Expression Patterns and Relevance of FN3K, Nrf2, and NQO1 in Breast Cancers
Narasimha Murthy Beeraka1, Jin Zhang2, Chinnappa Apattira Uthaiah3, Churganova A Anastasia4, Junqi Liu5, Hemanth Vikram Poola Ramachandrappa1, Priyanka MK6, Namitha Bannimath7, Rajashree Deka8, Prasath Manogaran9, Karen D Souza1, Namratha Mandya Parashivamurthy10, Vladimir Nikolaevich Nikolenko4, Kirill Vladimirovich Bulygin4, Prashant Vishwanath3, Ruitai Fan1, Gurupadayya Bannimath11Department of Pharmaceutical chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India, 2Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, 3Center of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India, 4I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, 5Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, 6Department of Pathology, JSS Medical College, JSS Academy of Higher Education and Research (JSSAHER), Mysore, India, 7Department of Pharmacology, University of Galway, Galway, Ireland, 8Animal Physiology and Biochemistry Laboratory, Department of Zoology, Gauhati University, Assam, India, 9Department of Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu, 10Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India,
Objectives: Previous studies described the prognostic significance of nuclear factor erythroid 2-related factor 2 (Nrf2) in breast cancers. Nrf2 is significantly involved in inducing antioxidant responses in tumor cells to neutralize oxidative stress. A recent study by V Sanghvi et al 2019 demonstrated the role of fructosamine-3-kinase (FN3K) in Nrf2 degly cation in cancer but the prognostic significance based on pathological, clinical relevance has remained unknown in breast cancer patients. In this study, we determined the relevance of FN3K based on Prediction Analysis of Microarray 50 (PAM-50)algorithm based breast cancer classification & FN3K gene expression patterns on tumor-node-metastasis (TNM) wise using The Cancer Genome Atlas (TCGA) database subsequently determined its expression patterns in luminal A (HR+/HER2 ? (human epidermal growth factor receptor 2), ER (Estrogen Receptor positive)+/PR+(Progesterone Receptor positive), ER+/PR?, and ER?/PR+), luminal B (HR+/HER2+, ER+/PR+, ER+/PR?, and ER?/PR+ ), HER 2+ (ER-, PR-, HER2+), and TNBCs (Triple-Negative Breast Cancers) (ER-, PR-, HER2-) along differential protein expression patterns of Nrf2, and NQO1(NAD(P)H quinone oxidoreductase) (markers of oxidative stress). Methods: R-statistical computing, Kaplan Meier survival curves, immunohistochemistry, Western blotting was used to explore the expression of FN3K relative to the expression of Nrf2, and NQO1. Results: We observed significantly a higher FN3K gene expression in luminal B when compared to its expression in other cancer types, Basal, Her2, Luminal A, and normal tissue as per TCGA database. FN3K gene expression is significantly higher (P<0.05) in stage IV, and T4 compared to the other stages or sizes of breast cancer. Correlated expression of both genes confers significant implications in the patient’s overall survival. A control study pertinent to FN3K, Nrf2, and NQO1 immunoreactivity is performed and the expression was highly evident in luminal A, luminal B when compared to HER 2+, TNBCs and adjacent normal breast tissue. Breast cancer disease-specific survival was determined based on the FN3K and Nrf2 gene expression patterns. Conclusion: Hence, this study described the relevance of FN3K-Nrf2 signaling in the breast cancers. Keywords: FN3K, Nrf2, NQO1, PAM50 algorithms, breast cancer, TNM stages (tumor (T), nodes (N), and metastases (M))
Cite This Article
Beeraka N, Zhang J, Uthaiah C, Anastasia C, Liu J, Ramachandrappa H, et al. Expression Patterns and Relevance of FN3K, Nrf2, and NQO1 in Breast Cancers. EJMO. 2024; 8(1): 88-105
Corresponding Author: Narasimha Murthy Beeraka