Pan-cancer analysis predicts CANT1 as a potential prognostic, immunologic biomarker

Abstract

Background: CANT1, calcium-activated nucleotidase 1, was reported to be upregulated in certain tumors. However, the function mechanism of CANT1 in pan-cancer is still unclear.

Methods: We utilized the Cancer Genome Atlas Program (TCGA) and UALCAN databases to analyze CANT1 expression at the level of mRNA, protein, and promoter methylation in pan-cancer, and the cBioportal database to study the frequency of gene changes for CANT1. Wilcoxon test was applied to discuss the correlation between CANT1 and clinicopathological features in different tumor types. The prognosis of CANT1 in pan-cancer was discussed by Cox regression. Spearman analysis was applied to discuss the relationship of CANT1 with tumor mutation burden(TMB), microsatellite instability(MSI), immune cell infiltration, and immune checkpoints. The association between CANT1 expression and drug sensitivity for pan-cancer was investigated by the GSCALite database. In addition, we collected 40 cases of lung adenocarcinoma (LUAD) and adjacent normal tissues for immunohistochemical staining and investigated the relationship between CANT1 and clinicopathology and prognosis in LUAD. Finally, the molecular pathways involved in CANT1-related genes in LUAD were analyzed by gene set enrichment analysis(GSEA).

Results: The CANT1 mRNA level was significant higher in 14 tumors, and CANT1 protein level was significant higher in 7 tumors compared with normal tissues. CANT1 expression was linked with the T stage, N stage, and pathological stage in some tumors, and overexpression CANT1 was associated with adverse overall survival(OS) and disease-specific survival(DSS) in kidney renal papillary cell carcinoma(KIRP), brain lower grade glioma(LGG), and LUAD. By Spearman correlation analysis, the results showed that CANT1 had a positive correlation with TMB and MSI in bladder urothelial carcinoma(BLCA), breast invasive carcinoma(BRCA), esophageal carcinoma(ESCA), LGG, and sarcoma(SARC). Furthermore, CANT1 was related to immune cell infiltration and immune checkpoints in several cancers. Drug sensitivity analysis suggested that CANT1 was inversely linked with three drugs. Immunohistochemical staining analysis showed that CANT1 expression was higher in LUAD than in normal tissues, and was related to N stage and pathological stage. Survival curves showed that CANT1 overexpression had poor OS and DSS. Time-dependent ROC curves revealed that the 1-year, 5-year, and 10-year OS and DSS in LUAD were above 0.5. CANT1-related genes in LUAD mainly participated in the pathway of dorso ventral axis formation, small cell lung cancer, DNA replication, O-glycan biosynthesis, and cell cycle.

Conclusion: CANT1 is considered a potential marker for prognosis in several tumors, and a promising target for tumor immunological treatment.

Keywords: CANT1; Immunity; Prognostic marker; pan-cancer.