FBLN5 Is an Underlying Common Tumor Suppressor in Breast Cancer and Thyroid Cancer

Background: Breast cancer (BC) patients have a greater risk of developing thyroid cancer (TC) than the general population. Similarly, TC patients are more likely to develop BC, suggesting an underlying common etiology. In this study, we sought to identify the potential cross-talking pathway and related molecular mechanisms conferring to the sequential development of BC and TC.Methods: We first used Multiple Primary-Standardized Incidence Ratios (MP-SIR) Program of SEER*Stat to calculate SIR to confirm the relationship between BC and TC. Then the RNA-seq was downloaded from The Cancer Genome Atlas (TCGA). And we built a co-expression network via Weighted Gene Co-expression Network Analysis (WGCNA) and obtained the most significant modules. The key genes were obtained by differential gene expression (DGE) analysis and WGCNA analysis. Furthermore, String database and Cytoscape software were used to construct protein-protein interactions (PPI), and defined the maximum Maximal Clique Centrality (MCC) value as hub gene.Then we performed prognosis analysis on the hub genes and obtained the prognostic genes of BC and TC. Finally, gene set enrichment analysis (GSEA) was used to investigate the molecular pathways associated with prognostic gene expressed both in BC and TC.Results: From the SEER database, we found that the risk of developing BC in TC patients was SIR 1.12, 95% CI [1.07, 1.18], and the risk of developing BC in TC patients was SIR 1.29, 95% CI [1.23, 1.26]. Fifty-nine key genes obtained by differential expression analysis and WGCNA identify that PI3K/AKT was the most enriched pathway in BC and TC. In addition, the Recombinant Fibulin 5 (FBLN5) was shown to be of significant prognostic value for both BC and TC and was down-regulated in BC and TC tissues. GSEA demonstrated that FBLN5 enrichment pathways associated with BC and TC mainly included: B cell receptor signaling pathway, steroid hormone biosynthesis, and pathways in cancer.Conclusions: The PI3K/AKT signaling is most co-enriched pathway in BC and TC. FBLN5 is the most relevant prognostic gene and an underlying common tumor suppressor in both BC and TC, with down-stream pathways involving immunity, hormone biosynthesis and carcinogenesis.