Elevated Adenylyl Cyclase 9 Expression Is a Potential Prognostic Biomarker for Patients with Colon Cancer

BACKGROUND: Adenylyl cyclase 9 (ADCY9) is an enzyme that modulates signal transduction by producing the second messenger, cyclic adenosine monophosphate (cAMP). The aim of the present study was to investigate the association of ADCY9 expression with clinicopathological features and disease-free survival of colon cancer patients. MATERIAL/METHODS: Immunohistochemistry staining with ADCY9 antibody was performed on a tissue microarray. Immunoreactivity scores (IRS) were recorded and applied for association analysis. ADCY9 mRNA expression and clinicopathological information were also extracted from the TCGA colon cancer dataset and analyzed using univariate and multivariate Cox proportional hazards models. RESULTS: ADCY9 IRS was significantly higher (P=0.002) in tumor tissues (6.40±1.26, n=200) than in adjacent normal samples (4.13±0.83, n=8). The IRS and mRNA expression of ADCY9 were correlated to colon cancer TNM staging. Longer disease-free survival was observed in patients with lower ADCY9 expression (P=0.001). In the multivariate models, ADCY9 expression level (hazard ratio [HR] 5.495, 95% confidence interval [CI] 1.753–17.227, P=0.003), and distant metastasis (HR 4.329, 95% CI 1.374–13.636, P=0.012) were still associated with disease-free survival. CONCLUSIONS: High ADCY9 expression is a poor prognostic factor for disease-free survival in colon cancer.