Immune ULBP1 is Elevated in Colon Adenocarcinoma and Predicts Prognosis

Abstract

<b>Background:</b> Colon adenocarcinoma (COAD) is still the main cause of cancer deaths worldwide. Although immunotherapy has made progress in recent years, there is still a need to improve diagnosis, prognosis, and treatment tools. UL-16 binding protein 1 (ULBP1) is a ligand that activates the receptor natural killer cell group 2 receptor D (NKG2D) and plays an important immunomodulatory role. We aimed to investigate the clinical significance of <i>ULBP1</i> in COAD. <b>Methods:</b> We obtained the relevant data from The Cancer Genome Atlas (TCGA). A total of 438 patients with COAD were included in this study, with a mean age of 67.1 ± 13.03 years old, of which 234 (53.42%) were male. The diagnostic value of COAD tumor tissues and adjacent tissues was analyzed by ROC curve. Univariate and multivariate survival analysis investigated the prognostic value of <i>ULBP1</i> gene, and Gene Set Enrichment Analysis (GSEA) curve was performed to analyze the biological process and enriched enrichment pathway of <i>ULBP1</i> in COAD. Combination survival analysis investigated the combined prognostic effect of prognostic genes. <b>Results:</b> <i>ULBP1</i> gene had a high diagnostic value in COAD [AUC (TCGA) = 0.959; AUC (Guangxi) = 0.898]. Up-regulated <i>ULBP1</i> gene of patients with COAD predicted a worse prognosis compared to those patients with down-regulated <i>ULBP1</i> gene (Adjusted HR = 1.544, 95% CI = 1.020-2.337, <i>p</i> = 0.040). The GSEA showed that <i>ULBP1</i> was involved in the apoptotic pathway and biological process of T cell mediated cytotoxicity, regulation of natural killer cell activation, and T cell mediated immunity of COAD. The combination survival analysis showed that the combination of high expression of <i>ULBP1</i>, <i>AARS1</i>, and <i>DDIT3</i> would increase the 2.2-fold death risk of COAD when compared with those of low expression genes. <b>Conclusion:</b> The immune-related <i>ULBP1</i> gene had diagnostic and prognostic value in COAD. The combination of <i>ULBP1</i>, <i>AARS1</i>, and <i>DDIT3</i> genes could improve the prognostic prediction performance in COAD.