Forecasting Gastric Cancer Diagnosis, Prognosis, and Drug Repurposing with Novel Gene Expression Signatures
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Tarih
2022
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Mary Ann Liebert, Inc
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Gastric cancer (GC) is a prevalent disease worldwide with high mortality and poor treatment success. Early diagnosis of GC and forecasting of its prognosis with the use of biomarkers are directly relevant to achieve both personalized/precision medicine and innovation in cancer therapeutics. Gene expression signatures offer one of the promising avenues of research in this regard, as well as guiding drug repurposing analyses in cancers. Using publicly accessible gene expression datasets from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA), we report here original findings on co-expressed gene modules that are differentially expressed between 133 GC samples and 46 normal tissues, and thus hold potential for novel diagnostic candidates for GC. Furthermore, we found two co-expressed gene modules were significantly associated with poor survival outcomes revealed by survival analysis of the RNA-Seq TCGA datasets. We identified STAT6 (signal transducer and activator of transcription 6) as a key regulator of the identified gene modules. Finally, potential therapeutic drugs that may target and reverse the expression of the identified altered gene modules examined for drug repurposing analyses and the unraveled compounds were further investigated in the literature by the text mining method. Accordingly, we found several repurposed drug candidates, including Trichostatin A, Vorinostat, Parthenolide, Panobinostat, Brefeldin A, Belinostat, and Danusertib. Through text mining analysis and literature search validation, Belinostat and Danusertib were suggested as possible novel drug candidates for GC treatment. These findings collectively inform multiple aspects of GC medical management, including its precision diagnosis, forecasting of possible outcomes, and drug repurposing for innovation in GC medicines in the future.
Açıklama
Anahtar Kelimeler
drug repurposing, gastric cancer, genomics, prognostic biomarkers, systems biology
Kaynak
Omics-A Journal of Integrative Biology
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
26
Sayı
1
