CCDC68 predicts poor prognosis in patients with colorectal cancer: a study based on TCGA data.

ABSTRACT

Background: The prognostic value of coiled-coil domain containing 68 (CCDC68) in colorectal cancer (CRC) is unclear. We evaluated the role of CCDC68 in CRC based on The Cancer Genome Atlas (TCGA) database. Methods: Patients with CRC were collected from TCGA. We determined CCDC68 expression using the Wilcoxon rank sum test. Logistic analysis was applied to study the relationship between CCDC68 expression and clinicopathologic features. Cox regression and the Kaplan-Meier method were used to determine the predictive value of CCDC68 on clinical outcomes in CRC patients. Gene Set Enrichment Analysis (GSEA) and the single-sample Gene Set Enrichment Analysis (ssGSEA) were also conducted to annotate the biological function of CCDC68. Results: Reduced CCDC68 expression in CRC was significantly correlated with N stage [odds ratio (OR) =0.95 for N1/N2 vs. N0], M stage (OR =0.91 for M1 vs. M0), pathologic stage (OR =0.95 for stage III/stage IV vs. stage I/stage II), neoplasm type (OR =0.92 for rectum adenocarcinoma vs. colon adenocarcinoma), tumor protein 53 (TP53) status [OR =0.93 for Mut (mutant) vs. WT (wild type)], and kirsten rat sarcoma viral oncogene (KRAS) status (OR =0.97 for Mut vs. WT) (all P values <0.05). Kaplan-Meier survival analysis showed that low CCDC68 expression had a poorer overall survival (OS) (P=0.008), progression-free interval (PFI) (P=0.006), and disease-specific survival (DSS) (P=0.023). Cox regression analysis revealed that CCDC68 was a risk factor for OS (P=0.047), PFI (P=0.048), and DSS (P=0.038). GSEA demonstrated that the chemokine signaling pathway, the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, high-affinity IgE receptor (FcεRI)-mediated nuclear factor-κB (NF-κB) activation, cell adhesion molecules (CAMs), complement cascade, FcεRI-mediated mitogen-activated protein kinase (MAPK) activation, intestinal immune network for immunoglobulin A (IgA) production, and Toll-like receptor signaling pathway were differentially enriched in the high CCDC68 expression phenotype, while the Wnt signaling pathway was significantly enriched in the low CCDC68 expression phenotype. SsGSEA found that CCDC68 expression was positively correlated with T helper 2 (Th2) and T helper cells. Conclusions: CCDC68 expression may be a potential prognostic molecular marker for poor survival in CRC. Moreover, CCDC68 may participate in the development of CRC via multiple signaling pathways.