Prognostic significance of CKAP2L expression in patients with clear cell renal cell carcinoma
Authors: Liu Zhi , Zhang Jun , Shen Deyun , Hu Xuechun , Ke Zongpan , Ehrich Lister I Nyoman , Sihombing Bungaran 
Published: January 2023

Background: Cytoskeleton-associated protein 2-like protein (CKAP2L) is thought to promote the progression of glioma, breast cancer, and ovarian cancer. However, the role of cytoskeleton-associated protein 2-like protein in clear cell renal cell carcinoma (ccRCC) is still unclear. The study aimed to investigate the roles and mechanisms of cytoskeleton-associated protein 2-like protein in clear cell renal cell carcinoma.

Methods: The level of cytoskeleton-associated protein 2-like protein in tumors was explored by using UALCAN and Oncomine databases. Gene expression datasets of clear cell renal cell carcinoma from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) were also used to validate the cytoskeleton-associated protein 2-like protein level in clear cell renal cell carcinoma. Survival analysis was performed to investigate the relationship between cytoskeleton-associated protein 2-like protein level and prognosis of clear cell renal cell carcinoma patients. Cox regression analysis was used for identifying the independent prognostic factors. Gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), protein–protein interaction analysis, co-expression analysis, and immune infiltration analysis were used to explore the potential mechanisms of cytoskeleton-associated protein 2-like protein in clear cell renal cell carcinoma. Moreover, the levels of cytoskeleton-associated protein 2-like protein in clinical clear cell renal cell carcinoma tissues were also measured using RT-PCR, immunohistochemical analysis, and Western blotting. M1 macrophages and CD4+ T cells were also detected by immunohistochemistry between tumor and normal tissues.

Results: The level of cytoskeleton-associated protein 2-like protein was upregulated in clear cell renal cell carcinoma according to multiple databases and experimental verification. Upregulated cytoskeleton-associated protein 2-like protein is an independent prognostic factor, which might activate the JAK–STAT signaling pathway, the P53 signaling pathway, the TGF-β signaling pathway, the WNT signaling pathway, etc., in clear cell renal cell carcinoma. Protein–protein interaction analysis and co-expression analysis suggest that cytoskeleton-associated protein 2-like protein might interact with some proliferation proteins. Immune infiltration analysis indicates that cytoskeleton-associated protein 2-like protein may affect the level of activated CD4+ memory T cells, M1 macrophages, CD8+ T cells, and neutrophils in clear cell renal cell carcinoma. More M1 macrophage infiltrations in tumor tissues with higher cytoskeleton-associated protein 2-like protein were validated by clear cell renal cell carcinoma tumor tissues.

Conclusion: Cytoskeleton-associated protein 2-like protein is upregulated in clear cell renal cell carcinoma tissues, which may promote progression of the disease. Cytoskeleton-associated protein 2-like protein is a potential target for prognostic markers and a potential treatment target in clear cell renal cell carcinoma.