Mingjing Meng ^1* Jiani Wang ² Jiumei Yang ³ Yangming Zhang ⁴ Xusheng Tu ⁵ Pan Hu ²

• ¹ Department of Research and Foreign Affairs, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China, Zhengzhou, China
• ² Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China, Guangzhou, China
• ³ Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510000, China, Guangzhou, China
• ⁴ Equipment Department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China, Guangzhou, China
• ⁵ Emergency department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China, Guangzhou, China

Breast cancer continues to be a primary cause of cancer-related mortality among women globally. Identifying novel biomarkers is essential for enhancing patient prognosis and informing therapeutic decisions. The PRR13 gene, associated with taxol resistance and the progression of various cancers, remains under-characterized in breast cancer. This study aimed to investigate the role of PRR13 in breast cancer and its potential as a prognostic biomarker. We performed a comparative analysis of PRR13 gene expression utilizing the TCGA database against non-cancerous tissues and employed STRING to evaluate PRR13's protein-protein interactions and associated pathways. Additionally, we investigated the relationship between PRR13 mRNA expression and immune cell infiltration in breast cancer (BRCA) using two methodologies. Furthermore, a retrospective analysis of 160 patients was conducted, wherein clinical data were collected and PRR13 expression was evaluated through immunohistochemistry and qRT-PCR to determine its association with clinicopathological features and patient survival. Analysis of the TCGA database revealed significant upregulation of PRR13 expression across 12 different cancer types, including breast cancer. High PRR13 expression was positively correlated with various immune cells, including NK cells, eosinophils, Th17 cells, and mast cells, whereas a negative correlation was observed with B cells, macrophages, and other immune subsets. Enrichment analysis of PRR13 and its 50 interacting proteins revealed significant associations with biological processes such as cell adhesion and migration, and pathways including ECM-receptor interaction and PI3K-Akt signaling. Single-cell analysis demonstrated associations between PRR13 and pathways pertinent to inflammation and apoptosis. Validation studies confirmed elevated PRR13 expression in tumor tissue compared to adjacent non-cancerous tissue. Immunohistochemistry demonstrated high PRR13 expression in 55.6% of cancer cases, particularly associated with advanced clinical stage and lymph node metastasis. Moreover, high PRR13 expression significantly correlated with shorter overall survival and served as an independent prognostic factor. Subgroup analysis underscored the prognostic significance of PRR13 in aggressive tumor subtypes, with particularly strong associations observed in T3, N1-3, and moderately to poorly differentiated tumors. In conclusion, PRR13 expression is upregulated in breast cancer tissues and may serve as a valuable prognostic indicator for breast cancer patients, potentially impacting patient survival and therapeutic strategies.