SLC8A1, a novel prognostic biomarker and immunotherapy target in RSA and UCEC based on scRNA-seq and pan-cancer analysis

Abstract

Purpose As the field of gynecological immunology increasingly focuses on reproduction, the importance of recurrent spontaneous abortion (RSA) is growing. The complex mechanisms underlying the interaction between RSA and cancer are still not well understood. This study seeks to identify a new prognostic biomarker for RSA and cancer. Methods Weighted Gene Co-Expression Network Analysis (WGCNA), single-cell RNA sequencing (scRNA-seq), and machine learning algorithms were utilized for the analysis of RSA decidua samples (GSE164449, GSE214607, GSE65099) to identify the hub gene. The expression and distribution of the hub gene were subsequently investigated using the pan-cancer database TCGA. Furthermore, a prognostic prediction was made to assess the hub gene's impact on cancer response, mutation burden, immunity microenvironment, immune checkpoint, and chemotherapy. Results SLC8A1 has been identified as a hub gene within the RAS. In pan-cancer analysis, SLC8A1 exhibited strong expression levels in UCEC. The efficacy of SLC8A1 as a predictive marker was substantiated by calibration curves and concordance index. The mutation rate of SLC8A1 was found to be 6% based on the waterfall plot. Immune analysis revealed notable differences in the fractions of T cells and macrophages between the high and low expression groups. The analysis of immune checkpoint has demonstrated notable associations with CD40positive immune checkpoints. Notably, patients classified in the low-risk group exhibited enhanced responsiveness to Osimertinib, Dasatinib, Sepantronium bromid, lbrutinib, and other treatments. Conclusion These findings suggest that SLC8A1 may serve as a promising prognostic biomarker and potential target for immunotherapy in the context of RSA and UCEC.