassano ◽

Michele Basso ◽

Maria Grazia Rodriquenz ◽

...

Keyword(s):

Gene Expression ◽

Poor Prognosis ◽

Cpg Island ◽

Colon Adenocarcinoma ◽

Gene Signature ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Cpg Island Methylator Phenotype ◽

Prognostic Information ◽

Global Methylation

Epigenetics is involved in tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that the DNA methylation profiling may predict the clinical behavior of metastatic CRCs (mCRCs). The global methylation profile of two human mCRC subgroups with significantly different outcome was analyzed and compared with gene expression and methylation data from The Cancer Genome Atlas COlon ADenocarcinoma (TCGA COAD) and the NCBI GENE expression Omnibus repository (GEO) GSE48684 mCRCs datasets to identify a prognostic signature of functionally methylated genes. A novel epigenetic signature of eight hypermethylated genes was characterized that was able to identify mCRCs with poor prognosis, which had a CpG-island methylator phenotype (CIMP)-high and microsatellite instability (MSI)-like phenotype. Interestingly, methylation events were enriched in genes located on the q-arm of chromosomes 13 and 20, two chromosomal regions with gain/loss alterations associated with adenoma-to-carcinoma progression. Finally, the expression of the eight-genes signature and MSI-enriching genes was confirmed in oxaliplatin- and irinotecan-resistant CRC cell lines. These data reveal that the hypermethylation of specific genes may provide prognostic information that is able to identify a subgroup of mCRCs with poor prognosis.

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Prospective validation in epithelial tumors of a gene expression predictor of liver metastasis derived from uveal melanoma

Scientific Reports ◽

10.1038/s41598-019-52841-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Petros Tsantoulis ◽

Mauro Delorenzi ◽

Ivan Bièche ◽

Sophie Vacher ◽

Pascale Mariani ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Colorectal Cancer ◽

Liver Metastasis ◽

Uveal Melanoma ◽

Meta Analysis ◽

Prognostic Score ◽

Penalized Regression ◽

Breast Cancer Patients ◽

Public Data

AbstractPredicting the risk of liver metastasis can have important prognostic and therapeutic implications, given the availability of liver-directed therapy. Uveal melanoma has a striking predisposition for liver metastasis despite the absence of anatomical proximity. Understanding its biology may uncover factors promoting liver metastasis in other malignancies. We quantified gene expression by RNAseq in 76 uveal melanomas and combined with public data in a meta-analysis of 196 patients. The meta-analysis of uveal melanoma gene expression identified 63 genes which remained prognostic after adjustment for chromosome 3 status. Two genes, PTP4A3 and JPH1, were selected by L1-penalized regression and combined in a prognostic score. The score predicted liver-specific relapse in a public pan-cancer dataset and in two public colorectal cancer datasets. The score varied between colorectal consensus molecular subtypes (CMS), as did the risk of liver relapse, which was lowest in CMS1. Additional prospective validation was done by real-time PCR in 463 breast cancer patients. The score was significantly correlated with liver relapse in hormone receptor positive tumors. In conclusion, the expression of PTP4A3 and JPH1 correlates with risk of liver metastasis in colorectal cancer and breast cancer. The underlying biological mechanism is an interesting area for further research.

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ExAtlas: An interactive online tool for meta-analysis of gene expression data

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720015500195 ◽

2015 ◽

Vol 13 (06) ◽

pp. 1550019 ◽

Cited By ~ 37

Author(s):

Alexei A. Sharov ◽

David Schlessinger ◽

Minoru S. H. Ko

Keyword(s):

Gene Expression ◽

Gene Ontology ◽

Gene Expression Data ◽

Fixed Effects ◽

Expression Profiles ◽

Meta Analysis ◽

Data Sets ◽

Expression Data ◽

Gene Set ◽

Public Data

We have developed ExAtlas, an on-line software tool for meta-analysis and visualization of gene expression data. In contrast to existing software tools, ExAtlas compares multi-component data sets and generates results for all combinations (e.g. all gene expression profiles versus all Gene Ontology annotations). ExAtlas handles both users’ own data and data extracted semi-automatically from the public repository (GEO/NCBI database). ExAtlas provides a variety of tools for meta-analyses: (1) standard meta-analysis (fixed effects, random effects, z-score, and Fisher’s methods); (2) analyses of global correlations between gene expression data sets; (3) gene set enrichment; (4) gene set overlap; (5) gene association by expression profile; (6) gene specificity; and (7) statistical analysis (ANOVA, pairwise comparison, and PCA). ExAtlas produces graphical outputs, including heatmaps, scatter-plots, bar-charts, and three-dimensional images. Some of the most widely used public data sets (e.g. GNF/BioGPS, Gene Ontology, KEGG, GAD phenotypes, BrainScan, ENCODE ChIP-seq, and protein–protein interaction) are pre-loaded and can be used for functional annotations.

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682 Investigating the Pathogenesis of Ulcerative Colitis Through Meta-Analysis of Gene Expression Omnibus Data

The American Journal of Gastroenterology ◽

10.14309/01.ajg.0000592264.60606.11 ◽

2019 ◽

Vol 114 (1) ◽

pp. S400-S401

Author(s):

Kamal Khorfan ◽

Jihad Aljabban ◽

Merve Gurakar ◽

Hajra Khan ◽

Nabeal Aljabban ◽

...

Keyword(s):

Gene Expression ◽

Ulcerative Colitis ◽

Meta Analysis ◽

Gene Expression Omnibus

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OSmfs: An Online Interactive Tool to Evaluate Prognostic Markers for Myxofibrosarcoma

Genes ◽

10.3390/genes11121523 ◽

2020 ◽

Vol 11 (12) ◽

pp. 1523

Author(s):

Huimin Li ◽

Longxiang Xie ◽

Qiang Wang ◽

Yifang Dang ◽

Xiaoxiao Sun ◽

...

Keyword(s):

Gene Expression ◽

Poor Prognosis ◽

Analysis Data ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Prognostic Biomarkers ◽

Rank Test ◽

Web Tool ◽

Kaplan Meier ◽

Cox Analysis

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.

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Host–Viral Interactions Revealed among Shared Transcriptomics Signatures of ARDS and Thrombosis: A Clue into COVID-19 Pathogenesis

TH Open ◽

10.1055/s-0040-1721706 ◽

2020 ◽

Vol 04 (04) ◽

pp. e403-e412

Author(s):

Aastha Mishra ◽

Shankar Chanchal ◽

Mohammad Z. Ashraf

Keyword(s):

Gene Expression ◽

Virus Disease ◽

Meta Analysis ◽

Random Effect ◽

Enrichment Analysis ◽

Coagulation Factors ◽

Gene Expression Omnibus ◽

Endothelial Damage ◽

Pathway Enrichment Analysis ◽

Hub Genes

AbstractSevere novel corona virus disease 2019 (COVID-19) infection is associated with a considerable activation of coagulation pathways, endothelial damage, and subsequent thrombotic microvascular injuries. These consistent observations may have serious implications for the treatment and management of this highly pathogenic disease. As a consequence, the anticoagulant therapeutic strategies, such as low molecular weight heparin, have shown some encouraging results. Cytokine burst leading to sepsis which is one of the primary reasons for acute respiratory distress syndrome (ARDS) drive that could be worsened with the accumulation of coagulation factors in the lungs of COVID-19 patients. However, the obscurity of this syndrome remains a hurdle in making decisive treatment choices. Therefore, an attempt to characterize shared biological mechanisms between ARDS and thrombosis using comprehensive transcriptomics meta-analysis is made. We conducted an integrated gene expression meta-analysis of two independently publicly available datasets of ARDS and venous thromboembolism (VTE). Datasets GSE76293 and GSE19151 derived from National Centre for Biotechnology Information–Gene Expression Omnibus (NCBI-GEO) database were used for ARDS and VTE, respectively. Integrative meta-analysis of expression data (INMEX) tool preprocessed the datasets and effect size combination with random effect modeling was used for obtaining differentially expressed genes (DEGs). Network construction was done for hub genes and pathway enrichment analysis. Our meta-analysis identified a total of 1,878 significant DEGs among the datasets, which when subjected to enrichment analysis suggested inflammation–coagulation–hypoxemia convolutions in COVID-19 pathogenesis. The top hub genes of our study such as tumor protein 53 (TP53), lysine acetyltransferase 2B (KAT2B), DExH-box helicase 9 (DHX9), REL-associated protein (RELA), RING-box protein 1 (RBX1), and proteasome 20S subunit beta 2 (PSMB2) gave insights into the genes known to be participating in the host–virus interactions that could pave the way to understand the various strategies deployed by the virus to improve its replication and spreading.

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The role of FOXD2-AS1 in cancer: a comprehensive study based on data mining and published articles

Bioscience Reports ◽

10.1042/bsr20190372 ◽

2020 ◽

Vol 40 (11) ◽

Author(s):

Yongping Zhang ◽

Chaojie Liang ◽

Yu Zhang ◽

Zhinmin Wang ◽

Ruihuan Li ◽

...

Keyword(s):

Gene Expression ◽

Cancer Patients ◽

Tumor Size ◽

Meta Analysis ◽

Disease Free Survival ◽

Gene Expression Omnibus ◽

Tnm Stage ◽

Potential Biomarker ◽

Tcga Dataset

Abstract Background and aims: Long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is aberrantly expressed in various cancers and associated with cancer progression. A comprehensive meta-analysis was performed based on published literature and data in the Gene Expression Omnibus database, and then the Cancer Genome Atlas (TCGA) dataset was used to assess the clinicopathological and prognostic value of FOXD2-AS1 in cancer patients. Methods: Gene Expression Omnibus databases of microarray data and published articles were used for meta-analysis, and TCGA dataset was also explored using the GEPIA analysis program. Hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the role of FOXD2-AS1 in cancers. Results: This meta-analysis included 21 studies with 2391 patients and 25 GEO datasets with 3311 patients. The pooled HRs suggested that highly expressed FOXD2-AS1 expression was correlated with poor overall survival (OS) and disease-free survival (DFS). Similar results were obtained by analysis of TCGA data for 9502 patients. The pooled results also indicated that FOXD2-AS1 expression was associated with bigger tumor size and advanced TNM stage, but was not related to age, gender, differentiation and lymph node metastasis. Conclusion: The present study demonstrated that FOXD2-AS1 is closely related to tumor size and TNM stage. Additionally, increased FOXD2-AS1 was a risk factor of OS and DFS in cancer patients, suggesting FOXD2-AS1 may be a potential biomarker in human cancers.

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