Abstract
BackgroundCardiotrophin-like cytokine factor 1 (CLCF1) has been described as an oncogene and a potential therapeutic target in a variety of cancers, but its role in glioma remains unknown.MethodsBased on The Cancer Genome Atlas (TCGA), we conducted a bioinformatics analysis to investigate the clinical significance and biological functions of CLCF1 in glioma at the transcriptional level and predicted the response to immunotherapy of glioma patients with different CLCF1 expression levels. All the results were further verified in Chinese Glioma Genome Altas(CGGA) Data processing and figure generating were performed with R language.ResultsElevated CLCF1 expression was common in cancers and usually predicted poor prognosis, which was also consistent with gliomas. In Univariate Cox Regression analysis and Kaplan-Meier survival analysis, tumor patients with higher CLCF1 expression tended to experience a worse prognosis. In the multivariate Cox proportional hazard model, the expression of CLCF1 was an independent prognostic factor in gliomas. The biological function analysis of CLCF1 in glioma showed that CLCF1 was closely associated with immune signatures, including immune-related pathways, immune cell infiltration, and immune checkpoints. Moreover, glioma patients with low CLCF1 expression showed a greater tendency to respond to anti-PD1/PD-L1 immunotherapy, indicating CLCF1 also had potential clinical significance in guiding immunotherapy. And CLCF1 as a member of the IL6 family had a better predictive value for prognosis and immunotherapy response in glioma than that of IL6 and other IL6 family members.ConclusionCLCF1 expression is an independent prognosticator and a promising therapeutic target correlated with immunotherapy in glioma.
Highlights
Gliomas are the most common and lethal malignant central nervous tumors, the therapeutic effects of currently available conventional treatment including surgical resection, chemotherapy, and radiotherapy are limited [1, 2]
Elevated Cardiotrophin-like cytokine factor 1 (CLCF1) expression was common in cancers and usually predicted poor prognosis, which was consistent with gliomas
The biological function analysis of CLCF1 in glioma showed that CLCF1 was closely associated with immune signatures, including immune-related pathways, immune cell infiltration, and immune checkpoints
Summary
Gliomas are the most common and lethal malignant central nervous tumors, the therapeutic effects of currently available conventional treatment including surgical resection, chemotherapy, and radiotherapy are limited [1, 2]. The dysregulation of IL-6 family cytokine expression and the corresponding receptor signaling pathways is a common phenomenon in cancers and is often associated with adverse clinical outcomes [15]. The known role of CLCF1 in tumors is mainly related to the immune microenvironment. As an IL-6 family cytokine with the neurodevelopmental function that participates in the regulation of the tumor immune microenvironment, CLCF1 has been found to be a promising prognostic marker and target associated with PTEN mutation in glioma in a recent study [21], but its specific role remains to be further explored. Cardiotrophin-like cytokine factor 1 (CLCF1) has been described as an oncogene and a potential therapeutic target in a variety of cancers, but its role in glioma remains unknown
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