Adenylate cyclase family members have recently received attention as novel therapeutic targets. However, the significance of adenylate cyclase 9 (ADCY9) in breast cancer has not been elucidated. Here, we evaluated ADCY9 expression in breast cancer (BC) cell lines, and polymerase chain reaction array analysis was performed to determine the correlations between ADCY9 expression levels and 84 tumor-associated genes. The association of ADCY9 messenger RNA (mRNA) expression levels in clinical breast cancer specimens with patients' clinicopathological factors and prognosis was evaluated. The database of cancer cell line showed that estrogen receptor-positive and progesterone receptor-positive cells expressed higher ADCY9 mRNA levels. ADCY9 expression showed positive correlations with several oncogenes, such as TGFB1, CDKN1A, and BAX in the polymerase chain reaction array analysis. We defined the ratio of ADCY9 mRNA expression levels in breast cancer and adjacent noncancerous tissues as the "C/N ratio". Among 149 patients with BC, estrogen receptor-positive and progesterone receptor-positive patients exhibited higher C/N ratios than estrogen receptor-negative and progesterone receptor-negative patients, respectively. Patients in the lowest C/N ratio quartile experienced shorter prognosis periods. The C/N ratio of ADCY9 was found as an independent prognostic factor for disease-free survival. Thus, ADCY9 expression is high in hormone receptor-positive breast cancer, and its low expression indicates a poor prognosis in patients with breast cancer.
Keywords: ADCY9; breast cancer; estrogen receptor; prognostic marker.