Prognostic Role of Receptor Tyrosine Kinase–Like Orphan Receptors in Intestinal-Type Gastric Cancer

Abstract

Background:Gastric cancer (GC) is diagnosed at advanced stages and has high mortality rates. Surgical resection and adjuvant chemotherapy are the main therapeutic approaches for GC. Despite curative resection, recurrence and metastasis contribute to a high mortality rate in patients with GC. The receptor-tyrosine-kinase-like orphan receptors 1/2 (ROR1/2) are transmembrane proteins belonging to the receptor tyrosine kinase (RTK) family. ROR1 and ROR2 are known to overexpress in the tumor tissues from several types of cancer patients. However, the role of RORs in the prognosis has not been understood. Methods:This study aimed to determine the association of mRNA expression of ROR1, ROR2, and their signaling components WNT5A, NKX2-1, and FOXF1, with the survival outcome of GC patients. We performed Kaplan-Meir survival analysis on publicly available ‘The Cancer Genome Atlas (TCGA)’ data sets using ‘Kaplan-Meir Plotter.’ Results:High mRNA expression of ROR1, ROR2, NKX2-1, and FOXF1 was significantly correlated with worse overall survival (OS) of GC patients. Interestingly ROR1 and ROR showed a prognostic role in the intestinal subtype, but not in the diffuse subtype of GC. Furthermore, ROR1 was positively correlated with regulatory T cells and M2-type macrophages and negatively correlated with Th17 and natural killer T cells in the tumor stroma of patients with GC. Conclusion:We conclude that the expression of ROR1, ROR2, and their associated genes correlate with worst prognosis of GC patients, particularly in the intestinal type.