Ovarian cancer is one of the most common gynaecological cancers affecting more than 300,000 women worldwide each year. S100 calcium-binding protein A6 (S100A6) is a member of the S100 family of calcium-binding proteins. Upon activation by calcium (Ca²⁺) signalling, S100A6 regulates numerous cellular processes including cell proliferation and metastasis. The role of S100A6 is well established across multiple tumour types where increased S100A6 expression contributes to tumourigenesis and worse patient outcome. However, the role of S100A6 in ovarian cancer is not well established.

The impact of cytoplasmic and nuclear S100A6 expression on overall survival and clinicopathological criteria was investigated in 462 ovarian tumours by immunohistochemistry. Additionally, S100A6 expression in an ovarian cancer cohort from The Cancer Genome Atlas (TCGA) PanCancer dataset (n = 299) was evaluated and associations with overall survival and progression-free survival were identified.

Immunohistochemical staining revealed that high cytoplasmic expression of S100A6 was significantly associated with better overall survival (p = 0.014). Additionally, high nuclear expression was significantly associated with better overall survival (p = 0.036). In contrast, analysis of mRNA S100A6 suggests no significant association of mRNA levels for overall survival (p = 0.903) and progression free survival (p = 0.278).

Our data provides novel insights regarding the clinical implications of S100A6 expression in ovarian cancer, providing strong rationale for functional investigations of S100A6 in ovarian cancer.