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Siavoshi A, Piran M, Sharifi‐Zarchi A, Ataellahi F. Integration of Gastric Cancer RNA-Seq Datasets Along With PPI Network Suggests That Nonhub Nodes Have the Potential to Become Biomarkers. Cancer Rep (Hoboken) 2025; 8:e70126. [PMID: 39854135 PMCID: PMC11757912 DOI: 10.1002/cnr2.70126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 12/22/2024] [Accepted: 01/15/2025] [Indexed: 01/26/2025] Open
Abstract
BACKGROUND The breakthrough discovery of novel biomarkers with prognostic and diagnostic value enables timely medical intervention for the survival of patients diagnosed with gastric cancer (GC). Typically, in studies focused on biomarker analysis, highly connected nodes (hubs) within the protein-protein interaction network (PPIN) are proposed as potential biomarkers. However, this study revealed an unexpected finding following the clustering of network nodes. Consequently, it is essential not to overlook weakly connected nodes (nonhubs) when determining suitable biomarkers from PPIN. METHODS AND RESULTS In this study, several potential biomarkers for GC were proposed based on the findings from RNA-sequencing (RNA-Seq) datasets, along with differential gene expression (DGE) analysis, PPINs, and weighted gene co-expression network analysis (WGCNA). Considering the overall survival (OS) analysis and the evaluation of expression levels alongside statistical parameters of the PPIN cluster nodes, it is plausible to suggest that THY1, CDH17, TGIF1, and AEBP1, categorized as nonhub nodes, along with ITGA5, COL1A1, FN1, and MMP2, identified as hub nodes, possess characteristics that render them applicable as biomarkers for the GC. Additionally, insulin-like growth factor (IGF)-binding protein-2 (IGFBP2), classified as a nonhub node, demonstrates a significant negative correlation with both groups within the same cluster. This observation underscores the conflicting findings regarding IGFBP2 in various cancer studies and enhances the potential of this gene to serve as a biomarker. CONCLUSION The findings of the current study not only identified the hubs and nonhubs that may serve as potential biomarkers for GC but also revealed a PPIN cluster that includes both hubs and nonhubs in conjunction with IGFBP2, thereby enhancing the understanding of the complex behavior associated with IGFBP2.
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Affiliation(s)
- Akram Siavoshi
- Department of Alborz Health Technology Development CenterAlborz University of Medical SciencesAlborzIran
| | - Mehran Piran
- Department of Medical Biotechnology, Drug Design and Bioinformatics Unit, Biotechnology Research CenterPasteur Institute of IranTehranIran
| | - Ali Sharifi‐Zarchi
- Department of Computer EngineeringSharif University of TechnologyTehranIran
| | - Fatemeh Ataellahi
- Department of Biology, College of SciencesShiraz UniversityShirazIran
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Akhtar A, Hameed Y, Ejaz S, Abdullah I. Identification of gastric cancer biomarkers through in-silico analysis of microarray based datasets. Biochem Biophys Rep 2024; 40:101880. [PMID: 39655267 PMCID: PMC11626535 DOI: 10.1016/j.bbrep.2024.101880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Revised: 11/02/2024] [Accepted: 11/18/2024] [Indexed: 12/12/2024] Open
Abstract
Gastric cancer is among the most prevalent cancers worldwide including in Pakistan. Late diagnosis of gastric cancer leads to reduced survival. The present study aimed to investigate biomarkers for early diagnosis and prognosis of gastric cancer. For this purpose, the ten microarray-based gene expression datasets (GSE54129, GSE79973, GSE161533, GSE103236, GSE33651, GSE19826, GSE118916, GSE112369, GSE13911, and GSE81948) were retrieved from GEO database and analyzed by GEO2R to identify differentially expressed genes. Datasets were arranged in subsets of different dataset combinations to identify common DEGs. The gene ontology and functional pathway enrichment analysis of common DEGs was performed by DAVID tool. Pan-cancer analysis was conducted by UALCAN database. Survival analysis of common DEGs was done by Kaplan-Meier plotter. A total of 71 common DEGs were identified in different combinations of datasets. Among them, only 5 DEGs namely ATP4B, ATP4A, CCKBR, KCNJ15, and KCNJ16 were detected to be common in all the datasets. The GO and pathway analysis represented that the identified DEGs are involved in gastric acid secretion and collecting duct acid secretion pathways. Further expression validation of these five genes using three additional datasets (GSE31811, GSE26899, and GSE26272) confirmed their differential expression in gastric cancer samples. The pan-cancer analysis also revealed aberrant expression of DEGs in various cancers. The survival analysis showed the association of these 5 DEGs with poor survival of gastric cancer patients. To conclude, this study revealed a panel of 5 genes, which can be employed as diagnostic and prognostic biomarkers of gastric cancer patients.
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Affiliation(s)
- Arbaz Akhtar
- Department of Biochemistry & Molecular Biology, Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB), The Islamia University of Bahawalpur, Bahawalpur, (63100), Pakistan
| | - Yasir Hameed
- Department of Biotechnology & Molecular Biology, Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB), The Islamia University of Bahawalpur, Bahawalpur, (63100), Pakistan
| | - Samina Ejaz
- Department of Biochemistry & Molecular Biology, Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB), The Islamia University of Bahawalpur, Bahawalpur, (63100), Pakistan
| | - Iqra Abdullah
- Department of Biochemistry & Molecular Biology, Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB), The Islamia University of Bahawalpur, Bahawalpur, (63100), Pakistan
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Tong X, Du J, Jiang Q, Wu Q, Zhao S, Chen S. Lenvatinib acts on platelet‑derived growth factor receptor β to suppress the malignant behaviors of gastric cancer cells. Oncol Lett 2024; 28:483. [PMID: 39170883 PMCID: PMC11338234 DOI: 10.3892/ol.2024.14616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 07/22/2024] [Indexed: 08/23/2024] Open
Abstract
Given the limited treatment options and high mortality rates associated with gastric cancer, there is a need to explore novel therapeutic options. The present study aimed to investigate the efficacy of lenvatinib, a multi-target tyrosine kinase inhibitor, in mitigating the progress of gastric cancer in vitro. Comprehensive analyses were conducted to assess the impact of lenvatinib on gastric cancer cells, focusing on the inhibition of viability, suppression of proliferation, induction of apoptosis and reduction of metastatic potential. The effects of lenvatinib on these activities were determined using 5-ethynyl-2'-deoxyuridine staining, colony formation assay, flow cytometry, western blotting, scratch assay and Transwell assay. In addition, bioinformatics analyses were employed to identify key regulatory targets of lenvatinib, with particular attention given to platelet-derived growth factor receptor β (PDGFRB). In addition, the effects of PDGFRB overexpression on the regulation of lenvatinib were explored. Lenvatinib demonstrated significant inhibitory effects on the viability, proliferation and metastatic capabilities of MKN45 and HGC27 gastric cancer cell lines. Bioinformatics analyses identified PDGFRB as a crucial target of lenvatinib, with its downregulation showing promise in enhancing overall survival rates of patients with gastric cancer. By contrast, PDGFRB overexpression reversed the effects of lenvatinib on cells. The present findings underscore the potential of lenvatinib as a promising therapeutic option in the treatment of gastric cancer. By elucidating its mechanism of action and identifying PDGFRB as a primary target, the present study may aid further clinical advancements.
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Affiliation(s)
- Xiaoyi Tong
- Graduate School, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, P.R. China
- Department of Pharmacy, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
| | - Jun Du
- Department of Nursing, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
| | - Qiaoling Jiang
- Department of Clinical Laboratory, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
| | - Qiaoli Wu
- Department of Pharmacy, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
| | - Shuxia Zhao
- Department of Pharmacy, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
| | - Shuhang Chen
- Department of Gastroenterology, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
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Mensah‐Bonsu M, Doss C, Gloster C, Muganda P. Gene expression analysis identifies hub genes and pathways distinguishing fatal from survivor outcomes of Ebola virus disease. FASEB Bioadv 2024; 6:298-310. [PMID: 39399477 PMCID: PMC11467745 DOI: 10.1096/fba.2024-00055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 06/06/2024] [Accepted: 07/02/2024] [Indexed: 10/15/2024] Open
Abstract
The Ebola virus poses a severe public health threat, yet understanding factors influencing disease outcomes remains incomplete. Our study aimed to identify critical pathways and hub genes associated with fatal and survivor Ebola disease outcomes. We analyzed differentially expressed hub genes (DEGs) between groups with fatal and survival outcomes, as well as a healthy control group. We conducted additional analysis to determine the functions and pathways associated with these DEGs. We found 13,198 DEGs in the fatal and 12,039 DEGs in the survival group compared to healthy controls, and 1873 DEGs in the acute fatal and survivor groups comparison. Upregulated DEGs in the comparison between the acute fatal and survivor groups were linked to ECM receptor interaction, complement and coagulation cascades, and PI3K-Akt signaling. Upregulated hub genes identified from the acute fatal and survivor comparison (FGB, C1QA, SERPINF2, PLAT, C9, SERPINE1, F3, VWF) were enriched in complement and coagulation cascades; the downregulated hub genes (IL1B, 1L17RE, XCL1, CXCL6, CCL4, CD8A, CD8B, CD3D) were associated with immune cell processes. Hub genes CCL2 and F2 were unique to fatal outcomes, while CXCL1, HIST1H4F, and IL1A were upregulated hub genes unique to survival outcomes compared to healthy controls. Our results demonstrate for the first time the association of EVD outcomes to specific hub genes and their associated pathways and biological processes. The identified hub genes and pathways could help better elucidate Ebola disease pathogenesis and contribute to the development of targeted interventions and personalized treatment for distinct EVD outcomes.
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Affiliation(s)
- Melvin Mensah‐Bonsu
- Applied Science and TechnologyNorth Carolina A&T State UniversityGreensboroNorth CarolinaUSA
| | - Christopher Doss
- Department of Electrical and Computer EngineeringNorth Carolina A&T State UniversityGreensboroNorth CarolinaUSA
| | - Clay Gloster
- Department of Computer Systems TechnologyNorth Carolina A&T State UniversityGreensboroNorth CarolinaUSA
| | - Perpetua Muganda
- Department of BiologyNorth Carolina A&T State UniversityGreensboroNorth CarolinaUSA
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Rohan P, dos Santos EC, Abdelhay E, Binato R. High Expression of THY1 in Intestinal Gastric Cancer as a Key Factor in Tumor Biology: A Poor Prognosis-Independent Marker Related to the Epithelial-Mesenchymal Transition Profile. Genes (Basel) 2023; 15:28. [PMID: 38254918 PMCID: PMC10815053 DOI: 10.3390/genes15010028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 12/15/2023] [Accepted: 12/19/2023] [Indexed: 01/24/2024] Open
Abstract
Gastric cancer (GC) is an important cancer-related death worldwide. Among its histological subtypes, intestinal gastric cancer (IGC) is the most common. A previous work showed that increased expression of the THY1 gene was associated with poor overall survival in IGC. Furthermore, it was shown that IGC tumor cells with high expression of THY1 have a greater capacity for tumorigenesis and metastasis in vitro. This study aimed to identify molecular differences between IGC with high and low expression of THY1. Using a feature selection method, a group of 35 genes were found to be the most informative gene set for THY1high IGC tumors. Through a classification model, these genes differentiate THY1high from THY1low tumors with 100% of accuracy both in the test subset and the independent test set. Additionally, this group of 35 genes correctly clustered 100% of the samples. An extensive validation of this potential molecular signature in multiple cohorts successfully segregated between THY1high and THY1low IGC tumors (>95%), proving to be independent of the gene expression quantification methodology. These genes are involved in central processes to tumor biology, such as the epithelial-mesenchymal transition (EMT) and remodeling of the tumor tissue composition. Moreover, patients with THY1high IGC demonstrated poor survival and a more advanced clinicopathological staging. Our findings revealed a molecular signature for IGC with high THY1 expression. This signature showed EMT and remodeling of the tumor tissue composition potentially related to the biology of IGC. Altogether, our results indicate that THY1high IGC tumors are a particular subset of tumors with a specific molecular and prognosis profile.
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Affiliation(s)
| | | | | | - Renata Binato
- Correspondence: ; Tel.: +55-21-3207-1874; Fax: +55-21-2509-2121
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Kuang F, Wang J, Wang BQ. Emergency exploratory laparotomy and radical gastrectomy in patients with gastric cancer combined with acute upper gastrointestinal bleeding. World J Gastrointest Surg 2023; 15:1423-1433. [PMID: 37555107 PMCID: PMC10405117 DOI: 10.4240/wjgs.v15.i7.1423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/07/2023] [Accepted: 05/24/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is a prevalent malignant tumor worldwide and ranks as the fourth leading cause of cancer-related mortality. Upper gastrointestinal bleeding (UGIB) is a frequent complication of GC. Radical gastrectomy and palliative therapy are widely used surgical procedures in the clinical management of GC. This study intends to probe the clinical efficacy and safety of radical gastrectomy and palliative therapy on the basis of exploratory laparotomy in patients with GC combined with UGIB, hoping to provide valuable information to aid patients in selecting the appropriate surgical intervention. AIM To investigate the clinical efficacy and safety of exploratory laparotomy + radical gastrectomy and palliative therapy in patients with GC and UGIB combined. METHODS A total of 89 GC patients admitted to the First Affiliated Hospital of the University of South China between July 2018 and July 2020 were selected as participants for this study. The 89 patients were divided into two groups: radical resection group (n = 46) treated with exploratory laparotomy + radical gastrectomy and Palliative group (n = 43) treated with palliative therapy. The study compared several variables between the two groups, including surgical duration, intraoperative blood transfusion volume, postoperative anal exhaust time, off-bed activity time, length of hospitalization, and incidence of complications such as duodenal stump rupture, anastomotic obstruction, and postoperative incision. Additionally, postoperative immune function indicators (including CD3+, CD4+, CD8+, CD4+/CD8+, and CD3+/HLADR+), immunoglobulin (IgG and IgM), tumor markers (CEA, CA199, and CA125), and inflammatory factors (IL-6, IL-17, and TNF-α) were assessed. The surgical efficacy and postoperative quality of life recovery were also evaluated. The patients were monitored for survival and tumor recurrence at 6 mo, 1 year, and 2 years post-surgery. RESULTS The results indicated that the duration of operation time and postoperative hospitalization did not differ between the two surgical procedures. However, patients in the radical resection group exhibited shorter intraoperative blood loss, anus exhaust time, off-bed activity time, and inpatient activity time than those in the Palliative group. Although there was no substantial difference in the occurrence of postoperative complications, such as duodenal stump rupture and anastomotic obstruction, between the radical resection group and Palliative group (P > 0.05), the radical resection group exhibited higher postoperative immune function indicators (including CD3+, CD4+, CD8+, etc.) and immunoglobulin levels (IgG, IgM) than the Palliative group, while tumor markers and inflammatory factors levels were lower than those in the radical resection group. Additionally, surgical efficacy, postoperative quality of life, and postoperative survival rates were higher in patients who underwent radical gastrectomy than in those who underwent palliative therapy. Moreover, the probability of postoperative tumor recurrence was lower in the radical gastrectomy group compared to the palliative therapy group, and these differences were all statistically significant (P < 0.05). CONCLUSION Compared to palliative therapy, exploratory laparotomy + radical gastrectomy can improve immune function, reduce the levels of tumor markers and inflammatory factors, improve surgical efficacy, promote postoperative quality of life recovery, enhance survival rates, and attenuate the probability of tumor recurrence.
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Affiliation(s)
- Feng Kuang
- Department of Emergency, The First Affiliated Hospital of University of South China, Hengyang 421001, Hunan Province, China
| | - Jian Wang
- Department of Emergency, The First Affiliated Hospital of University of South China, Hengyang 421001, Hunan Province, China
| | - Bai-Qi Wang
- Department of Radiation Oncology, The Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan Province, China
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Wang J, Liu D, Xie Y. GHRL as a prognostic biomarker correlated with immune infiltrates and progression of precancerous lesions in gastric cancer. Front Oncol 2023; 13:1142017. [PMID: 37469414 PMCID: PMC10353738 DOI: 10.3389/fonc.2023.1142017] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 06/12/2023] [Indexed: 07/21/2023] Open
Abstract
Objective Ghrelin is a protein that regulate appetite and energy balance in the human body, which is encoded by the ghrelin prepropeptide gene (GHRL). GHRL is linked with carcinogenesis and immune regulation. However, the correlation of GHRL to prognosis and tumor-infiltrating lymphocytes in gastric cancer (GC) remains unclear. Methods In this study, we assessed the transcriptional expression, prognosis, and different clinicopathological features about GHRL and the correlation between GHRL and tumor infiltration immune cells in GC patients based on the data published in the following databases: TIMER, GEPIA, GEO, STRING, UALCAN, TISIDB, and Kaplan-Meier Plotter. Furthermore, R software analysis for GC Correa' cascade was also provided. Finally, GHRL expression in GC tissues was assayed using quantitative real-time polymerase chain reaction and immunohistochemistry. Results We found that GHRL expression in GC samples was lower than in normal samples and verified by quantitative PCR (qPCR) and immunohistochemistry. However, sample type, cancer stage, and worse survival were correlated to high GHRL expression. We also found that the expression of GHRL in dysplasia was significantly lower than that in CNAG and in GC. High GHRL expression was connected with immunomodulators, chemokines, and infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in GC. Conclusions GHRL is a prognostic biomarker for GC patients, and it is correlated with progression of precancerous lesions in GC. It might lead to poor prognosis by regulating tumor immune microenvironment. Studies are important to explore therapeutic targeting GHRL in the future.
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De Silva K, Demmer RT, Jönsson D, Mousa A, Forbes A, Enticott J. Highly perturbed genes and hub genes associated with type 2 diabetes in different tissues of adult humans: a bioinformatics analytic workflow. Funct Integr Genomics 2022; 22:1003-1029. [PMID: 35788821 PMCID: PMC9255467 DOI: 10.1007/s10142-022-00881-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 06/19/2022] [Accepted: 06/24/2022] [Indexed: 11/28/2022]
Abstract
Type 2 diabetes (T2D) has a complex etiology which is not yet fully elucidated. The identification of gene perturbations and hub genes of T2D may deepen our understanding of its genetic basis. We aimed to identify highly perturbed genes and hub genes associated with T2D via an extensive bioinformatics analytic workflow consisting of five steps: systematic review of Gene Expression Omnibus and associated literature; identification and classification of differentially expressed genes (DEGs); identification of highly perturbed genes via meta-analysis; identification of hub genes via network analysis; and downstream analysis of highly perturbed genes and hub genes. Three meta-analytic strategies, random effects model, vote-counting approach, and p value combining approach, were applied. Hub genes were defined as those nodes having above-average betweenness, closeness, and degree in the network. Downstream analyses included gene ontologies, Kyoto Encyclopedia of Genes and Genomes pathways, metabolomics, COVID-19-related gene sets, and Genotype-Tissue Expression profiles. Analysis of 27 eligible microarrays identified 6284 DEGs (4592 downregulated and 1692 upregulated) in four tissue types. Tissue-specific gene expression was significantly greater than tissue non-specific (shared) gene expression. Analyses revealed 79 highly perturbed genes and 28 hub genes. Downstream analyses identified enrichments of shared genes with certain other diabetes phenotypes; insulin synthesis and action-related pathways and metabolomics; mechanistic associations with apoptosis and immunity-related pathways; COVID-19-related gene sets; and cell types demonstrating over- and under-expression of marker genes of T2D. Our approach provided valuable insights on T2D pathogenesis and pathophysiological manifestations. Broader utility of this pipeline beyond T2D is envisaged.
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Affiliation(s)
- Kushan De Silva
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton, 3168, Australia.
| | - Ryan T Demmer
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.,Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Daniel Jönsson
- Department of Periodontology, Faculty of Odontology, Malmö University, 21119, Malmö, Sweden.,Department of Clinical Sciences, Lund University, 21428, Malmö, Sweden
| | - Aya Mousa
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton, 3168, Australia
| | - Andrew Forbes
- Biostatistics Unit, Division of Research Methodology, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Melbourne, 3004, Australia
| | - Joanne Enticott
- Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Clayton, 3168, Australia
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Chivu-Economescu M, Necula LG, Matei L, Dragu D, Bleotu C, Sorop A, Herlea V, Dima S, Popescu I, Diaconu CC. Collagen Family and Other Matrix Remodeling Proteins Identified by Bioinformatics Analysis as Hub Genes Involved in Gastric Cancer Progression and Prognosis. Int J Mol Sci 2022; 23:3214. [PMID: 35328635 PMCID: PMC8950589 DOI: 10.3390/ijms23063214] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 03/14/2022] [Accepted: 03/15/2022] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer has remained in the top five cancers for over ten years, both in terms of incidence and mortality due to the shortage of biomarkers for disease follow-up and effective therapies. Aiming to fill this gap, we performed a bioinformatics assessment on our data and two additional GEO microarray profiles, followed by a deep analysis of the 40 differentially expressed genes identified. PPI network analysis and MCODE plug-in pointed out nine upregulated hub genes coding for proteins from the collagen family (COL12A1, COL5A2, and COL10A1) or involved in the assembly (BGN) or degradation of collagens (CTHRC1), and also associated with cell adhesion (THBS2 and SPP1) and extracellular matrix degradation (FAP, SULF1). Those genes were highly upregulated at the mRNA and protein level, the increase being correlated with pathological T stages. The high expression of BGN (p = 8 × 10-12), THBS2 (p = 1.2 × 10-6), CTHRC1 (p = 1.1 × 10-4), SULF1 (p = 3.8 × 10-4), COL5A1 (p = 1.3 × 10-4), COL10A1 (p = 5.7 × 10-4), COL12A1 (p = 2 × 10-3) correlated with poor overall survival and an immune infiltrate based especially on immunosuppressive M2 macrophages (p-value range 4.82 × 10-7-1.63 × 10-13). Our results emphasize that these genes could be candidate biomarkers for GC progression and prognosis and new therapeutic targets.
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Affiliation(s)
- Mihaela Chivu-Economescu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania; (L.G.N.); (L.M.); (D.D.); (C.B.); (C.C.D.)
| | - Laura G. Necula
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania; (L.G.N.); (L.M.); (D.D.); (C.B.); (C.C.D.)
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania; (V.H.); (I.P.)
| | - Lilia Matei
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania; (L.G.N.); (L.M.); (D.D.); (C.B.); (C.C.D.)
| | - Denisa Dragu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania; (L.G.N.); (L.M.); (D.D.); (C.B.); (C.C.D.)
| | - Coralia Bleotu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania; (L.G.N.); (L.M.); (D.D.); (C.B.); (C.C.D.)
| | - Andrei Sorop
- Center of Excellence for Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania; (A.S.); (S.D.)
| | - Vlad Herlea
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania; (V.H.); (I.P.)
- Department of Pathology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Simona Dima
- Center of Excellence for Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania; (A.S.); (S.D.)
- Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Irinel Popescu
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania; (V.H.); (I.P.)
- Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Carmen C. Diaconu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania; (L.G.N.); (L.M.); (D.D.); (C.B.); (C.C.D.)
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De Silva K, Demmer RT, Jönsson D, Mousa A, Forbes A, Enticott J. A data-driven biocomputing pipeline with meta-analysis on high throughput transcriptomics to identify genome-wide miRNA markers associated with type 2 diabetes. Heliyon 2022; 8:e08886. [PMID: 35169647 PMCID: PMC8829580 DOI: 10.1016/j.heliyon.2022.e08886] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 11/23/2021] [Accepted: 01/29/2022] [Indexed: 12/12/2022] Open
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