High expression levels of CXCL12 and CXCR4 predict recurrence of adamanti-nomatous craniopharyngiomas in children

Article type: Research Article

Authors: Gong, Jian^{a; c; 1} | Zhang, Haili^{b; 1} | Xing, Shushan^b | Li, Chunde^a | Ma, Zhenyu^a | Jia, Ge^{a; *} | Hu, Wanning^{b; *}

Affiliations: [a] Department of Pediatric Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China | [b] Department of Oncology, Tangshan People’s Hospital, Hebei United University, Hebei, China | [c] Beijing Neurosurgical Institute, Beijing, China

Correspondence: [*] Corresponding authors: Wanning Hu, Department of Oncology, Tangshan People’s Hospital, Hebei United University, No. 65 Victory Street, Tangshan, Hebei, China. Tel.: +86 10 67096756; Fax: +86 10 84113498; E-mail: wanninghu88@gmail.com; Ge Jia, Department of Pediatric Neurosurgery, Beijing Tiantan Hospital, 6 Tiantan Xili, Beijing 100050, China. Tel.: +86 10 67096756; Fax: +86 10 84113498; E-mail: jiage55@sina.com E-mail: wanninghu88@gmail.com; Ge Jia, Department of Pediatric Neurosurgery, Beijing Tiantan Hospital, 6 Tiantan Xili, Beijing 100050, China. Tel.: +86 10 67096756; Fax: +86 10 84113498; E-mail: jiage55@sina.com.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Adamantinomatous craniopharyngioma (ACP) is a benign but maldevelopmental tumor with a high recurrence rate. Objective:Theaim of this study was to investigate the dysregulated biological molecules that play important roles in the recurrence of ACP. Methods:We first performed microarray analysis on tumor samples from two pediatric patients with recurrent ACP and from two pediatric ACP patients without recurrence after a one-year follow-up. The expression of CXCL12 and CXCR4 in 45 specimens of pediatric ACP was further evaluated by immunohistochemistry. These results were correlated with the clinicopathological parameters and survival of the patients. Results:Four downregulated genes (APC, ITGA, MCAM, and TIMP4) and 16 upregulated genes (CST7, CTSK, CTSL1, CXCL12, CXCR4, FN1, FXYD5, ITGB3, MMP2, MMP3, MMP7, MMP9, NR4A3, PLAUR, TIMP2, and VEGFA) were found in the recurrent patients. CXCL12 and CXCR4 were highly expressed in 13 patients (28.9%) and 14 patients (31.1%), respectively. High levels of CXCL12 and CXCR4 expression were significantly associated with a poor recurrence-free survival and were the prognostic factors for ACP recurrence in pediatric patients. Conclusions:High levels of CXCL12 and CXCR4 expression were associated with ACP recurrence. The role of CXCL12 and CXCR4 in the development of brain tumors requires further research.

Keywords: Adamantinomatous craniopharyngioma, recurrence, CXCR4, CXCL12, Ki-67

DOI: 10.3233/CBM-140397

Journal: Cancer Biomarkers, vol. 14, no. 4, pp. 241-251, 2014