Document Type : Original Article(s)
Authors
- Zahra Roshanizadeh 1, 2
- Mohammad Reza Haghshenas 2
- Amin Ramezani 2
- Neda Shajari 1, 2
- Sedigheh Tahmasebi 3
- Majid Akrami 4
- Abbas Ghaderi 1, 2
1 Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
2 Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
3 Department of General Surgery, Lymphedema Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
4 Breast Diseases Research Cancer, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract
Background: The targeted therapy using breast cancer (BC)-associated biomarkers has significantly minimized the side effects of BC treatment. This study aims to elucidate the role of Nectin2, NUF2, and Nectin4 gene expression in the pathogenesis of BC.
Method: In this case-control study, the expression of Nectin2, Nectin4, and NUF2 genes was investigated through real-time polymerase chain reaction assay in 46 tumor tissues from BC patients and 46 adjacent non-tumorous tissues as a control group. Data were analyzed using SPSS-21 software, employing independent t-tests and one-way ANOVA. A P-value of <0.05 was considered statistically significant.
Results: The results demonstrated a significant increase in the expression of the NUF2 gene in tumor tissues compared with adjacent normal tissues (P = 0.005, fold change = 3.7). No statistically significant difference was observed in the expression of Nectin2 and Nectin4 between the tumor and adjacent tissues. However, higher expression of Nectin2 was noted in the early stages of the disease, particularly in subtypes with estrogen receptor-positive (ER+), progesterone receptor positive (PR+), and human epidermal growth factor receptor 2 negative (HER2-). Furthermore, the expression of NUF2 and Nectin4 was elevated in advanced stages and triple-negative BC (TNBC) subtypes. Notably, the expression of these three genes was higher in patients aged ≤ 45 years.
Conclusion: The findings suggest that the expression levels of NUF2, Nectin2, and Nectin4 genes may influence the initiation, progression, and pathogenesis of BC subtypes.
Highlights
Zahra Roshanizadeh (PubMed)
Abbas Ghaderi (Google Scholar)
Keywords
Main Subjects
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.30476/mejc.2024.100701.1997
- Vázquez GP, Pozo AG, Fuertes LT, Arevalillo J, Moros AZ, Gómez MF, et al. A novel approach to triplenegative breast cancer molecular classification reveals a luminal immune-positive subgroup with good prognoses. Sci Rep. 2019;9(1):1538. doi: 10.1038/s41598-018-38364-y.
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492. Erratum in: CA Cancer J Clin. 2020;70(4):313.
- Anders CK, Johnson R, Litton J, Phillips M, Bleyer A. Breast cancer before age 40 years. Semin Oncol. 2009;36(3): 237-49. doi: 10.1053/j.seminoncol.2009.03.001.
- Guestini F, McNamara KM, Ishida T, Sasano H. Triple negative breast cancer chemosensitivity and chemoresistance: current advances in biomarkers indentification. Expert Opin Ther Targets. 2016;20(6):705-20. doi: 10.1517/14728222.2016.1125469.
- Perrot I, Michaud HA, Paoli MG, Augier S, Docquier A, Gros L, et al. Blocking antibodies targeting the Cd39/Cd73 immunosuppressive pathway unleash immune responses in combination cancer therapies. Cell Rep. 2019; 27(8):2411-25.e2419. doi: 10.1016/j.celrep.2019.04.091.
- Smazynski J, Hamilton PT, Thornton S, Milne K, Wouters MC, Webb JR, et al. The immune suppressive factors Cd155 and Pd-L1 show contrasting expression patterns and immune correlates in ovarian and other cancers. Gynecol Oncol. 2020;158(1):167-77. doi: 10.1016/j.ygyno.2020.04.689.
- Johnston RJ, Lee PS, Strop P, Smyth M J. Cancer immunotherapy and the Nectin family. Annu Rev Cancer Biol.2021;5:203-19. doi:10.1146/annurev-cancerbio-060920-084910.
- Liu X, An T, Li D, Fan Z, Xiang cP, Li C, et al. Structure of the heterophilic interaction between the Nectin-like 4 and Nectin-like 1 molecules. Proc Natl Acad Sci USA. 2019;116(6): 2068-77. doi: 10.1073/pnas.1810969116.
- Zhu Y, Paniccia A, Schulick AC, Chen W, Koenig MR, Byers JT, et al . Identification of Cd112r as a novel checkpoint for human T cells. J Exp Med. 2016;213(2):167-76. doi: 10.1084/jem.20150785.
- Salda LD, Massimini M, Romanucci M, Palmieri C, Perillo A, Grieco V, et al. Nectin-4 and P63 immunohistochemical expression in canine prostate tumourigenesis. Vet Comp Oncol. 2019;17(3): 298-307. doi: 10.3390/cancers14112727.
- Xing C, Wang Z, Zhu Y, Zhang C, Liu M, Hu X, et al. Integrate analysis of the promote function of Cell division cycle-associated protein family to pancreatic adenocarcinoma. Int J Med Sci. 2021;18(3):672-84. doi: 10.7150/ijms.53243.
- Ramezani A. CtNorm: Real time PCR cycle of threshold (Ct) normalization algorithm. J Microbiol Methods. 2021;187:106267. doi: 10.1016/j.mimet.2021.106267.
- Zhai X, Yang Z, Liu X, Dong Z, Zhou D. Identification of Nuf2 and Fam83d as potential biomarkers in triple-negative breast cancer. PeerJ. 2020;8:e9975. doi: 10.7717/peerj.9975.
- Lv S, Xu W, Zhang Y, Zhang J, Dong X. NUF2 as an anticancer therapeutic target and prognostic factor in breast cancer. Int J Oncol. 2020;57(6):1358-67. doi: 10.3892/ijo.2020.5141.
- Stamm H, Klingler F, Grossjohann EM, Muschhammer J, Vettorazzi E, Heuser M, et al. Immune checkpoints Pvr and Pvrl2 Are prognostic markers in Aml and their blockade represents a new therapeutic option. Oncogene. 2018;37:5269-80. doi: 10.1038/s41388-018-0288-y.
- Lanzel E, Robinson RA, Zimmerman MB, Pourian A, Hellstein JW. The use of immunohistochemistry in detection of perineural invasion in mucoepidermoid carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;121(6):636-42. doi: 10.1016/j.oooo.2016.01.026.
- Rabet M, Cabaud O, Josselin E, Finetti P, Castellano R, Farina A, et al. Nectin-4: a new prognostic biomarker for efficient therapeutic targeting of primary and metastatic triple-negative breast cancer. Ann Oncol. 2017;28(4):769-76. doi: 10.1093/annonc/mdw678.
- Zeindler J, Soysal SD, Piscuoglio S, Ng C, Mechera R, Isaak A, et al. Nectin-4 expression is an independent prognostic biomarker and associated with better survival in triple-negative breast cancer.Front Med (Lausanne). 2019;6:200-12. doi: 10.3389/fmed.2019.00200.
- Bernhardt SM, Dasari P, Walsh D, Townsend AR, Price TJ, Ingman WV. Hormonal modulation of breast cancer gene expression: implications for intrinsic subtyping in premenopausal women. Front Oncol. 2016;6:241-52. doi: 10.3389/fonc.2016.00241.
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