Abstract
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.
Highlights
Diffuse lower-grade gliomas (LGG) represent the highly heterogeneous and infiltrative neoplasms in the central nervous system (CNS)
The results showed that Replication factor C 2 (RFC2) was generally highly expressed in many types of cancer tissues compared with normal tissues, including brain and CNS cancer, colorectal cancer, gastric cancer, head and neck cancer, kidney cancer, myeloma, ovarian cancer, sarcoma, and other cancer (Fig. 1A)
Previous limited studies hinted that RFC2 exerted a potential carcinogenic role in several cancer types, including colorectal cancer (CRC)18, HCC19, and ESCC24
Summary
Diffuse lower-grade gliomas (LGG) represent the highly heterogeneous and infiltrative neoplasms in the central nervous system (CNS). The immune checkpoint blockade (ICB) therapies, including cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors, as well as chimeric antigen receptor (CAR) T cells have been widely approved for clinical use in many types of cancer, such as melanoma, non-small cell lung cancer (NSCLC), classical Hodgkin Lymphoma, and urothelial bladder cancer, and revealed a robust anti-tumor effect in these malignancies[8,9]. These representative immune therapies show less favorable efficacy in LGG, as it hijacks immune checkpoints to escape immune surveillance through its harsh tumor microenvironment (TME)[10]. The functional roles of RFC2 in the regulation of progression and TME in LGG have not been fully elucidated
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