Comprehensive analysis the diagnosis, malignant progression and immune infiltrate of ANXA6 in prostate cancer

Background: Annexins (ANXAs) play a crucial role in the development and progression of tumors. However, their specific involvement in prostate cancer (PCa) remains unclear.

Objective: To investigate the function and clinical significance of key ANXAs in PCa.

Methods: Multiple databases were used to analyze the expression levels, genetic variations, potential prognostic value and clinical significance of ANXAs in PCa. Then, the co-expressed genes of ANXA6 were identified, and the correlation between ANXA6 and immune cell infiltration was validated using the Tumor Immune Estimation Resource (TIMER) database. Additionally, in vitro assays such as Cell Counting Kit-8 (CCK-8), Colony Formation, Transwell and T-cell Chemotaxis assays were conducted to validate the functions of ANXA6. Moreover, multiple types of in vivo assays were performed to further validate the identified ANXA6 functions.

Results: The results demonstrated that ANXA2, ANXA6 and ANXA8 were significantly downregulated in PCa. ANXA6 upregulation was significantly associated with improved PCa patients' overall survival. Enrichment analysis revealed that ANXA6 and its co-expressed genes were involved in tumor progression, and ANXA6 overexpression could effectively inhibit the proliferation, migration and invasion of PC-3 cells. In vivo studies also demonstrated that ANXA6 overexpression suppressed tumor growth. Importantly, ANXA6 was found to promote the chemotaxis of CD4⁺ T cells and CD8⁺ T cells towards PC-3 cells, and the overexpression of ANXA6 in PC-3 cells promoted the polarization of macrophages into M1 macrophages in the supernatant of PCa cells.

Conclusions: ANXA6 demonstrated promising potential for consideration as a prognostic biomarker in PCa as it was found to play key roles in regulating immune cell infiltration and the malignant progression to PCa.