Increased co-expression of MEST and BRCA1 is associated with worse prognosis and immune infiltration in ovarian cancer

Objective: The crosstalk between tumor microenvironment (TME) and cancer cells plays a critical role in the occurrence and development of ovarian cancer. Imprinted gene MEST is a tumor-promoting factor that modulates several carcinogenic signaling pathways. This study aimed to investigate the expression pattern of MEST and its association with immune cell infiltration.

Methods: The transcriptome data of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database was utilized, and the expression and immune characteristics of MEST were verified by immunohistochemistry of ovarian cancer specimens. Kaplan-Meier Plotter was used to assess the prognostic value in patients with ovarian cancer.

Results: We found that high expression of MEST was associated with diminished immune cell infiltration and worse prognosis of ovarian cancer patients in independent cohorts. There was a positive correlation between MEST and BRCA1 expression. The MEST^highBRCA1^high ovarian cancer group was correlated with lower infiltration of CD4⁺ cells, CD57⁺ cells, CD68⁺ cells and MPO⁺ cells, had worse overall survival (OS) in TCGA (HR = 1.57, p = 0.0004) and GSE27651 (HR = 4.27, p = 0.0002) cohorts, and predicted poor progress free survival (PFS) in GSE9891 (HR = 1.76, p = 0.0098) and GSE15622 (HR = 4.80, p = 0.0121) cohorts. Moreover, the expression of PD-L1 predicted unfavorable OS (HR = 2.48, p = 0.0415) and PFS (HR = 2.36, p = 0.0215) in MEST^lowBRCA1^low ovarian cancer group in GSE9891 cohort.

Conclusion: These findings suggest that the co-expression of MEST and BRCA1 may be an ideal combination for predicting the prognosis and response to immunotherapy in patients with ovarian cancer.