Pan-cancer analysis reveals the roles of XPO1 in predicting prognosis and tumorigenesis

Background: Exportin 1 (XPO1), a nuclear export protein, participates in many biological processes, including mRNA transport, nucleocytoplasmic transport, nuclear protein export, regulation of mRNA stability, and drug response. XPO1 plays key roles in many cancer types and may serve as a potential biomarker. It is significant to systematically elucidate the roles of XPO1 in various cancer types in terms of function, molecular biology, immunology, and clinical relevance.

Methods: Data from UCSC Xena, CCLE, and CBioPortal were analyzed for the investigation of the differential expression of XPO1 across multiple cancer types. Clinical data were acquired to analyze the influence of XPO1 on the clinical characteristics of patients, such as survival outcome and clinical stage. The roles of XPO1 in the onset and progression of multiple cancers were expounded in terms of genetic changes at the molecular level [including tumor mutational burden (TMB), microsatellite instability (MSI), copy number variation (CNV), methylation, and gene co-expression], biological pathway changes, and the immune microenvironment.

Results: XPO1 was overexpressed in various tumor types, which may be related to CNV. Clinical data analysis revealed that XPO1 may serve as a risk factor in tumors, such as adrenocortical carcinoma, liver hepatocellular carcinoma, and low-grade glioma, thereby affecting patient prognosis. XPO1 in multiple tumor types was also substantially correlated with clinical stage, patient gender, and patient age. In certain tumors, the expression level of XPO1 exerted a greater influence on TMB and MSI. It was also found that XPO1 inhibited the activity of immune cells in the tumor immune microenvironment, such as CD8+ T cells, and affected biological pathways, such as the cell cycle and oxidative phosphorylation, and drove the expression of cancer driver genes, immune checkpoint genes, and highly mutated genes.

Conclusions: XPO1 is a potential pan-cancer risk factor as it may jointly promote tumor onset and progression by inhibiting the immune response, influencing relevant biological pathways, and promoting mutations in other genes.