یکشنبه 26 مهر 1405
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Ethics code: IR.ACECR.ROYAN.REC.1399.121
چکیده: (18 مشاهده)
Background and Objective: Gastric cancer (GC) cell lines serve as important models for studying GC biology and therapy development. Their diversity reflects tumor heterogeneity, which can result in differences in signaling pathways and experimental outcomes. Here, we compared the transcriptomic profiles of GC cell lines to identify variations in their signaling pathways and biological processes.
Materials and Methods: To this end, we integrated our bulk RNA-seq raw count data from three HGC-27 GC cell line replicates with transcriptomic data from 18 independent public studies. The resulting dataset comprised 42 RNA-seq profiles, including 39 profiles from eight GC cell lines (HGC-27, MKN-45, KATO III, SNU-16, AGS, SNU-601, MKN-7, and FU97) and three profiles from the normal gastric cell line GES-1. CenTFinder was then used to identify active co-expression modules, followed by pathway, GO enrichment, and RcisTarget analyses to characterize biological functions and potential master regulators.
Results: We identified 14 co-expression modules. FU97, a gastric hepatoid adenocarcinoma cell line, showed enrichment of liver-associated metabolic processes, including “very-low-density lipoprotein particle remodeling” (Fisher’s exact test = 9.6 × 10⁻⁵), supporting the biological relevance of the identified modules (GSVA score = 0.89). Distinct module activity patterns were observed across cell lines, including significant enrichment of the “hsa00190-Oxidative Phosphorylation” pathway in HGC-27, MKN-45, and GES-1 (adjusted p = 3.04 × 10⁻¹⁰, GSVA scores =0.71, 0.69, and 0.57, respectively). Additionally, the analysis identified candidate master regulators that may govern the activation of these biological programs.
Conclusion: Overall, our pathway-based classification might provide useful insights into molecular heterogeneity among GC cell lines which may facilitate the selection of appropriate cellular models for future studies.
Materials and Methods: To this end, we integrated our bulk RNA-seq raw count data from three HGC-27 GC cell line replicates with transcriptomic data from 18 independent public studies. The resulting dataset comprised 42 RNA-seq profiles, including 39 profiles from eight GC cell lines (HGC-27, MKN-45, KATO III, SNU-16, AGS, SNU-601, MKN-7, and FU97) and three profiles from the normal gastric cell line GES-1. CenTFinder was then used to identify active co-expression modules, followed by pathway, GO enrichment, and RcisTarget analyses to characterize biological functions and potential master regulators.
Results: We identified 14 co-expression modules. FU97, a gastric hepatoid adenocarcinoma cell line, showed enrichment of liver-associated metabolic processes, including “very-low-density lipoprotein particle remodeling” (Fisher’s exact test = 9.6 × 10⁻⁵), supporting the biological relevance of the identified modules (GSVA score = 0.89). Distinct module activity patterns were observed across cell lines, including significant enrichment of the “hsa00190-Oxidative Phosphorylation” pathway in HGC-27, MKN-45, and GES-1 (adjusted p = 3.04 × 10⁻¹⁰, GSVA scores =0.71, 0.69, and 0.57, respectively). Additionally, the analysis identified candidate master regulators that may govern the activation of these biological programs.
Conclusion: Overall, our pathway-based classification might provide useful insights into molecular heterogeneity among GC cell lines which may facilitate the selection of appropriate cellular models for future studies.
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