ArticleFrontiers in genetics2025
Analysis of the correlation between RFC4 expression and tumor immune microenvironment and prognosis in patients with cervical cancer.
Article in Frontiers in genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Identification of replication factor C subunit 4 as a potential therapeutic target in esophageal squamous cell carcinoma based on bioinformatic analysis and machine learning.Discover oncology · 2026Article
- Deciphering the Role of Mast Cells in HPV-Related Cancers.International journal of molecular sciences · 2025Review
- Multiple roles of replication factor C family in pan‑cancer (Review).Oncology reports · 2025Review
- Association and interaction network analysis of immune cell subgroups in cervical cancer microenvironment based on Mendelian randomization.Discover oncology · 2025Article
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Authors and funding
5 authors.
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Abstract
Background: Replication factor C subunit 4 (RFC4) plays a critical role in the initiation and progression of some cancers; however, its relationship with tumor-infiltrating immune cells in cervical cancer (CC) has not been comprehensively analyzed. This study aimed to determine whether RFC4 overexpression affects overall survival in CC and to explore its impact and potential mechanisms on the tumor immune microenvironment. Methods: Data from Genotype-Tissue Expression database (GTEx) and Cancer Genome Atlas (TCGA) database were used as the exploration set. Datasets from the Gene Expression Omnibus (GEO) were used as the validation set. We also validated the expression of the RFC4 protein in the Human Protein Atlas (HPA) database and a real cohort. Clinical data on CC were evaluated for their association with RFC4 using TCGA and GEO databases. Possible relationships amongst RFC4, immune cells, and related genes were investigated using Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression (ESTIMATE). GO and KEGG pathway enrichment analyses were used to explore potential mechanisms. Tumor immune dysfunction and exclusion (TIDE) scores were used to predict the immunotherapeutic response to RFC4. Results: In the exploration, validation, and real cohort datasets, RFC4 expression was significantly elevated in CC tissues compared to that in normal tissues. Survival analysis based on TCGA and GEO datasets showed that CC patients with high RFC4 expression had a better prognosis than those with low expression. RFC4 expression was strongly correlated with some immunostimulators and immunoinhibitors. RFC4 expression was significantly negatively correlated with activated mast cell immune infiltration, activated CD4 memory T cells, M0 macrophages, and resting natural killer (NK) cells and significantly positively associated with activated dendritic cells, resting dendritic cells, and plasma cells. Conclusion: RFC4 is highly expressed in CC tissues. However, patients with high RFC4 expression in CC have a better prognosis, possibly because RFC4 exerts antitumor effects by affecting the immunostimulatory tumor microenvironment, such as immunostimulatory and dendritic cell infiltration.
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