Nectin-2 and Nectin-4 Adhesion Molecules in Patients with
Breast Cancer

ÜÇÜNCÜ, Muhammed Zubeyr; BADEMLER, Süleyman; VATANSEVER, Sezai; SERİLMEZ, Murat; AK, Naziye

doi:10.5505/tjo.2021.2697

Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer

Naziye AK, (İstanbul Üniversitesi Onkoloji Enstitüsü, Tıbbi Onkoloji Anabilim Dalı, İstanbul, Türkiye)

Murat SERİLMEZ, (İstanbul Üniversitesi Onkoloji Enstitüsü, Biyokimya Anabilim Dalı, İstanbul, Türkiye)

Muhammed Zubeyr ÜÇÜNCÜ, (Gelişim Üniversitesi Sağlık Bilimleri Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul, Türkiye)

Süleyman BADEMLER, (İstanbul Üniversitesi Onkoloji Enstitüsü, Genel Cerrahi Anabilim Dalı, İstanbul,Türkiye)

Sezai VATANSEVER (İstanbul Üniversitesi Onkoloji Enstitüsü, Tıbbi Onkoloji Anabilim Dalı, İstanbul,Türkiye)

Türk Onkoloji Dergisi

11 3

Yıl: 2021 Cilt: 36 Sayı: 2 Sayfa Aralığı: 165 - 170 Metin Dili: Türkçe DOI: 10.5505/tjo.2021.2697 İndeks Tarihi: 04-06-2022

Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer

Öz:

Evaluation of the nectin-2 and nectin-4 protein and mRNA expression levels is aimed in this study, with concerning diagnostic and predictive value in breast cancer patients. METHODS Sixty patients with pathologically and radiologically verified breast cancer who were treated at the Istanbul University, Institute of Oncology, between 2017 and 2018 are included in the study. Circulating nectin-2 and nectin-4 protein levels were evaluated by solid-phase enzyme-linked immunosorbent assay (Abbkine Scientific Co., Ltd.). For analyzing nectin-2- and nectin-4-specific mRNA in sera of the patients, circulating cell-free RNA was extracted from serum using a monophasic phenol and guanidine thiocyanate solution (Roche, Mannheim, Germany), according to the manufacturer’s protocol. RESULTS The median age of patients was 53 years. The mean tumor size was 30.21±17.32 mm. Forty-one patients were in the luminal group. Lymph node involvement was detected in 25 patients. The nectin-4 expression level was statistically significantly higher in those with Ki-67 ≥30 and those with positive distant metastasis compared to the other group. In addition, nectin-2 expression was higher in patients with Grade 3 tumors. CONCLUSION High levels of nectin-2 and nectin-4 expression in the serum of patients correlate with poor disease characteristics of breast cancer.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15- year survival: an overview of the randomised trials. Lancet 2005;365(9472):1687–717.
2. Park YH, Senkus-Konefka E, Im SA, Pentheroudakis G, Saji S, Gupta S, et al. Pan-Asian adapted ESMO clinical practice guidelines for the management of patients with early breast cancer: A KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS. Ann Oncol 2020;31(4):451–69.
3. Makki J. Diversity of breast carcinoma: histological subtypes and clinical relevance. Clin Med Insights Pathol 2015;8:23–31.
4. Sakisaka T, Takai Y. Biology and pathology of nectins and nectin-like molecules. Curr Opin Cell Biol 2004;16(5):513–21.
5. Takai Y, Nakanishi H. Nectin and afadin: novel organizers of intercellular junctions. J Cell Sci 2003;116(1):17–27.
6. Irie K, Shimizu K, Sakisaka T, Ikeda W, Takai Y. Roles and modes of action of nectins in cell-cell adhesion. Semin Cell Dev Biol 2004;15(6):643–56.
7. Nakanishi H, Takai Y. Roles of nectins in cell adhesion, migration and polarization. Biol Chem 2004;385(10):885–92.
8. Reymond N, Fabre S, Lecocq E, Adelaide J, Dubreuil P, Lopez M. Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through v domain interaction. J Biol Chem 2001;276(46):43205–15.
9. Takano A, Ishikawa N, Nishino R, Masuda K, Yasui W, Inai K, et al. identification of nectin-4 oncoprotein as a diagnostic and therapeutic target for lung cancer. Cancer Res 2009;69(16):6694–703.
10. Fabre-Lafay S, Garrido-Urbani S, Reymond N, Goncalves A, Dubreuil P, Lopez M. Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-alpha-converting enzyme (TACE)/ ADAM-17. J Biol Chem 2005;280(20):19543–50.
11. Oshima T, Sato S, Kato J, Ito Y, Watanabe T, Tsuji I, et al. Nectin-2 is a potential target for antibody therapy of breast and ovarian cancers. Mol Cancer 2013;12:60.
12. Fabre-Lafay S, Monville F, Garrido-Urbani S, Berruyer- Pouyet C, Ginestier C, Reymond N, et al. Nectin-4 is a new histological and serological tumor associated marker for breast cancer. BMC Cancer 2007;7:73.
13. Kanzaki N, Ogita H, Komura H, Ozaki M, Sakamoto Y, Majima T, et al. Involvement of the nectin-afadin complex in pdgf-induced cell survival. J Cell Sci 2008;121(12):2008–17.
14. Ikeda W, Nakanishi H, Miyoshi J, Mandai K, Ishizaki H, Tanaka M, et al. Afadin: a key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis. J Cell Biol 1999;146(5):1117–32.
15. Noyce RS, Bondre DG, Ha MN, Lin LT, Sisson G, Tsao MS, et al. Tumor cell marker PVRL4 (Nectin 4) is an epithelial cell receptor for measles virus. PLoS Pathog 2011;7(8):e1002240.
16. Karabulut M, Gunaldi M, Alis H, Afsar CU, Karabulut S, Serilmez M, et al. Serum nectin-2 levels are diagnostic and prognostic in patients with colorectal carcinoma. Clin Transl Oncol 2016;18(2):160–71.
17. Liang S, Yang Z, Li D, Miao X, Yang L, Zou Q, et al. The clinical and pathological significance of nectin-2 and DDX3 expression in pancreatic ductal adenocarcinomas. Dis Markers 2015;2015:379568.
18. Miao X, Yang ZL, Xiong L, Zou Q, Yuan Y, Li J, et al. Nectin-2 and DDX3 are biomarkers for metastasis and poor prognosis of squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder. Int J Clin Exp Pathol 2013;6(2):179–90.
19. Li M, Qiao D, Pu J, Wang W, Zhu W, Liu H. Elevated Nectin-2 expression is involved in esophageal squamous cell carcinoma by promoting cell migration and invasion. Oncol Lett 2018;15(4):4731–6.
20. Erturk K, Karaman S, Dagoglu N, Serilmez M, Duranyildiz D, Tas F. Serum Nectin-2 and Nectin-4 are diagnostic in lung cancer: which is superior? Wien Klin Wochenschr 2019;131(17–18):419–26.
21. Deuss FA, Gully BS, Rossjohn J, Berry R. Recognition of Nectin-2 by the natural killer cell receptor T cell immunoglobulin and ITIM domain (TIGIT). J Biol Chem 2017;292(27):11413–22.
22. Lattanzio R, Ghasemi R, Brancati F, Sorda RL, Tinari N, Perracchio L, et al. Membranous Nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal- a early breast cancer. Oncogenesis 2014;3(9):e118.
23. Derycke MS, Pambuccian SE, Gilks CB, Kalloger SE, Ghidouche A, Lopez M, et al. Nectin 4 overexpression in ovarian cancer tissues and serum: potential role as a serum biomarker. Am J Clin Pathol 2010;134(5):835–45.

APA	AK N, SERİLMEZ M, ÜÇÜNCÜ M, BADEMLER S, VATANSEVER S (2021). Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer. , 165 - 170. 10.5505/tjo.2021.2697
Chicago	AK Naziye,SERİLMEZ Murat,ÜÇÜNCÜ Muhammed Zubeyr,BADEMLER Süleyman,VATANSEVER Sezai Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer. (2021): 165 - 170. 10.5505/tjo.2021.2697
MLA	AK Naziye,SERİLMEZ Murat,ÜÇÜNCÜ Muhammed Zubeyr,BADEMLER Süleyman,VATANSEVER Sezai Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer. , 2021, ss.165 - 170. 10.5505/tjo.2021.2697
AMA	AK N,SERİLMEZ M,ÜÇÜNCÜ M,BADEMLER S,VATANSEVER S Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer. . 2021; 165 - 170. 10.5505/tjo.2021.2697
Vancouver	AK N,SERİLMEZ M,ÜÇÜNCÜ M,BADEMLER S,VATANSEVER S Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer. . 2021; 165 - 170. 10.5505/tjo.2021.2697
IEEE	AK N,SERİLMEZ M,ÜÇÜNCÜ M,BADEMLER S,VATANSEVER S "Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer." , ss.165 - 170, 2021. 10.5505/tjo.2021.2697
ISNAD	AK, Naziye vd. "Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer". (2021), 165-170. https://doi.org/10.5505/tjo.2021.2697

APA	AK N, SERİLMEZ M, ÜÇÜNCÜ M, BADEMLER S, VATANSEVER S (2021). Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer. Türk Onkoloji Dergisi, 36(2), 165 - 170. 10.5505/tjo.2021.2697
Chicago	AK Naziye,SERİLMEZ Murat,ÜÇÜNCÜ Muhammed Zubeyr,BADEMLER Süleyman,VATANSEVER Sezai Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer. Türk Onkoloji Dergisi 36, no.2 (2021): 165 - 170. 10.5505/tjo.2021.2697
MLA	AK Naziye,SERİLMEZ Murat,ÜÇÜNCÜ Muhammed Zubeyr,BADEMLER Süleyman,VATANSEVER Sezai Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer. Türk Onkoloji Dergisi, vol.36, no.2, 2021, ss.165 - 170. 10.5505/tjo.2021.2697
AMA	AK N,SERİLMEZ M,ÜÇÜNCÜ M,BADEMLER S,VATANSEVER S Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer. Türk Onkoloji Dergisi. 2021; 36(2): 165 - 170. 10.5505/tjo.2021.2697
Vancouver	AK N,SERİLMEZ M,ÜÇÜNCÜ M,BADEMLER S,VATANSEVER S Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer. Türk Onkoloji Dergisi. 2021; 36(2): 165 - 170. 10.5505/tjo.2021.2697
IEEE	AK N,SERİLMEZ M,ÜÇÜNCÜ M,BADEMLER S,VATANSEVER S "Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer." Türk Onkoloji Dergisi, 36, ss.165 - 170, 2021. 10.5505/tjo.2021.2697
ISNAD	AK, Naziye vd. "Nectin-2 and Nectin-4 Adhesion Molecules in Patients with Breast Cancer". Türk Onkoloji Dergisi 36/2 (2021), 165-170. https://doi.org/10.5505/tjo.2021.2697