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Erschienen in: Wiener klinische Wochenschrift 17-18/2019

22.08.2019 | original article

Serum nectin-2 and nectin-4 are diagnostic in lung cancer: which is superior?

verfasst von: Kayhan Erturk, Sule Karaman, Nergiz Dagoglu, Murat Serilmez, Derya Duranyildiz, Faruk Tas

Erschienen in: Wiener klinische Wochenschrift | Ausgabe 17-18/2019

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Summary

Nectins are immunoglobulin-like molecules that are involved in cell to cell adhesion by forming tight junctions and homophilic/heterophilic interactions. This study aimed to analyze serum nectin‑2 and nectin‑4 levels in lung cancer patients and to evaluate the prognostic, diagnostic and predictive strengths. Data from 74 lung cancer patients were retrospectively examined and enzyme-linked immunosorbent assays (ELISA) were used to measure serum nectin‑2 and nectin‑4 concentrations. A total number of 40 age and sex-adjusted healthy controls were also enrolled in the study. The median serum nectin‑2 and nectin‑4 levels of the patients were significantly higher than those of controls (p < 0.001); however, neither biomarker was found to be associated with clinicopathological parameters, (p > 0.05), and furthermore they were found not to be correlated with either overall survival or progression-free survival (p > 0.05). Even though both markers showed high diagnostic values, serum nectin‑2 was found superior to both serum nectin‑4 and serum nectin-2 + nectin‑4 combinations in the diagnosis of lung cancer according to higher sensitivity, specificity and predictive values. Serum nectin‑2 and nectin‑4 might be used in lung cancer diagnosis but the diagnostic importance of nectin‑2 is higher. The prognostic and predictive strengths in cancer are controversial. Furthermore, the interactions with tumor microenvironments and the potentials as therapeutic targets for malignancies have yet to be elucidated.
Literatur
1.
Zurück zum Zitat Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Adv Exp Med Biol. 2016;893:1–19.CrossRefPubMed Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Adv Exp Med Biol. 2016;893:1–19.CrossRefPubMed
2.
3.
Zurück zum Zitat Ou SH, Ahn JS, De Petris L, Govindan R, Yang JC, Hughes B, et al. Alectinib in Crizotinib-refractory ALK-rearranged non-small-cell lung cancer: a phase II global study. J Clin Oncol. 2016;34:661–8.CrossRefPubMed Ou SH, Ahn JS, De Petris L, Govindan R, Yang JC, Hughes B, et al. Alectinib in Crizotinib-refractory ALK-rearranged non-small-cell lung cancer: a phase II global study. J Clin Oncol. 2016;34:661–8.CrossRefPubMed
4.
Zurück zum Zitat Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014;110:55–52.CrossRefPubMed Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014;110:55–52.CrossRefPubMed
5.
Zurück zum Zitat Besse B, Adjei A, Baas P, Meldgaard P, Nicolson M, Paz-Ares L, et al. Panel Members; ESMO. 2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease. Ann Oncol. 2014;25:1475–1474.CrossRefPubMed Besse B, Adjei A, Baas P, Meldgaard P, Nicolson M, Paz-Ares L, et al. Panel Members; ESMO. 2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease. Ann Oncol. 2014;25:1475–1474.CrossRefPubMed
6.
Zurück zum Zitat Takai Y, Miyoshi J, Ikeda W, Ogita H. Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation. Nat Rev Mol Cell Biol. 2008;9:603–15.CrossRefPubMed Takai Y, Miyoshi J, Ikeda W, Ogita H. Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation. Nat Rev Mol Cell Biol. 2008;9:603–15.CrossRefPubMed
7.
Zurück zum Zitat Sakisaka T, Ikeda W, Ogita H, Fujita N, Takai Y. The roles of nectins in cell adhesions: cooperation with other cell adhesion molecules and growth factor receptors. Curr Opin Cell Biol. 2007;19:593–592.CrossRefPubMed Sakisaka T, Ikeda W, Ogita H, Fujita N, Takai Y. The roles of nectins in cell adhesions: cooperation with other cell adhesion molecules and growth factor receptors. Curr Opin Cell Biol. 2007;19:593–592.CrossRefPubMed
8.
Zurück zum Zitat Yamada A, Fujita N, Sato T, Okamoto R, Ooshio T, Hirota T, et al. Requirement of nectin, but not cadherin, for formation of claudin-based tight junctions in annexin II-knockdown MDCK cells. Oncogene. 2006;25:5085–5082.CrossRefPubMed Yamada A, Fujita N, Sato T, Okamoto R, Ooshio T, Hirota T, et al. Requirement of nectin, but not cadherin, for formation of claudin-based tight junctions in annexin II-knockdown MDCK cells. Oncogene. 2006;25:5085–5082.CrossRefPubMed
9.
Zurück zum Zitat Morita H, Nandadasa S, Yamamoto TS, Terasaka-Iioka C, Wylie C, Ueno N. Nectin‑2 and N‑cadherin interact through extracellular domains and induce apical accumulation of F‑actin in apical constriction of Xenopus neural tube morphogenesis. Development. 2010;137:1315–25.CrossRefPubMedPubMedCentral Morita H, Nandadasa S, Yamamoto TS, Terasaka-Iioka C, Wylie C, Ueno N. Nectin‑2 and N‑cadherin interact through extracellular domains and induce apical accumulation of F‑actin in apical constriction of Xenopus neural tube morphogenesis. Development. 2010;137:1315–25.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Yamada A, Irie K, Fukuhara A, Ooshio T, Takai Y. Requirement of the actin cytoskeleton for the association of nectins with other cell adhesion molecules at adherens and tight junctions in MDCK cells. Genes Cells. 2004;9:843–55.CrossRefPubMed Yamada A, Irie K, Fukuhara A, Ooshio T, Takai Y. Requirement of the actin cytoskeleton for the association of nectins with other cell adhesion molecules at adherens and tight junctions in MDCK cells. Genes Cells. 2004;9:843–55.CrossRefPubMed
11.
Zurück zum Zitat Nakanishi H, Takai Y. Roles of nectins in cell adhesion, migration and polarization. Biol Chem. 2004;385:885–882.CrossRefPubMed Nakanishi H, Takai Y. Roles of nectins in cell adhesion, migration and polarization. Biol Chem. 2004;385:885–882.CrossRefPubMed
12.
Zurück zum Zitat Reymond N, Fabre S, Lecocq E, Adelaïde 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;276:43205–15.CrossRefPubMed Reymond N, Fabre S, Lecocq E, Adelaïde 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;276:43205–15.CrossRefPubMed
13.
Zurück zum Zitat Fabre S, Reymond N, Cocchi F, Menotti L, Dubreuil P, Campadelli-Fiume G, et al. Prominent role of the Ig-like V domain in trans-interactions of nectins. Nectin3 and nectin 4 bind to the predicted C‑C′-C″-D beta-strands of the nectin1 V domain. J Biol Chem. 2002;277:27006–13.CrossRefPubMed Fabre S, Reymond N, Cocchi F, Menotti L, Dubreuil P, Campadelli-Fiume G, et al. Prominent role of the Ig-like V domain in trans-interactions of nectins. Nectin3 and nectin 4 bind to the predicted C‑C′-C″-D beta-strands of the nectin1 V domain. J Biol Chem. 2002;277:27006–13.CrossRefPubMed
14.
Zurück zum Zitat Matsushima H, Utani A, Endo H, Matsuura H, Kakuta M, Nakamura Y, et al. The expression of nectin-1alpha in normal human skin and various skin tumours. Br J Dermatol. 2003;148:755–62.CrossRefPubMed Matsushima H, Utani A, Endo H, Matsuura H, Kakuta M, Nakamura Y, et al. The expression of nectin-1alpha in normal human skin and various skin tumours. Br J Dermatol. 2003;148:755–62.CrossRefPubMed
15.
Zurück zum Zitat Athanassiadou AM, Patsouris E, Tsipis A, Gonidi M, Athanassiadou P. The significance of Survivin and Nectin‑4 expression in the prognosis of breast carcinoma. Folia Histochem Cytobiol. 2011;49:26–33.CrossRefPubMed Athanassiadou AM, Patsouris E, Tsipis A, Gonidi M, Athanassiadou P. The significance of Survivin and Nectin‑4 expression in the prognosis of breast carcinoma. Folia Histochem Cytobiol. 2011;49:26–33.CrossRefPubMed
16.
Zurück zum Zitat 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;134:835–45.CrossRefPubMedPubMedCentral 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;134:835–45.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat 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;69:6694–703.CrossRefPubMed 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;69:6694–703.CrossRefPubMed
19.
Zurück zum Zitat 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;18:160–71.CrossRefPubMed 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;18:160–71.CrossRefPubMed
21.
Zurück zum Zitat Lampugnani MG, Orsenigo F, Gagliani MC, Tacchetti C, Dejana E. Vascular endothelial cadherin controls VEGFR‑2 internalization and signaling from intracellular compartments. J Cell Biol. 2006;174:593–604.CrossRefPubMedPubMedCentral Lampugnani MG, Orsenigo F, Gagliani MC, Tacchetti C, Dejana E. Vascular endothelial cadherin controls VEGFR‑2 internalization and signaling from intracellular compartments. J Cell Biol. 2006;174:593–604.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat 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;6:179–90.PubMedPubMedCentral 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;6:179–90.PubMedPubMedCentral
24.
Zurück zum Zitat Izumi H, Hirabayashi K, Nakamura N, Nakagohri T. Nectin expression in pancreatic adenocarcinoma: nectin‑3 is associated with a poor prognosis. Surg Today. 2015;45:487–94.CrossRefPubMedPubMedCentral Izumi H, Hirabayashi K, Nakamura N, Nakagohri T. Nectin expression in pancreatic adenocarcinoma: nectin‑3 is associated with a poor prognosis. Surg Today. 2015;45:487–94.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Jang SM, Han H, Jun YJ, Jang SH, Min KW, Sim J, et al. Clinicopathological significance of CADM4 expression, and its correlation with expression of E‑cadherin and Ki-67 in colorectal adenocarcinomas. J Clin Pathol. 2012;65:902–6.CrossRefPubMed Jang SM, Han H, Jun YJ, Jang SH, Min KW, Sim J, et al. Clinicopathological significance of CADM4 expression, and its correlation with expression of E‑cadherin and Ki-67 in colorectal adenocarcinomas. J Clin Pathol. 2012;65:902–6.CrossRefPubMed
27.
Zurück zum Zitat Maniwa Y, Nishio W, Okita Y, Yoshimura M. Expression of nectin 3: novel prognostic marker of lung adenocarcinoma. Thorac Cancer. 2012;3:175–81.CrossRefPubMed Maniwa Y, Nishio W, Okita Y, Yoshimura M. Expression of nectin 3: novel prognostic marker of lung adenocarcinoma. Thorac Cancer. 2012;3:175–81.CrossRefPubMed
29.
Zurück zum Zitat Challita-Eid PM, Satpayev D, Yang P, An Z, Morrison K, Shostak Y, et al. Enfortumab Vedotin antibody-drug conjugate targeting Nectin‑4 is a highly potent therapeutic agent in multiple Preclinical cancer models. Cancer Res. 2016;76:3003–13.CrossRefPubMed Challita-Eid PM, Satpayev D, Yang P, An Z, Morrison K, Shostak Y, et al. Enfortumab Vedotin antibody-drug conjugate targeting Nectin‑4 is a highly potent therapeutic agent in multiple Preclinical cancer models. Cancer Res. 2016;76:3003–13.CrossRefPubMed
Metadaten
Titel
Serum nectin-2 and nectin-4 are diagnostic in lung cancer: which is superior?
verfasst von
Kayhan Erturk
Sule Karaman
Nergiz Dagoglu
Murat Serilmez
Derya Duranyildiz
Faruk Tas
Publikationsdatum
22.08.2019
Verlag
Springer Vienna
Erschienen in
Wiener klinische Wochenschrift / Ausgabe 17-18/2019
Print ISSN: 0043-5325
Elektronische ISSN: 1613-7671
DOI
https://doi.org/10.1007/s00508-019-01537-4

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