Identification of Serotonin as a Predictive Marker for Breast Cancer Patients

Abstract

Qing-E Xie,1– 3,* Xin Du,4,* Mengyao Wang,1,2,5 Fenfen Xie,3 Zuoyang Zhang,6 Yunxia Cao,1,2,5,7,8 Yajing Liu1,2,5,7,8 1Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei, 230022, People’s Republic of China; 3Department of Histology and Embryology, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China; 4 901th Hospital of PLA Joint Logistic Support Force, Heifei, 230031, Anhui, People’s Republic of China; 5Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People’s Republic of China, Hefei, 230032, Anhui, People’s Republic of China; 6Department of Pathology, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China; 7Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, 230032, Anhui, People’s Republic of China; 8Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunxia Cao; Yajing Liu Email [email protected]; [email protected]: Cumulative evidence has demonstrated that breast cancer was the most commonly diagnosed cancer in women. Despite growing evidence for a link between serotonin and tumorigenesis, research on the expression of serotoninergic systems in the human breast cancer cell and tissue has only rarely been reported.Methods: First, immunofluorescence staining, ELISA and Western blotting were used to detect serotonin and melatoninergic systems in various breast cancer cell types. Then, serotonin expression was evaluated in the cultures of TPBC cell line BT-474 and TNBC cell line MDA-MB-231 using immunofluorescence assay. To further explore the diagnostic role of serotonin in breast cancer, serotonin expression was conducted in the TPBC and TNBC tumor sections by immunostaining analysis.Results: Our results suggested that both human breast cancer cells and human breast epithelial cell line could synthesize serotonin and melatonin. Unlike melatonin, serotonin levels varied significantly between human breast cancer and breast epithelial cell line (p< 0.01). In addition, serotonin N-acetyltransferase (NAT) and acetylserotonin methyltransferase (ASMT), the key enzymes in the pathway of melatonin synthesis from serotonin, were also detectable. In agreement with these findings of human breast cancer cell and human breast epithelial cell line, serotonin expression was also much higher in triple-negative (PR−, ER−, HER-2−) breast cancer (TNBC) and triple-positive breast cancer (TPBC) compared to para-carcinoma tissues (PCTs).Conclusion: Here, we provided evidence that the human breast cancer cell (MCF-7, Bcap-37) and human breast epithelial cell (MCF-10A) could synthesize intrinsic serotonin and melatonin, and serotonin expression was higher in the breast cancer tissue compared with PCT. The findings suggested that serotonin might be used as a predictive marker for breast cancer patients.Keywords: serotonin, melatonin, breast cancer, serotonin N-acetyltransferase, acetylserotonin methyltransferase

Keywords

• serotonin
• melatonin
• breast cancer
• serotonin n-acetyltransferase
• acetylserotonin methyltransferase