SPARCL1 Is a Novel Prognostic Biomarker and Correlates with Tumor Microenvironment in Colorectal Cancer

Abstract

Background. Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) plays an important role in tumor pathogenesis. We aim to evaluate the clinical significance and potential biological roles of SPARCL1 in colorectal cancer (CRC). Methods. Datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were downloaded to evaluate the expression levels of SPARCL1 in CRC. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of SPARCL1. Then, comprehensive database search was conducted for published clinical studies to explore clinical significance of SPARCL1. In addition, coexpression genes of SPARCL1 were identified through the cBioPortal database and enrichment analysis of SPARCL1 and its coexpression genes were performed by the “clusterProfiler” R package. Finally, the correlations between SPARCL1 and tumor microenvironment scores, tumor-infiltrating immune cells in CRC were determined by “ESTIMATE” and “GSVA” R packages. Results. SPARCL1 was significantly downregulated in CRC tissues, and SPARCL1 showed high accuracy for diagnosis of primary CRC in both GEO and TCGA datasets. Pooled results from published clinical studies showed SPARCL1 expression was associated with differentiation ( $\text{OR}=1.89$ , 95% CI: 1.38-2.59), tumor stage ( $\text{OR}=0.47$ , 95% CI: 0.29-0.77), distant metastasis ( $\text{OR}=0.53$ , 95% CI: 0.33-0.84), and overall survival ( $\text{HR}=0.56$ , 95% CI: 0.43-0.74). SPARCL1 and its top 300 coexpression genes were involved in several KEGG pathways, such as focal adhesion, cell adhesion molecules, PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, and ECM-receptor interaction. Besides, the SPARCL1 expression was significantly correlated with stromal score, immune score, ESTIMATE score, and diverse immune cells. Conclusion. SPARCL1 significantly correlated with clinicopathological features and tumor microenvironment in CRC.