FN1 overexpression is correlated with unfavorable prognosis and immune infiltrates in breast cancer.

ABSTRACT

Objective: To investigate the correlation of fibronectin 1 (FN1) expression with prognosis and tumor-infiltrating immune cells in breast cancer (BRCA). Methods: FN1 mRNA and protein expressions were analyzed through Tumor Immune Estimation Resource (TIMER), Gene Set Cancer Analysis (GSCA), Human Protein Atlas (HPA) databases, and immunohistochemical analysis. The clinicopathological characteristics and genetic factors affecting the FN1 mRNA expression were assessed by various public databases. Then, we analyzed the prognostic value of FN1 in BRCA by Kaplan-Meier plotter, receiver operating characteristic, and Cox regression analyses. Further, the UCSC Xena database was used to retrieve TCGA-BRCA expression profiles for functional enrichment analysis and immune cell infiltration analysis. The potential drugs for the BRCA patients with high- FN1 expression were identified using the connectivity map analysis. Results: FN1 was upregulated in BRCA tissues compared with normal tissues. High FN1 mRNA expression was correlated with poor clinical outcomes and had good performance in predicting the survival status of BRCA patients. Further, Cox regression analysis showed that FN1 was an independent prognostic factor for predicting the overall survival of patients with BRCA. Moreover, hypermethylation of FN1 contributed to a better prognosis for BRCA patients. Functional enrichment analyses revealed the ECM-receptor interaction pathway and focal adhesion as the common pathways. Moreover, FN1 showed a significant association with tumor-infiltrating immune cells and immune checkpoint inhibitors. Several drugs such as telmisartan, malotilate, and seocalcitol may have therapeutic effects in BRCA patients with high FN1 expression. Conclusion: FN1 might serve as a novel prognostic biomarker and a novel therapeutic target for BRCA. Besides, the association of FN1 with immune cells and immune checkpoint inhibitors may provide assistance for BRCA treatment.