Single-cell transcriptomic analysis reveals crucial oncogenic signatures and its associative cell types involved in gastric cancer.

Drug–gene interaction Gastric cancer Ligand–receptor interaction Oncogenes Single-cell RNA-seq analysis Survival analysis Trajectory inference

Journal

Medical oncology (Northwood, London, England)
ISSN: 1559-131X
Titre abrégé: Med Oncol
Pays: United States
ID NLM: 9435512

Informations de publication

Date de publication:
23 Sep 2023
Historique:
received: 01 08 2023
accepted: 28 08 2023
medline: 25 9 2023
pubmed: 23 9 2023
entrez: 23 9 2023
Statut: epublish

Résumé

The intricate association of oncogenic markers negatively impacts accurate gastric cancer diagnosis and leads to the proliferation of mortality rate. Molecular heterogeneity is inevitable in determining gastric cancer's progression state with multiple cell types involved. Identification of pathogenic gene signatures is imperative to understand the disease's etiology. This study demonstrates a systematic approach to identifying oncogenic gastric cancer genes linked with different cell types. The raw counts of adjacent normal and gastric cancer samples are subjected to a quality control step. The dimensionality reduction and multidimensional clustering are performed using Principal Component Analysis (PCA) and Uniform Manifold Approximation and Projection (UMAP) techniques. The adjacent normal and gastric cancer sample cell clusters are annotated with the Human Primary Cell Atlas database using the "SingleR." Cellular state transition between the distinct groups is characterized using trajectory analysis. The ligand-receptor interaction between Vascular Endothelial Growth Factor (VEGF) and cell clusters unveils crucial molecular pathways in gastric cancer progression. Chondrocytes, Smooth muscle cells, and fibroblast cell clusters contain genes contributing to poor survival rates based on hazard ratio during survival analysis. The GC-related oncogenic signatures are isolated by comparing the gene set with the DisGeNET database. Twelve gastric cancer biomarkers (SPARC, KLF5, HLA-DRB1, IGFBP3, TIMP3, LGALS1, IGFBP6, COL18A1, F3, COL4A1, PDGFRB, COL5A2) are linked with gastric cancer and further validated through gene set enrichment analysis. Drug-gene interaction found PDGFRB, interacting with various anti-cancer drugs, as a potential inhibitor for gastric cancer. Further investigations on these molecular signatures will assist the development of precision therapeutics, promising longevity among gastric cancer patients.

Identifiants

pubmed: 37740827
doi: 10.1007/s12032-023-02174-8
pii: 10.1007/s12032-023-02174-8
doi:

Substances chimiques

Receptor, Platelet-Derived Growth Factor beta EC 2.7.10.1
Vascular Endothelial Growth Factor A 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

305

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Karthik Sekaran (K)

School of Biosciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India.

Rinku Polachirakkal Varghese (RP)

School of Biosciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India.

Hatem Zayed (H)

Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha, Qatar.

Achraf El Allali (A)

African Genome Center, Mohammed VI Polytechnic University, Ben Guerir, Morocco.

C George Priya Doss (C)

School of Biosciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India. georgepriyadoss@vit.ac.in.

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