Identification of RFX5 as prognostic biomarker and associated with immune infiltration in stomach adenocarcinoma

Background: Regulatory factor X (RFX) gene family is a series of encodes transcription factors with a highly conserved DNA binding domain. RFXs played a vital role in the development and progression of cancer. However, the significance of RFXs in stomach adenocarcinoma (STAD) has not been fully clarified.

Methods: Online bioinformatics tools such as GSCALite, Kaplan-Meier Plotter, TIMER, LinkedOmics were used to explore the immunomodulatory function and clinical value of RFXs in STAD.

Results: The mRNA level of RFX1, RFX3, RFX4, RFX5, RFX7 and RFX8 was significantly elevated in STAD tissue versus adjacent normal tissue. We also summarize the copy number variation, single nucleotide variants and drug sensitivity of RFXs in STAD. Prognostic analysis indicated that STAD patients with high RFX5 and RFX7 expression had a better overall survival, first progression, and post-progression survival. Moreover, RFX5 expression was significantly associated with the abundance of immune cells, the expression of immune biomarkers and tumor mutational burden score in STAD. Functional enrichment analysis revealed that RFX5 and its related genes were mainly involved in T cell activation, antigen receptor-mediated signaling pathway, cell adhesion molecules, and Th17 cell differentiation. Validation study further verified the expression and prognosis of RFX5 in STAD. Further univariate and multivariate analyses suggested that pathological stage and RFX5 could be a potential independent prognostic factor for STAD.

Conclusions: RFX5 was a candidate prognostic biomarker and associated with immune infiltration in STAD.