Identification ATP5F1D as a Biomarker Linked to Diagnosis, Prognosis, and Immune Infiltration in Endometrial Cancer Based on Data-Independent Acquisition (DIA) Analysis.

Abstract

In developed countries, endometrial cancer (EC) is the most prevalent gynecological cancer. ATP5F1D is a subunit of ATP synthase, as well as an important component of the mitochondrial electron transport chain (ETC). ETC plays a compelling role in carcinogenesis. To date, little is known about the role of ATP5F1D in EC. We undertook data-independent acquisition mass spectrometry (DIA-MS) of 20 EC patients, comprising 10 high-grade and 10 low-grade cancer tissues. Biological functions of differentially expressed genes (DEGs) were analyzed by GO and KEGG. The expression level, clinicopathological features, diagnostic potency, prognostic value, RNA modifications, immune characteristics, and therapy response of ATP5F1D were investigated. In total, 77 DEGs were acquired by DIA analysis, which were closely related to regulating immune response and metabolic pathways. Among the five genes (NDUFB8, SLC26A2, RAF1, ATP5F1D, and GSTM5) involving in reactive oxygen species pathway, ATP5F1D showed the most significant differential expression (2.903-fold change). We found ATP5F1D had a high diagnostic value and was associated with a favorable prognosis in EC patients. After analyzing the RNA modifications of ATP5F1D, revealing a negative regulation between them. Additionally, ATP5F1D was closely related to tumor immune infiltration. Our results suggested T-cell dysfunction and TAM-M2 polarization might be the important mechanisms of ATP5F1D to facilitate tumor immune escape. Noticeably, EC patients with ATP5F1D-high expression had better immune treatment responses and were more sensitive to chemotherapy drugs. ATP5F1D can be used as a biomarker for diagnosis, prognosis, and immune infiltration of EC, and offers a crucial reference for personalized treatment of EC patients.