Abstract 258: Identification of characteristic genes of scirrhous-type gastric cancer cells by RNAseq
Authors: Sera Tomohiro , Yashiro Masakazu , Tsujio Gen , Yamamoto Yurie , Sugimoto Atsushi , Kushiyama Shuhei , Nishimura Sadaaki , Ohira Masaichi 
Published: July 2021

Introduction: Scirrhous gastric cancer shows an extremely poor prognosis with rapid growth and infiltration activity. One of the reasons for poor prognosis is a lack of the identification of driver gene for scirrhous gastric cancer. FGFR2 (fibroblast growth factor receptor 2), E-cadherin, TGFβR (transforming growth factor β receptor), CD44/IGFIR (insulin-like growth factor I receptor), have been reported as candidates of driver for scirrhous-type of gastric cancer, however useful molecular-targeted therapeutic agents against these driver molecules have not yet been clinically approved. In this study, we identified the characteristic genes of scirrhous-type gastric cancer by RNA-seq of gastric cancer cell lines.

Methods: RNA-seq was performed using 6 scirrhous gastric cancer cell lines (OCUM1, OCUM2MLN, OCUM8, OCUM12, OCUM13, OCUM14) using a next-generation sequencer (ION S5 system, Thermo Fisher Scientific). Furthermore, RNA-seq public data of 4 strains of scirrhous gastric cancer cell lines (KATO3, NUGC4, SNU601, SNU668) and 10 strains of non-scirrhous gastric cancer cell lines (MKN7, MKN45, MKN74, HS746T, SNU1, SNU16, SNU638, AZ521, HGC27, TMK1) on the Sequence Read Archive were added, and the genes expressed in scirrhous gastric cancer were compared and examined. The analysis tools used were kallisto and sleuth. We set p-value &lt; 0.05 and log2 (fold change) &gt; 2 as the cut-offs to screen out differentially expressed genes (DEGs). Pathway enrichment and protein-protein interaction (PPI) network analysis were performed based on metascape databases. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was also performed for the genes.

Results: A total of 234 DEGs were identified from this analysis. A gene co-expression network was constructed containing 8 DEGs. The genes were mainly associated with response to chemokine, and cytokine-mediated signaling pathway. Several critical genes were disclosed, such as C-C motif chemokine ligand 20 (CCL20) and C-X-C subfamiliy. Genes highly expressed in scirrhous gastric cancer cell lines were CCL20 (10.6-fold change, p=9.89×10-4) and C-X-C Motif Chemokine Ligand 3 (CXCL3, 19.5-fold change, p=1.67×10-5). The mean of abundances across samples (=log(counts+0.5)), which represent the average expression levels of all samples, were CCL20 and CXCL3, 4.04 and 4.53, respectively. KEGG pathway enrichment analysis showed that viral protein interaction with cytokine and cytokine receptor, Cytokine-cytokine receptor interaction and IL-17 signaling pathway were significantly over-represented.

Conclusion: CCL20 and CXCL3 might be characteristic genes for scirrhous-type of gastric cancer.

Citation Format: Tomohiro Sera, Masakazu Yashiro, Gen Tsujio, Yurie Yamamoto, Atsushi Sugimoto, Shuhei Kushiyama, Sadaaki Nishimura, Masaichi Ohira. Identification of characteristic genes of scirrhous-type gastric cancer cells by RNAseq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 258.