RFC2: a prognosis biomarker correlated with the immune signature in diffuse lower-grade gliomas

• Published in: Scientific reports Vol. 12; no. 1; p. 3122
• Main Authors: Zhao, Xu, Wang, Yuzhu, Li, Jing, Qu, Fengyi, Fu, Xing, Liu, Siqi, Wang, Xuan, Xie, Yuchen, Zhang, Xiaozhi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 24.02.2022; Nature Publishing Group UK; Nature Portfolio
• Subjects: Biomarkers; Biomarkers, Tumor - genetics; Brain Neoplasms - pathology; Cancer; Central nervous system; China; Computational Biology; Databases, Genetic; DNA biosynthesis; DNA repair; Gene Expression - genetics; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic - genetics; Glioma; Glioma - immunology; Glioma - pathology; Humans; Immune checkpoint; Infiltration; Lymphocytes, Tumor-Infiltrating - immunology; Metastases; Microsatellite Instability; Mismatch repair; Prognosis; Replication factor C; Replication Protein C - genetics; Replication Protein C - metabolism; Transcriptome - genetics; Tumor microenvironment; Tumor Microenvironment - genetics; Tumors; China
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-06197-5

Diffuse lower-grade gliomas (LGG) represent the highly heterogeneous and infiltrative neoplasms in the central nervous system (CNS). Replication factor C 2 (RFC2) is a subunit of the RFC complex that modulates DNA replication and repair. However, the prognosis value of RFC2 and its association with the immune signature of tumor microenvironment (TME) in LGG remains unknown. Based on Oncomine, TCGA, GTEx, TIMER, GEPIA, and HPA databases, we evaluated RFC2 expression levels and its clinical prognostic value in LGG and other cancers. Then we analyzed the correlations between RFC2 expression and tumor mutation burden (TMB), tumor microsatellite instability (MSI), and mismatch repair (MMR) genes across cancers. And CIBERSORT and ESTIMATE algorithms were conducted to estimate the association of RFC2 with immune cell infiltration of LGG. Additionally, we performed the functional enrichment analyses of RFC2 in LGG. Then functional experiments were employed to further validate the oncogenic role of RFC2 in LGG. Our results showed that RFC2 was widely highly expressed in most types of cancer. And its expression was closely related to the clinicopathological features and prognosis in LGG and other cancer types. RFC2 levels were also correlated with TMB and MSI across various cancers. Furthermore, RFC2 was positively associated with the infiltration levels of immune cells and immune checkpoint genes in LGG. Additionally, in vitro experiments revealed that RFC2 played an oncogenic role in LGG progression. In conclusion, our findings revealed that RFC2 could serve as a reliable biomarker to predict the prognosis and immune signature for LGG.