Analysis of exportins expression unveils their prognostic significance in colon adenocarcinoma: insights from public databases

Abstract

Colon cancer remains a significant health burden globally, necessitating deeper investigation. Identification and targeting of prognostic markers can significantly improve the current therapeutic approaches for colon cancer. The differential nuclear transport (import and export) of cellular proteins, plays an important role in tumor progression. Exportins, critical mediators of nuclear export, have emerged as potential players in cancer pathogenesis. However, their precise roles and prognostic significance in colon adenocarcinoma remain elusive. This study was designed to comprehensively analyse the expression and prognostic significance of all seven exportins in Colon Adenocarcinoma (COAD) using the online public database. We used public databases UALCAN, C-Bio portal, Human Protein Atlas (HPA), and DAVID, to investigate exportins in COAD patients. Kaplan-Meier plotter, Gene ontology (GO), TIMER, STRING, and KEGG were used to analyse data and draw conclusions. Our observations showed a significant correlation of exportins expression with clinical parameters, used to predict a patient's prognosis in general, such as advancing tumor stage, overall/relapse-free survival, and immune cell infiltrations. Mutation analysis showed the presence of amplifications, missense mutations in XPO2 and XPO4, and deep deletions in XPO7 genes contributing to disease progression and patients survival. This study highlights the potential use of exportins as novel prognostic biomarkers and therapeutic targets for colon adenocarcinoma progression and management.

Keywords: Colon adenocarcinoma (COAD); Exportins; Expression; Mutation; Prognosis.

Fig. 1

A Differential mRNA Expression of exportins in Colon Adenocarcinoma using TCGA database: A Heatmap from UALCAN database shows the mRNA expression of exportins. B Immunohistochemistry analysis of exportins in Colon Adenocarcinoma using HPA (Human Protein Atlas) database: Representative picture showing expression of XPO1, XPO2, XPO5, XPO6, XPO7 in Colon Adenocarcinoma and control tissue

Fig. 2

Box plot showing a correlation between exportins (XPO1, XPO2, XPO4, XPO5, XPO6, XPO7, and XPOT) mRNA expression and stage of tumor in Colon Adenocarcinoma using TGCA database in ULCAN analysis. Significant differences in expression between tumor and normal tissues, and between tumor stages are indicated by asterisks (*P < .05, **P < .01, ***P < .001)

Fig. 3

Overall Survival (OS) and Relapse Free Survival (RFS) analysis using Kaplan–Meier Plotter Database in Colon Adenocarcinoma patients: Figure shows the overall survival (A–G) and relapse-free survival (I-VII) of patients with high and low expression levels. Compared to the median expression value, of various exportins (XPO1, XPO2, XPO4, XPO5, XPO6, XPO7, and XPOT). A P-value of < .05 has been considered as statistically significant

Fig. 4

Genetic alteration analysis using cBioportal database in Colon Adenocarcinoma patients. A showing cBioportal onco-print with percentage of Genetic alteration in Colon Adenocarcinoma patient. B Survival analysis indicates that genetic alterations in exportins are associated with poor overall survival in patients. C Illustrating the types of mutations, mRNA expression levels, and their proportions contained in exportins (XPO1, XPO2, XPO4, XPO5, XPO6, XPO7, and XPOT)

Fig. 5

Correlation of exportins expression with the level of infiltrated immune cell using TIMER database: The Y-axis of all the graphs shows the expression (Log2 TPM) of respective exportin and the X-axis shows the level of immune cells (CD8⁺, T-cell; CD4 + T-cell; B cell; Macrophage and Neutrophil) infiltration in tumor tissue of Colon Adenocarcinoma patients. The first graph in each panel shows the correlation of exportins expression with the purity of the tumor. "tumor purity" is the proportion of cancer cells out of the total number of cells

Fig. 6

Protein–protein interaction network using STRING analysis: A Protein–protein interaction network resulting from the total 70 co-expressed genes (10 of each exportin) analysed in STRING. B Categorising the top two highly co-expressed genes (with the highest Spearman correlation coefficient) to each exportin (total 14) in different biological processes involved in cancer progression

Fig. 7

Gene Ontology functional analysis and KEGG pathway analysis: A total of 70 co-expressed genes (10 of each exportin) were analysed using the DAVID database. A GO enrichment analysis identifying and illustrating the significance of enriched GO terms associated with 70 co-expressed proteins. Each bubble represents a GO term. The size of the bubble corresponds to the number of genes (out of 70) associated with that particular GO term. B a visual representation of the relationships between GO terms. Gene Ontology graph of biological processes, cellular component, and molecular function, and KEGG pathway analysis