Non-coding ribonucleic acid-mediated CAMSAP1 upregulation leads to poor prognosis with suppressed immune infiltration in liver hepatocellular carcinoma

Abstract

Liver hepatocellular carcinoma (LIHC) is well-known for its unfavorable prognosis due to the lack of reliable diagnostic and prognostic biomarkers. Calmodulin-regulated spectrin-associated protein 1 (CAMSAP1) is a non-centrosomal microtubule minus-end binding protein that regulates microtubule dynamics. This study aims to investigate the specific role and mechanisms of CAMSAP1 in LIHC. We performed systematical analyses of CAMSAP1 and demonstrated that differential expression of CAMSAP1 is associated with genetic alteration and DNA methylation, and serves as a potential diagnostic and prognostic biomarker in some cancers, especially LIHC. Further evidence suggested that CAMSAP1 overexpression leads to adverse clinical outcomes in advanced LIHC. Moreover, the AC145207.5/LINC01748-miR-101–3p axis is specifically responsible for CAMSAP1 overexpression in LIHC. In addition to the previously reported functions in the cell cycle and regulation of actin cytoskeleton, CAMSAP1-related genes are enriched in cancer- and immune-associated pathways. As expected, CAMSAP1-associated LIHC is infiltrated in the suppressed immune microenvironment. Specifically, except for immune cell infiltration, it is significantly positively correlated with immune checkpoint genes, especially CD274 (PD-L1), and cancer-associated fibroblasts. Prediction of immune checkpoint blockade therapy suggests that these patients may benefit from therapy. Our study is the first to demonstrate that besides genetic alteration and DNA methylation, AC145207.5/LINC01748-miR-101-3p-mediated CAMSAP1 upregulation in advanced LIHC leads to poor prognosis with suppressed immune infiltration, representing a potential diagnostic and prognostic biomarker as well as a promising immunotherapy target for LIHC.