Adenylate cyclase 9 expression level is associated with hormone receptor-positive breast cancer and predicts patient prognosis

Sep 21, 2026

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Adenylate cyclase family members are explored as therapeutic targets, yet adenylate cyclase 9 (ADCY9) has unclear relevance to breast cancer. ADCY9 expression was quantified in breast cancer cell lines, and polymerase chain reaction array profiling was used to correlate ADCY9 levels with 84 tumor-associated genes. In 149 clinical specimens, ADCY9 mRNA (C/N ratio) was higher in hormone receptor-positive tumors, positively linked to oncogenes, and the lowest C/N quartile showed shorter prognosis. The C/N ratio independently predicted disease-free survival, indicating that high ADCY9 marks hormone receptor-positive disease while low expression signals poor outcomes.

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CategoryResearch & Report

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Introduction

Materials and Methods

Sample collection

ORIGINAL PAPER Nagoya J. Med. Sci. 86. 665–682, 2024 doi:10.18999/nagjms.86.4.665 Adenylate cyclase 9 expression level is associated with hormone receptor-positive breast cancer and predicts patient prognosis Kayoko Sugino 1, Masahiro Shibata 1,2, Yayoi Adachi 1, Ikumi Soeda 1, Takahiro Ichikawa 1, Takahiro Inaishi 1, Emi Kanaya3, Mitsuro Kanda4, Masamichi Hayashi4 and Norikazu Masuda 1 1Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan 2Department of Surgery, Nagoya Ekisaikai Hospital, Nagoya, Japan 3Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan 4Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan ABSTRACT 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: breast cancer, ADCY9, estrogen receptor, prognostic marker Abbreviations: ADCY: adenylate cyclase BC: breast cancer C/N ratio: ratio of mRNA expression levels between cancerous and noncancerous tissues DFS: disease-free survival ER: estrogen receptor Received: January 15, 2024; accepted: May 17, 2024 Corresponding Author: Masahiro Shibata, MD, PhD Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan Tel: +81-52-744-2251, Fax: +81-52-744-2252, E-mail: [shibata.masahiro.f1@f.mail.nagoya-u.ac.jp](shibata.masahiro.f1@f.mail.nagoya-u.ac.jp) Kayoko Sugino et al HER2: human epidermal growth factor receptor 2 mRNA: messenger RNA PCR: polymerase chain reaction PgR: progesterone receptor This is an Open Access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view the details of this license, please visit ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)). INTRODUCTION Breast cancer (BC) is the most commonly diagnosed cancer among women.1 Medication therapies, including chemotherapy, endocrine therapy, and molecular targeting drugs, have recently been selected based on the expression status of the estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) in primary tumors. Although the prognosis of patients with BC has improved owing to the development of novel therapeutic drugs, metastatic BC remains difficult

FAQs

What role does ADCY9 expression play in hormone receptor-positive breast cancer?

ADCY9 mRNA levels are higher in estrogen receptor-positive and progesterone receptor-positive breast cancer compared with receptor-negative cases. This suggests ADCY9 is associated with hormone receptor-positive disease biology.

How was the relationship between ADCY9 and other genes assessed?

ADCY9 expression was measured in breast cancer cell lines, and polymerase chain reaction array analysis correlated ADCY9 levels with 84 tumor-associated genes. ADCY9 showed positive correlations with several oncogenes.

Does ADCY9 C/N ratio predict patient prognosis?

Yes. Patients in the lowest ADCY9 C/N ratio quartile experienced shorter prognosis periods. The ADCY9 C/N ratio was also found as an independent prognostic factor for disease-free survival.

Sep 21, 2026

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