Document Type : Original Article(s)

Authors

• Hadis Musavi ^{1, 2}
• Fereshteh Ahmadipour ³
• Tayebeh Azramezani Kopi ⁴
• Zahra Yazdani ⁵
• Fatemeh Gorjinezhad ⁶
• Fariba Ghodrati ⁷
• Abouzar Bagheri ¹
• Masoumeh Karimi ⁸
• Abbas Khonakdar-Tarsi ^{1, 9}

¹ Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

² Thalassemia Research Center, Hemoglobinophaty Institute, Mazandaran University of Medical Sciences, Sari, Iran

³ Department of Biochemistry and Molecular Biology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

⁴ Department of Clinical Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran

⁵ Department of Immunology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

⁶ Department of Biotechnology Bacterial, Sana University, Sari, Iran

⁷ Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

⁸ Department of Radiation Oncology, Babol University of Medical Sciences, Babol, Iran

⁹ Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran

Abstract

Background: Breast cancer is molecularly heterogeneous, highlighting the need to identify circulating molecular alterations. This study aimed to investigate the expression of Beta-site amyloid precursor protein-cleaving enzyme-1 antisense RNA (BACE1-AS) and Sirtuin 1 (SIRT1) in peripheral blood leukocytes of patients with breast cancer and to explore their molecular characteristics and potential clinical relevance using molecular and bioinformatic analyses.
Method: This case–control study included 30 treatment-naive breast cancer patients and 30 healthy controls. BACE1-AS and SIRT1 expression were quantified by quantitative real-time polymerase chain reaction. The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data from 1,098 tumors and 114 adjacent normal tissues were analyzed for expression, molecular subtypes, survival, correlations, diagnostic performance, and co-expression. Statistical analyses used R version 4.4 and GraphPad Prism version 9.5. A two-sided P < 0.05 was considered to be statistically significant.
Results: Leukocyte BACE1-AS (fold change = 10.18, P < 0.001) and SIRT1 (fold change = 5.05, P < 0.001) were significantly higher in patients than controls. Their leukocyte expression was not significantly correlated (r = 0.18, P = 0.53). In TCGA-BRCA, BACE1-AS showed subtype-dependent expression, a weak positive correlation with SIRT1 (r = 0.14), and good tissue-based diagnostic performance (area under the curve (AUC) = 0.79). Co-expression analysis indicated enrichment of networks related to cellular stress adaptation and genome maintenance. Leukocyte BACE1-AS showed poor diagnostic performance (AUC = 0.57).
Conclusion: BACE1-AS was associated with subtype-dependent expression and stress- and genome-maintenance-related networks but does not support standalone blood-based biomarker use. Further mechanistic studies are warranted.

Highlights

Keywords

• BACE1-AS
• SIRT1
• TCGA-BRCA
• Breast neoplasms
• RNA, Long noncoding

Main Subjects

• Cancer Diagnosis