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Identification of Potential Key Genes Involved in Progression of Gastric Cancer Using Bioinformatics Analysis

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Novel therapeutic approaches for gastrointestinal malignancies

Part of the book series: Diagnostics and Therapeutic Advances in GI Malignancies ((DTAGIM))

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Abstract

Background: Despite the extensive effort on gastric cancer (GC) research and its achievement over the last decades, GC continues to remain the third leading cause of cancer mortality in the world. Detection of key genes involved in gastric cancer progression and prognosis leads to efficient approach to treat cancer.

Methods: Two datasets (PRJNA506381 and PRJNA438844) from Sequence Read Archive (SRA) database were analysed using available bioinformatics tools and differently expressed genes (DEGs) were identified. The enrichment, protein–protein interaction (PPI) network and survival analysis were carried out to unaware the potential genes responsible for GC progression.

Results: Totally, 227 upregulated and 247 downregulated genes were obtained, out of that overlapping 45 DEGs were selected for further analysis. Protein digestion and absorption and gastric acid secretion were the most enriched pathways. The PPI network was constructed by GeneMANIA and visualized in Cytoscape having 55 nodes and 689 interactions. Subsequently, NetworkAnalyzer plugin in Cytoscape was used and found 13 hub genes (MT1X, MT1E, MT1H, MT1F, MT1G, MT2A, MT1M, MT1A, MT1B, ATP4A, MT1HL1, PGC and CA9) based on high degree of connectivity ≥30. Further, eight highly connecting genes (KCNE2, CPA2, GIF, DRD5, CTSE, CLIC6, CHIA and LIPF) from the highly enriched modules were selected. Also, the prognostic value of the key genes was checked using Kaplan–Meier plotter, in that MT1X, MT1H, MT1E, ATP4A, KCNE2, CPA2, DRD5, CLIC6 and CHIA were associated with survival in overall survival of GC.

Conclusion: These results reveal that 13 hub genes and 8 highly connecting genes might contribute a major role in GC progression. Further, study of CAP2 could be utilised as potential prognostic biomarker.

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Abbreviations

ACRG :

Asian Cancer Research Group

ATP4A :

ATPase H+/K+ transporting subunit alpha

CA9 :

Carbonic anhydrase 9

CBLIF :

Cobalamin binding intrinsic factor

CHIA :

Chitinase acidic

CLIC6 :

Chloride intracellular channel 6

CNE-2:

CNE-2 enhancer upstream of SHOX

CPA2 :

Carboxypeptidase A2

CTSE :

Cathepsin E

DEGs :

Differently expressed genes

DRD5 :

Dopamine receptor D5

GC :

Gastric cancer

GO :

Gene ontology

HTS :

High throughput sequencing

KCNE2 :

Potassium voltage-gated channel subfamily E member 2

KEGG :

Kyoto Encyclopedia of Genes and Genomes

LIPF :

Lipase F, gastric type

MCODE :

Molecular complex detection

MT :

Metallothionein

NCBI :

National Centre for Biotechnology Information

NGS :

Next generation sequencing

PGC :

Progastrics in (pepsinogen C)

PPI :

Protein–protein interaction

SRA :

Sequence read archive

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Authors and Affiliations

  1. Centre for Bioinfiormatics, School of Life Sciences, Pondicherry University, Puducherry, India

    Vigneshwar Suriya Prakash Sinnarasan, Dahrii Paul, Leimarembi Devi Naorem, Mathavan Muthaiyan, Dinakara Rao Ampasala & Amouda Venkatesan

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  1. Vigneshwar Suriya Prakash Sinnarasan
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Editors and Affiliations

  1. Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA

    Ganji Purnachandra Nagaraju

  2. Department of Biotechnology, Dr. B.R. Ambedkar University, Srikakulam, Andhra Pradesh, India

    Sujatha Peela

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Sinnarasan, V.S.P., Paul, D., Naorem, L.D., Muthaiyan, M., Ampasala, D.R., Venkatesan, A. (2020). Identification of Potential Key Genes Involved in Progression of Gastric Cancer Using Bioinformatics Analysis. In: Nagaraju, G.P., Peela, S. (eds) Novel therapeutic approaches for gastrointestinal malignancies. Diagnostics and Therapeutic Advances in GI Malignancies. Springer, Singapore. https://doi.org/10.1007/978-981-15-5471-1_7

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