Comprehensive bioinformatics analysis of co-mutation of FLG2 and TP53 reveals prognostic effect and influences on the immune infiltration in ovarian serous cystadenocarcinoma.

Abstract

Background: Ovarian cancer remains one of the most lethal gynecological malignancies, characterized by late-stage diagnosis and high rates of recurrence. The present study aims to explore the prognostic and immunological implications of FLG2 and TP53, the two genes exhibiting a high mutation frequency across various cancer types, in the context of ovarian serous cystadenocarcinoma (OV).

Methods: The study systematically analyzed and discussed the potential implications of co-mutation of FLG2 and TP53 on prognosis and immune response using a cohort of 585 ovarian cancer samples. The differentially expressed genes (DEGs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on 300 ovarian cancer samples with RNA sequencing (RNA-seq) data.

Results: The co-mutation of FLG2 and TP53 was identified in the 585 ovarian cancer cohort, and the group with co-mutation exhibited improved outcomes in terms of overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). Additionally, the co-mutation (FLG2 ⁺/TP53 ⁺) group demonstrated higher scores in tumor mutation burden (TMB) comparing to that of the other three groups. The score of microsatellite instability (MSI) in the co-mutant group was only higher than that of the co-wild-type (FLG2 ^-/TP53 ^-). A total of 327 DEGs were identified in both the co-mutation and non-co-mutation (NCM) groups using limma analysis in the subgroup of 300 patients with RNA-seq data. Subsequent KEGG analysis revealed that these DEGs were implicated in various biological processes, including thermogenesis, Parkinson's disease (PD), and oxidative phosphorylation signaling pathways. Additionally, the co-mutation group exhibited elevated levels of various immune cells. Furthermore, a nomogram with high predictive accuracy was developed by integrating co-mutation status with clinical characteristics.

Conclusions: In the context of OV, the concurrent mutation of FLG2 and TP53 not only induces immune activation, but also helps identify a subset of patients with a more favorable prognosis.