| Summary: | Signet-ring cell carcinoma (SRC) in advanced gastric cancer (GC) is often associated with more invasiveness and a worse prognosis than other cell types. The genetic alterations associated with gastric carcinogenesis in SRC are still unclear. In this study, 441 GC patients receiving curative surgery for GC between 2005 and 2013 were enrolled. The clinicopathological characteristics and genetic alterations of GC patients with and without SRC were compared. Among the 441 GC patients, 181 had SRC. For early GC, patients with SRC had more tumors located in the middle and lower stomach, more infiltrating tumors and better overall survival (OS) rates than those without SRC. For advanced GC, patients with SRC had more scirrhous type tumors, more <i>PIK3CA</i> amplifications, fewer microsatellite instability-high (MSI-H) tumors, more peritoneal recurrences and worse 5-year OS rates than those without SRC. For advanced GC with SRC, patients with peritoneal recurrence tended to have <i>PD-L1</i> expression. For advanced GC without SRC, patients with liver metastasis tended to have <i>PD-L1</i> expression, <i>PI3K/AKT</i> pathway mutations, <i>TP53</i> mutations and MSI-H tumors. For advanced GC, <i>PD-L1</i> expression was associated with peritoneal recurrence in SRC tumors, while non-SRC tumors with liver metastasis were likely to have <i>PI3K/AKT</i> pathway mutations, <i>TP53</i> mutations and <i>PD-L1</i> expression; immunotherapy and targeted therapy may be beneficial for these patients.
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