SPP1 AS A PROGNOSTIC BIOMARKER IN COLORECTAL CANCER: IMPLICATIONS FOR IMMUNE INFILTRATION IN ATHLETES AND FITNESS ENTHUSIASTS

Abstract

Background: Secretory phosphoprotein 1 (SPP1), also known as Osteopontin, is part of the small integrin-binding ligand N-linked glycoprotein family. Its overexpression in various cancers, including colorectal cancer (CRC), has been linked to prognosis. However, its role in the survival and immune infiltration in CRC, particularly in athletes and fitness enthusiasts, requires further investigation. Methods: Utilizing data from The Cancer Genome Atlas (TCGA) and the Genotype Tissue Expression Project (GTEx), we analyzed the expression profiles and clinical data of CRC patients, focusing on the relationship between SPP1 expression and cancer development. Wilcoxon rank tests compared SPP1 expression in normal and cancerous colorectal tissues. The predictive power of SPP1 in CRC was assessed using the receiver operating characteristic (ROC) curve. Logistic regression and Wilcoxon rank sum tests were used to correlate SPP1 expression with clinical features. Kaplan-Meier survival analysis, Progno Scan database, and Cox multivariate regression analysis evaluated SPP1's prognostic significance. R-package Cluster profiler enrichment analysis identified SPP1's biological functions and signaling pathways. Correlations between SPP1 and immune-infiltrating cells were appraised using single-sample gene set enrichment analysis (ssGSEA) and TIMER database, with further exploration of SPP1 and immune cell gene markers through TIMER and GEPIA databases. Results: SPP1 was found to be highly expressed in CRC, significantly more so than in normal colorectal tissues, with an AUC of 0.846 indicating high accuracy in CRC prognosis prediction. SPP1 expression correlated with pathological stage and disease[1]specific survival (DSS), with overexpression leading to reduced overall survival (OS), DSS, and disease-free survival (DFS). Multivariable Cox regression analysis confirmed SPP1 as an independent prognostic biomarker for CRC (HR = 1.459; 95% CI: 1.030-2.067; P = 0.033). SPP1 was associated with various biological functions and signaling pathways. It also showed a positive correlation with the infiltration levels of macrophages, dendritic cells (DCs), CD8+ T cells, and neutrophils in CRC. SPP1 was strongly correlated with immune gene markers, including TAM, DC, T cell exhaustion, and Tregs. Conclusion: SPP1's elevated expression in CRC is closely associated with poor immune infiltration and prognosis. In athletes and fitness enthusiasts, who might experience unique immune system challenges due to their intense physical regimes, SPP1's role becomes particularly crucial. Understanding SPP1's impact on immune infiltration in this group could lead to tailored therapeutic approaches in CRC, positioning SPP1 as a promising prognostic biomarker in this demographic.