Deciphering the Multifaceted Role of EXO1 in Female-Related Cancers: Implications for Prognosis and Therapeutic Responsiveness

Cong YuGuoying Wu^*

• School of Life Science, Qilu Normal University, Jinan, China

Aberrant function or overactivation of exonuclease 1 (EXO1) may be associated with cancer tumor development, drug resistance and response to immunotherapy in female-related cancers. By analyzing RNA-sequencing data from The Cancer Genome Atlas database, combined with validation through quantitative polymerase chain reaction experiments, we explored the expression levels of EXO1 in breast cancer (BRCA) cell lines and assessed its multidimensional roles in BRCA, cervical cancer, ovarian cancer, thyroid cancer, uterine corpus endometrial cancer, and uterine sarcoma. Our quantitative polymerase chain reaction experiments revealed elevated expression of EXO1 in BRCA cell lines, consistent with the RNA-sequencing data from The Cancer Genome Atlas database, confirming the upregulation of EXO1 in BRCA. The high expression of EXO1 is associated with poor prognosis in various female-related cancers, particularly in BRCA and uterine sarcoma. The expression levels of EXO1 significantly correlate with clinical and pathological characteristics, including ethnicity, age, pathological staging, and treatment modalities. In specific cancer subtypes, such as the basal-like subtype of BRCA, high EXO1 expression is associated with a better prognosis, potentially related to enhanced DNA repair capabilities. Genetic mutation analysis indicates a higher frequency of EXO1 gene mutations in uterine sarcoma and BRCA; however, the impact on prognosis may vary across different cancers. DNA methylation levels may play a role in the regulation of EXO1 gene expression in BRCA, uterine corpus endometrial cancer, and thyroid cancer, but are not significantly correlated with prognosis. EXO1 expression is correlated with various factors within the tumor immune microenvironment, including immune cell infiltration and the expression of immune molecules, particularly showing a positive correlation with the infiltration of T helper 2 cells and helper T cells. Furthermore, EXO1 may be associated with the sensitivity to anticancer drugs. In summary, EXO1 exhibits multidimensional roles in female-related cancers, serving as a prognostic biomarker, and potentially influencing tumor immune therapy responses and drug sensitivities.