Purpose:
Our objective is to explore potential biomarkers of renal cancer and their function in tumor progession.
Methods:
We integrated data from the TCGA database, including Kidney Chromophobe(KICH), Kidney renal papillary cell carcinoma(KIRP), and Kidney renal clear cell carcinoma(KIRC), to identify the widespread differentially expressed genes. Molecular Complex Detection (MCODE) was then utilized to screen the most important module among the upregulated genes. Further, univariate and multivariate Cox regression analyses were performed on the hub genes. The results demonstrated that Centromere Protein F(CENPF) overexpression was significantly associated with a worse survival in KIRC patients. To validate the overexpression of CENPF, we conducted qPCR analysis on tissues and plasma samples from KIRC patients. we observedthat patients with high expression of CENPF had a poorer prognosis based on KIRC TCGA data. Through single-cell sequencing analysis of KIRC patients in GSE159115, we found that CENPF is predominantly expressed in the T cell cluster. Finally, we used CIBERSORT to analyze the differences in composition of tumor immune infiltrating cell (TIIC) between KIRC patients exhibiting high and low expression of CENPF.
Results:
1. We screen out CENPA, Centromere Protein M(CENPM), Centromere Protein U(CENPU), Centromere Protein E(CENPE), and CENPF as key oncogenic genes upregulated in KIRC, KICH, and KIRP.
2. We found that CENPF expression was significantly associated with KIRC progression.
3. We observed a T-cell sub-cluster that exhibited high expression of CENPF.
4. CENPF displayed a significant negative correlation with resting mast cells, while it exhibited a positive correlation with follicular helper T-cells and memory-activated CD4 T-cells.
5. Prognostic analysis revealed that patients with high expression of follicular helper T-cells had poorer prognosis, while those with high expression of plasma cells had a better prognosis.
Conclusion:
CENPF is upregulated and modulates the immune microenvironment in KIRC.