Research Paper Volume 13, Issue 17 pp 21758—21777

The upregulated expression of RFC4 and GMPS mediated by DNA copy number alteration is associated with the early diagnosis and immune escape of ESCC based on a bioinformatic analysis

Jing Wang1, *, , Fei-Fei Luo1, *, , Tie-Jun Huang3, , Yan Mei1, , Li-Xia Peng1, , Chao-Nan Qian1,2, , Bi-Jun Huang1, ,

  • 1 Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People’s Republic of China
  • 2 Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People’s Republic of China
  • 3 Department of Nuclear Medicine, The Second People’s Hospital of Shenzhen, Shenzhen 518037, People’s Republic of China
* Equal contribution

Received: April 12, 2021       Accepted: August 31, 2021       Published: September 14, 2021
How to Cite

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Esophageal squamous cell carcinoma (ESCC) is a malignant tumor that commonly occurs worldwide. Usually, Asia, especially China, has a high incidence of esophageal cancer. ESCC often has a poor outcome because of a late diagnosis and lack of effective treatments.

To build foundations for the early diagnosis and treatment of ESCC, we used the gene expression datasets GSE20347 and GSE17351 from the GEO database and a private dataset to uncover differentially expressed genes (DEGs) and key genes in ESCC. Notably, we found that replication factor C subunit 4 (RFC4) and guanine monophosphate synthase (GMPS) were upregulated but have been rarely studied in ESCC. In particular, to the best of our knowledge, our study is the first to explore GMPS and ESCC. Furthermore, we found that high levels of RFC4 and GMPS expression may result from an increase in DNA copy number alterations. Furthermore, RFC4 and GMPS were both upregulated in the early stage and early nodal metastases of esophageal carcinoma. The expression of RFC4 was strongly correlated with GMPS. In addition, we explored the relationship between RFC4 and GMPS expression and tumor-infiltrating immune cells (TILs) in esophageal carcinoma. The results showed that the levels of RFC4 and GMPS increased with a decrease in some tumor-infiltrating cells. Upregulated RFC4 and GMPS with high TILs indicate a worse prognosis.

In summary, our study shows that RFC4 and GMPS have potential as biomarkers for the early diagnosis of ESCC and may played a crucial role in the process of tumor immunity in ESCC.


EA: esophageal adenocarcinoma; ESCC: esophageal squamous cell carcinoma; DEGs: differentially expressed genes; RFC4: replication factor C subunit 4; GMPS: guanine monophosphate synthase; GEO: The Gene Expression Omnibus database; TCGA: The Cancer Genome Atlas; GO: Gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; PPI: protein-protein interaction; GSEA: Gene set enrichment analysis; TILs: Tumor-infiltrating immune cell.