Skip to main content
Erschienen in: Medical Oncology 2/2014

01.02.2014 | Original Paper

High expression of CXCR-2 correlates with lymph node metastasis and predicts unfavorable prognosis in resected esophageal carcinoma

verfasst von: Ping Sui, Pingping Hu, Tiehong Zhang, Xiangwei Zhang, Qi Liu, Jiajun Du

Erschienen in: Medical Oncology | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

CXC chemokines have been reported to play critical roles in tumor growth, angiogenesis, invasion and metastasis of various human cancers. However, expression of CXC chemokines type 2 (CXCR2) and its association with clinicopathological characters and patients’ prognosis in esophageal cancer are scarcely reported. We retrospectively collected clinicopathologic characteristics of 95 esophageal cancer patients undergoing esophagectomies. Immunohistochemistry was used to detect the expression of CXCR2. The survival was analyzed by the Kaplan–Meier method. Univariate and multivariate analyses were then performed to determine the relationship between CXCR2 and the clinical characteristics and to analyze whether CXCR2 expression was a significant independent prognostic factor for esophageal cancer patients. CXCR2 was highly expressed in 57.9 % of the randomly selected specimens. The expression of CXCR2 was significantly related to lymph node metastasis (P = 0.044) and predicted poor overall status in operable esophageal cancer patients (P = 0.012). Cox proportional hazard analysis regression analysis indicated that CXCR2 expression (P = 0.030) and lymphatic metastasis (P < 0.001) may serve as independent prognostic markers for esophageal cancer patients. Our results demonstrate that CXCR2 significantly correlates with lymph node metastasis and is a poor prognostic factor in resected esophageal squamous cell carcinoma.
Literatur
1.
Zurück zum Zitat Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.PubMedCrossRef Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.PubMedCrossRef
2.
Zurück zum Zitat Hannelien V, Karel G, Jo VD, Sofie S. The role of CXC chemokines in the transition of chronic inflammation to esophageal and gastric cancer. Biochim Biophys Acta. 2012;1825(1):117–29.PubMed Hannelien V, Karel G, Jo VD, Sofie S. The role of CXC chemokines in the transition of chronic inflammation to esophageal and gastric cancer. Biochim Biophys Acta. 2012;1825(1):117–29.PubMed
3.
Zurück zum Zitat Richmond A. Chemokine research moves on. Exp Cell Res. 2011; 317(5):553–555. PubMed PMID: 21241691. Pubmed Central PMCID: 3056356. Richmond A. Chemokine research moves on. Exp Cell Res. 2011; 317(5):553–555. PubMed PMID: 21241691. Pubmed Central PMCID: 3056356.
4.
Zurück zum Zitat Raman D, Sobolik-Delmaire T, Richmond A. Chemokines in health and disease. Exp Cell Res. 2011; 317(5):575–589. PubMed PMID: 21223965. Pubmed Central PMCID: 3063402. Raman D, Sobolik-Delmaire T, Richmond A. Chemokines in health and disease. Exp Cell Res. 2011; 317(5):575–589. PubMed PMID: 21223965. Pubmed Central PMCID: 3063402.
5.
Zurück zum Zitat Keeley EC, Mehrad B, Strieter RM. Chemokines as mediators of tumor angiogenesis and neovascularization. Exp Cell Res. 2011; 317(5):685–690. PubMed PMID: 21040721. Pubmed Central PMCID: 3073599. Keeley EC, Mehrad B, Strieter RM. Chemokines as mediators of tumor angiogenesis and neovascularization. Exp Cell Res. 2011; 317(5):685–690. PubMed PMID: 21040721. Pubmed Central PMCID: 3073599.
6.
Zurück zum Zitat Han L, Jiang B, Wu H, Wang X, Tang X, Huang J, et al. High expression of CXCR2 is associated with tumorigenesis, progression, and prognosis of laryngeal squamous cell carcinoma. Med Oncol. 2012;29(4):2466–72.PubMedCrossRef Han L, Jiang B, Wu H, Wang X, Tang X, Huang J, et al. High expression of CXCR2 is associated with tumorigenesis, progression, and prognosis of laryngeal squamous cell carcinoma. Med Oncol. 2012;29(4):2466–72.PubMedCrossRef
7.
Zurück zum Zitat Ijichi H. Inhibition of CXCLs/CXCR2 axis in the tumor microenvironment might be a potent therapeutics for pancreatic cancer. OncoImmunology. 2012;1(4):569–71.PubMedCentralPubMedCrossRef Ijichi H. Inhibition of CXCLs/CXCR2 axis in the tumor microenvironment might be a potent therapeutics for pancreatic cancer. OncoImmunology. 2012;1(4):569–71.PubMedCentralPubMedCrossRef
8.
Zurück zum Zitat Hertzer KM, Donald GW, Hines OJ. CXCR2: a target for pancreatic cancer treatment? Expert Opin Ther Targets. 2013; 17(6):667–680. PubMed PMID: 23425074. Pubmed Central PMCID: 3686651. Hertzer KM, Donald GW, Hines OJ. CXCR2: a target for pancreatic cancer treatment? Expert Opin Ther Targets. 2013; 17(6):667–680. PubMed PMID: 23425074. Pubmed Central PMCID: 3686651.
9.
Zurück zum Zitat Vandercappellen J, Van Damme J, Struyf S. The role of CXC chemokines and their receptors in cancer. Cancer Lett. 2008;267(2):226–44.PubMedCrossRef Vandercappellen J, Van Damme J, Struyf S. The role of CXC chemokines and their receptors in cancer. Cancer Lett. 2008;267(2):226–44.PubMedCrossRef
10.
Zurück zum Zitat Wang B, Hendricks DT, Wamunyokoli F, Parker MI. A growth-related oncogene/CXC chemokine receptor 2 autocrine loop contributes to cellular proliferation in esophageal cancer. Cancer Res. 2006;66(6):3071–7.PubMedCrossRef Wang B, Hendricks DT, Wamunyokoli F, Parker MI. A growth-related oncogene/CXC chemokine receptor 2 autocrine loop contributes to cellular proliferation in esophageal cancer. Cancer Res. 2006;66(6):3071–7.PubMedCrossRef
11.
Zurück zum Zitat Allegretti M, Cesta MC, Garin A, Proudfoot AE. Current status of chemokine receptor inhibitors in development. Immunol Lett. 2012;145(1–2):68–78.PubMedCrossRef Allegretti M, Cesta MC, Garin A, Proudfoot AE. Current status of chemokine receptor inhibitors in development. Immunol Lett. 2012;145(1–2):68–78.PubMedCrossRef
12.
Zurück zum Zitat Yanagawa J, Walser TC, Zhu LX, Hong L, Fishbein MC, Mah V, et al. Snail promotes CXCR2 ligand-dependent tumor progression in non-small cell lung carcinoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2009; 15(22):6820–6829. PubMed PMID: 19887480. Pubmed Central PMCID: 2783274. Yanagawa J, Walser TC, Zhu LX, Hong L, Fishbein MC, Mah V, et al. Snail promotes CXCR2 ligand-dependent tumor progression in non-small cell lung carcinoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2009; 15(22):6820–6829. PubMed PMID: 19887480. Pubmed Central PMCID: 2783274.
13.
Zurück zum Zitat Garin A, Proudfoot AE. Chemokines as targets for therapy. Exp Cell Res. 2011;317(5):602–12.PubMedCrossRef Garin A, Proudfoot AE. Chemokines as targets for therapy. Exp Cell Res. 2011;317(5):602–12.PubMedCrossRef
14.
Zurück zum Zitat Singh S, Sadanandam A, Nannuru KC, Varney ML, Mayer-Ezell R, Bond R, et al. Small-molecule antagonists for CXCR2 and CXCR1 inhibit human melanoma growth by decreasing tumor cell proliferation, survival, and angiogenesis. Clin Cancer Res Off J Am Assoc Cancer Res. 2009;15(7):2380–6.CrossRef Singh S, Sadanandam A, Nannuru KC, Varney ML, Mayer-Ezell R, Bond R, et al. Small-molecule antagonists for CXCR2 and CXCR1 inhibit human melanoma growth by decreasing tumor cell proliferation, survival, and angiogenesis. Clin Cancer Res Off J Am Assoc Cancer Res. 2009;15(7):2380–6.CrossRef
15.
Zurück zum Zitat Hu D, Du C, Xue W, Dou F, Yao Y, Gu J. The expression of chemokine receptors CCR6, CXCR2 and CXCR4 is not organ-specific for distant metastasis in colorectal cancer: a comparative study. Histopathology. 2013; 63(2):167–173. PubMed PMID: 23758411. Epub 2013/06/14. Eng. Hu D, Du C, Xue W, Dou F, Yao Y, Gu J. The expression of chemokine receptors CCR6, CXCR2 and CXCR4 is not organ-specific for distant metastasis in colorectal cancer: a comparative study. Histopathology. 2013; 63(2):167–173. PubMed PMID: 23758411. Epub 2013/06/14. Eng.
16.
Zurück zum Zitat Wente MN, Keane MP, Burdick MD, Friess H, Buchler MW, Ceyhan GO, et al. Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis. Cancer Lett. 2006;241(2):221–7.PubMedCrossRef Wente MN, Keane MP, Burdick MD, Friess H, Buchler MW, Ceyhan GO, et al. Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis. Cancer Lett. 2006;241(2):221–7.PubMedCrossRef
17.
Zurück zum Zitat Cheng WL, Wang CS, Huang YH, Tsai MM, Liang Y, Lin KH. Overexpression of CXCL1 and its receptor CXCR2 promote tumor invasion in gastric cancer. Ann Oncol Off J Eur Soc Med Oncology/ESMO. 2011;22(10):2267–76.CrossRef Cheng WL, Wang CS, Huang YH, Tsai MM, Liang Y, Lin KH. Overexpression of CXCL1 and its receptor CXCR2 promote tumor invasion in gastric cancer. Ann Oncol Off J Eur Soc Med Oncology/ESMO. 2011;22(10):2267–76.CrossRef
18.
Zurück zum Zitat Zhao M, Wimmer A, Trieu K, Discipio RG, Schraufstatter IU. Arrestin regulates MAPK activation and prevents NADPH oxidase-dependent death of cells expressing CXCR2. J Biol Chem. 2004;279(47):49259–67.PubMedCrossRef Zhao M, Wimmer A, Trieu K, Discipio RG, Schraufstatter IU. Arrestin regulates MAPK activation and prevents NADPH oxidase-dependent death of cells expressing CXCR2. J Biol Chem. 2004;279(47):49259–67.PubMedCrossRef
19.
Zurück zum Zitat Wang B, Khachigian LM, Esau L, Birrer MJ, Zhao X, Parker MI, et al. A key role for early growth response-1 and nuclear factor-B in mediating and maintaining GRO/CXCR2 proliferative signaling in esophageal cancer. Mol Cancer Res. 2009;7(5):755–64.PubMedCrossRef Wang B, Khachigian LM, Esau L, Birrer MJ, Zhao X, Parker MI, et al. A key role for early growth response-1 and nuclear factor-B in mediating and maintaining GRO/CXCR2 proliferative signaling in esophageal cancer. Mol Cancer Res. 2009;7(5):755–64.PubMedCrossRef
20.
Zurück zum Zitat Varney ML, Singh S, Li A, Mayer-Ezell R, Bond R, Singh RK. Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases. Cancer Lett. 2011; 300(2):180–188. PubMed PMID: 21035946. Pubmed Central PMCID: 2994987. Varney ML, Singh S, Li A, Mayer-Ezell R, Bond R, Singh RK. Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases. Cancer Lett. 2011; 300(2):180–188. PubMed PMID: 21035946. Pubmed Central PMCID: 2994987.
Metadaten
Titel
High expression of CXCR-2 correlates with lymph node metastasis and predicts unfavorable prognosis in resected esophageal carcinoma
verfasst von
Ping Sui
Pingping Hu
Tiehong Zhang
Xiangwei Zhang
Qi Liu
Jiajun Du
Publikationsdatum
01.02.2014
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 2/2014
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0809-z

Weitere Artikel der Ausgabe 2/2014

Medical Oncology 2/2014 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.