Clinical Significance of Fragile X Syndrome 2 (FXR2) in Breast Cancer

<b>Background</b>: The fragile X protein family comprises three members: the fragile X syndrome protein (FMRP) and its structural homologs, fragile X syndrome 1 and 2 (FXR1 and FXR2). FMRP has a significant role in controlling the genesis and progression of various forms of human cancer. However, studies on the prognostic significance of FXR2 in cancer are scarce. Thus, this study aimed to investigate the clinicopathological significance of FXR2, a member of the FMRP family, in primary breast cancer (BC). <b>Methods</b>: A total of 100 formalin-fixed paraffin-embedded (FFPE) tissue blocks from invasive BC cases were collected from King Abdulaziz Hospital in Saudi Arabia. Immunohistochemistry (IHC) was used to assess FXR2 protein expression in the BC tissues, and the results were correlated with clinicopathological parameters, such as tumor grade, tumor size and hormone receptor status. Additionally, the association between clinicopathological features and <i>FXR2</i> mRNA expression was assessed using the BC Gene-Expression Miner v5.0 tool on all publicly available DNA microarray (<i>n</i> = 10,872) and RNA sequence (<i>n</i> = 4421) data to validate the results. <b>Results</b>: FXR2 protein expression was significantly associated with human epidermal growth factor 2 (HER2) negativity (<i>p</i> = 0.010) and low Ki67 (<i>p</i> < 0.001). Both DNA microarray and RNA sequence data showed that HER2 negativity was strongly linked to high levels of <i>FXR2</i> mRNA. High <i>FXR2</i> mRNA levels were also correlated with hormone receptor negativity and mutated p53. <b>Conclusions</b>: This study suggests that FXR2 may have indirect clinical significance in BC. However, further studies are warranted to deepen our understanding of the association between FXR2 and other clinicopathological parameters, which could lead to improved diagnostic, treatment, and prognostic strategies for BC patients.