Downregulation of MICA/B tumor surface expressions and augmented soluble MICA serum levels correlate with disease stage in breast cancer

Article type: Research Article

Authors: Kshersagar, Jeevitaa^a | Damle, Mrunal N.^{a; b} | Bedge, Poonam^a | Jagdale, Rakhi^c | Tardalkar, Kishor^a | Jadhav, Dhanaji^d | Jagadale, Swapnali^a | Toro, Yashwant^e | Sharma, Rakesh^f | Joshi, Meghnad G.^{a; b;}

Affiliations: [a] Department of Stem Cells & Regenerative Medicine, D. Y. Patil Deemed to be University, D. Y. Patil Vidyanagar, Kasba Bawda, Kolhapur, Maharashtra, India | [b] Stem Plus Biotech, SMK Commercial Complex, Near Shivaji Maharaj Putla, Gaon Bhag, Sangli, Maharashtra, India | [c] Department of Pathology, Shri Siddhivinayak Ganpati Cancer Hospital, Miraj, Sangli, Maharashtra, India | [d] Department of Statistics, Yashavantrao Chavan Institute of Science, Satara, Maharashtra, India | [e] Department of Scientific and Industrial Research Organization, Shri Siddhivinayak Ganpati Cancer Hospital, Miraj, Sangli, Maharashtra, India | [f] Department of Obstetrics and Gynaecology, Dr. D Y Patil Medical College, Hospital and Research Institute, Kadamwadi, Kolhapur, Maharashtra, India

Correspondence: [*] Corresponding author: Dr. Meghnad G. Joshi, Professor and HOD, Department of Stem Cells and Regenerative Medicine, D. Y. Patil Education Society (Deemed to be University), Kasaba Bawada, Kolhapur 416006, Maharashtra, India. Tel.: +91 9767677772; E-mail: [email protected]

Abstract: OBJECTIVE:In this study, the profiling of the expression of major histocompatibility complex (MHC) class I-related chain A and B (MICA/B) in human breast cancer tumor tissue, saliva, and urine samples of breast cancer patients and control is carried out. MICA/B is ligand of NKG2D receptor expressed on malignant cells. The release of MICA/B from tumor tissue comprises an immune escape mechanism that impairs antitumor immunity. Based on this literature we explored the potential of soluble MICA (sMICA) as a marker in breast cancer (BC). METHODS:The expression was profiled by using immunohistochemistry (MICA/B), western blot (MICA/B) and ELISA (MICA). RESULTS:The optical density of western blot of MICA/B in different stages of BC illustrated significant difference as per one way analysis of variance and significant difference with stage III and IV by Dunnett’s multiple comparisons test respectively. Analysis of sMICA in serum, saliva and urine of BC patients revealed significantly higher levels (median 41.0 ± 4.1 pg/ml in pre-treatment sera, 181.9 ± 1.6 pg/ml in saliva and 90.7 ± 1.7 pg/ml in urine) than in control (median <1.2 pg/ml). The elevated levels of sMICA were related to the cancer stage. CONCLUSIONS:The elevated levels of sMICA were observed in patients with well differentiated cancer while the poor expression of sMICA was observed in patients with poorly differentiated tumors. Tumor immunity is impaired by the release of MICA in the biofluids and may be useful for detection and diagnosis of the stage of BC.

Keywords: Breast cancer, MICA/B, sMICA/B

DOI: 10.3233/BD-220023

Journal: Breast Disease, vol. 41, no. 1, pp. 471-480, 2022