ABSTRACT
Background: Acute appendicitis (AA) is one of the most prevalent acute abdominal diseases and appendectomy is the definitive treatment of appendicitis. However, whether appendicitis and appendectomy cause colorectal cancer (CRC) is controversial. The results of observational studies are contradictory, but randomized controlled trials (RCT) cannot be conducted. Methods: Data of appendectomy, AA, and CRC were obtained from the IEU Open GWAS project. We selected several Genome-wide association studies (GWAS) summary statistics for CRC: statistics for colon cancer (CC) were obtained from MRC-IEU and Neale lab, respectively; statistics for rectum cancer (RC) were obtained from MRC-IEU and FinnGen, respectively; statistics for CRC were provided by Sakaue S et al. Mendelian randomization (MR) was used to evaluate the causal relationships between exposure and outcomes. Inverse variance weighting (IVW) was the most important analysis method. Meta-analysis was used to summarize the results of IVW to increase the reliability and sensitivity analysis was used to evaluate the robustness of the results. Results: According to the results of IVW, appendectomy did not increase risk of CC: MRC-IEU (OR:1.009, 95%CI:0.984-1.035, P=0.494), Neale lab (OR:1.016, 95%CI:0.993-1.040, P=0.174); Appendectomy also did not increase risk of RC: MRC-IEU(OR:0.994, 95%CI:0.974-1.014, P=0.538), FinnGen(OR:2.791, 95%CI:0.013-580.763, P=0.706); Appendectomy also did not increase risk of CRC: Sakaue S(OR:1.382, 95%CI:0.301-6.352, P=0.678). Appendicitis did not increase risk of CC: MRC-IEU(OR:1.000, 95%CI:0.999-1.001, P=0.641), Neale lab(OR:1.000, 95%CI:1.000-1.001, P=0.319); Appendicitis also did not increase risk of RC: MRC-IEU(OR:1.000, 95%CI:0.999-1.000, P=0.361), FinnGen(OR:0.903, 95%CI:0.737-1.105, P=0.321); Appendicitis also did not increase risk of CRC: Sakaue S (OR:1.018, 95%CI:0.950-1.091, P=0.609). The results of Meta-analysis also showed appendectomy (P=0.459) and appendicitis (P=0.999) did not increase the risk of CRC. Conclusions: Appendectomy and appendicitis do not increase the risk of colorectal cancer. More clinical trials are needed in the future to verify the causal relationships.
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.