A novel gene list identifies tumors with a stromal-mesenchymal phenotype and worse prognosis in gastric cancer
Tarih
2023Yazar
Demirkol Canlı, Seçil
Üner, Meral
Küçükkaraduman, Barış
Karaoğlu, Diren Arda
Işık, Aynur
Turhan, Nesrin
Akyol, Aytekin
Gömceli, İsmail
Güre, Ali Osmay
Üst veri
Tüm öğe kaydını gösterÖzet
Background: Molecular biomarkers that predict disease progression can help identify
tumor subtypes and shape treatment plans. In this study, we aimed to identify robust biomarkers
of prognosis in gastric cancer based on transcriptomic data obtained from primary gastric tumors.
Methods: Microarray, RNA sequencing, and single-cell RNA sequencing-based gene expression data
from gastric tumors were obtained from public databases. Freshly frozen gastric tumors (n = 42) and
matched FFPE (formalin-fixed, paraffin-embedded) (n = 40) tissues from a Turkish gastric cancer
cohort were used for quantitative real-time PCR and immunohistochemistry-based assessments of
gene expression, respectively. Results: A novel list of 20 prognostic genes was identified and used for
the classification of gastric tumors into two major tumor subgroups with differential stromal gene
expression (“Stromal-UP” (SU) and “Stromal-DOWN” (SD)). The SU group had a more mesenchymal
profile with an enrichment of extracellular matrix-related gene sets and a poor prognosis compared
to the SD group. Expression of the genes within the signature correlated with the expression of
mesenchymal markers ex vivo. A higher stromal content in FFPE tissues was associated with shorter
overall survival. Conclusions: A stroma-rich, mesenchymal subgroup among gastric tumors identifies
an unfavorable clinical outcome in all cohorts tested.