Coactosin-Like Protein 1 (COTL1) Could Be an Immunological and Prognostic Biomarker: From Pan-Cancer Analysis to Low-Grade Glioma Validation.

BACKGROUND: Cancer represents a widespread global health challenge impacting millions of individuals worldwide. Identifying new targets for cancer treatment is a crucial step in developing more effective therapies. Among these potential targets, Coactosin-like protein 1 (COTL1), a cytoskeleton-associated protein with critical roles in cell migration, adhesion, and signaling, has shown involvement in tumor progression.

METHODS: GSCA, TIMER, SangerBox database were used to explore the COTL1 expression across different tumor types. We employed the TCGA Pan-Atlas Cancer Genomics Dataset, which is available through the cBioportal platform, to explore genetic alterations in COTL1. We conduct a comprehensive analysis of COTL1, encompassing gene expression, clinical prognosis, RNA modification, immunotherapy, and cancer stemness through SangerBox database. Clinical samples were validated using immunohistochemistry.

RESULTS: Our analysis revealed that COTL1 is highly expressed in most cancers and correlates with decreased survival in Glioma, Glioblastoma multiforme, and pan-kidney cohorts. Furthermore, COTL1 was found to be associated with DNA and RNA stemness in 20 and 22 different tumor types, respectively. Additionally, COTL1 showed positive correlations with immunological checkpoints and immune infiltration cells. It was also linked to tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen (NEO), and programmed death ligand 1 (PD-L1), all of which are potential targets for immunotherapies. Moreover, a favorable relationship was demonstrated between genomic-instability markers such as heterozygosity (LOH), homologous recombination deficiency (HRD), and mutant allele tumor heterogeneity (MATH) with COTL1. Furthermore, our findings confirmed a positive correlation between COTL1 expression, CD8, and PD-L1 in LGG, as well as an association of high COTL1 expression with decreased patient survival in LGG.

CONCLUSION: Based on these compelling findings, COTL1 may hold significant clinical implications for the development of novel cancer therapies and serve as a potential target for tumors associated with immunotherapy in the future.