DcR3-associated risk score: correlating better prognosis and enhanced predictive power in colorectal cancer

TL;DR

High DcR3 levels in colorectal cancer are linked to better survival and immune response, while a new risk score model identifies patients with worse outcomes.

Contribution

A novel DcR3-associated risk score model is developed to predict prognosis and immune features in colorectal cancer.

Findings

High DcR3 levels correlate with improved survival and favorable clinical features in early-stage colorectal cancer.

The DcR3-associated risk score model identifies patients with poor prognosis and advanced-stage disease.

DcR3 is linked to immune-related pathways and higher Tumor Infiltrating Lymphocytes in colorectal cancer patients.

Abstract

Decoy receptor 3 (DcR3), a novel soluble protein belonging to the tumor necrosis factor receptor (TNFR) family, has been previously associated with tumorigenesis in various cancers. However, in our study, we unexpectedly found that DcR3 may promote patient survival time in colorectal cancer (CRC). Through an analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we discovered that high levels of DcR3 are associated with improved overall survival (OS) and disease-free survival (DFS) in CRC patients. Further investigation revealed that DcR3 is correlated with favorable clinical features in Metastasis 0 (M0) and stage I/II CRC patients, suggesting it may act as a suppressive factor in CRC. Gene Set Enrichment Analysis (GSEA) demonstrated that the high DcR3 group is enriched in the IL-17 signaling pathway and other immune-related pathways, and Single Sample Gene Set Enrichment Analysis (ssGSEA) revealed a higher abundance of Tumor Infiltrating Lymphocytes (TIL) in the DcR3 high group. To better understand the function of DcR3, we constructed a DcR3-associated riskscore (DARS) model using machine learning, comprising three genes (DPP7, KDM3A, and TMEM86B). The DARS model indicated that high riskscore patients have an unfavorable prognosis, and it is associated with advanced stages (III/IV), T3/4 tumors, and N1/2 lymph node involvement. Additionally, high riskscore group exhibited more frequent gene mutations, such as TTN, MUC16, and SYNE1, with SYNE1 mutation being related to poor prognosis. Intriguingly, DcR3 showed higher expression in the low riskscore group. These results suggest that DcR3 could serve as a potential prognostic biomarker in CRC and may play a crucial role in favorably modulating the immune response in this malignancy.

The online version contains supplementary material available at 10.1007/s12672-024-01082-1.

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