Prognostic implication of neuropilin-1 upregulation in human nasopharyngeal carcinoma

Diagnostic Pathology

Yao Wang²  Dongsheng Gu¹  Junying Wang¹  Xin Zhang¹  Peizhong Li¹  Yu Xu¹ 

[1] Department of Otorhinolaryngology, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing Road West, Huai’an, Jiangsu 223300, P. R. China;Pharmaceutical Preparation Section, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing Road West, Huai’an, Jiangsu 223300, P. R. China

关键词: Prognosis;    Immunohistochemistry;    Expression;    Neuropilin-1;    Nasopharyngeal carcinoma;   

Others  :  804618
DOI  :  10.1186/1746-1596-8-155

 received in 2013-08-06, accepted in 2013-08-18,  发布年份 2013

【 摘 要 】

Objective

As a receptor for both vascular endothelial growth factors and semaphorin, neuropilin-1 (NRP-1) is reported to be up-regulated in cells of several cancers. However, its roles in human nasopharyngeal carcinoma (NPC) are still unclear. Therefore, the goal of this study was to investigate the expression pattern of NRP-1 in NPC tissues, to clarify the clinical significance of NRP-1 expression in NPC as well as the potential prognostic implication of NRP-1 expression.

Methods

Immunohistochemistry was performed to detect the expression of NRP-1 in tumor tissue samples from 266 NPC patients. The association of NRP-1 protein expression with the clinicopathological characteristics and the prognosis of NPC were subsequently assessed.

Results

Immunohistochemical analysis showed that 176 of 266 (66.17%) paraffin-embedded archival NPC biopsies showed high expression of NRP-1, but no non-cancerous nasopharyngeal specimens showed positive expression of NRP-1. In addition, high NRP-1 expression was significantly associated with advanced clinical stage (P = 0.02), positive recurrence (P = 0.001) and metastasis status (P = 0.001) of NPC. Moreover, the NPC patients with higher NRP-1 expression had shorter overall survival, whereas patients with lower NRP-1 expression had better survival (P < 0.001). Furthermore, the multivariate analysis indicated that the overexpression of NRP-1 protein was an independent prognostic factor for overall survival (P = 0.001) in NPC patients.

Conclusion

These findings suggest for the first time that NRP-1 upregulation may be a novel biomarker for the prediction of advanced tumor progression and unfavorable prognosis in NPC patients who may benefit from alternative treatment strategy and targeted treatment.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1507827881105018 webcite.

【 授权许可】

   
2013 Xu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Glastonbury CM, Salzman KL: Pitfalls in the staging of cancer of nasopharyngeal carcinoma. Neuroimaging Clin N Am 2013, 23:9-25.
• [2]Han BL, Xu XY, Zhang CZ, Wu JJ, Han CF, Wang H, Wang X, Wang GS, Yang SJ, Xie Y: Systematic review on Epstein-Barr virus (EBV) DNA in diagnosis of nasopharyngeal carcinoma in Asian populations. Asian Pac J Cancer Prev 2012, 13:2577-2581.
• [3]Lee AW, Lin JC, Ng WT: Current management of nasopharyngeal cancer. Semin Radiat Oncol 2012, 22:233-244.
• [4]Hughes J, Alusi G, Wang Y: Gene therapy and nasopharyngeal carcinoma. Rhinology 2012, 50:115-121.
• [5]Ho FC, Tham IW, Earnest A, Lee KM, Lu JJ: Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: a meta-analysis of clinical evidence. BMC Cancer 2012, 12:98. BioMed Central Full Text
• [6]Mao Y, Zhang DW, Zhu H, Lin H, Xiong L, Cao Q, Liu Y, Li QD, Xu JR, Xu LF, Chen RJ: LMP1 and LMP2A are potential prognostic markers of extranodal NK/T-cell lymphoma, nasal type (ENKTL). Diagn Pathol 2012, 7:178. BioMed Central Full Text
• [7]Pellet-Many C, Frankel P, Jia H, Zachary I: Neuropilins: structure, function and role in disease. Biochem J 2008, 411:211-226.
• [8]Geretti E, Shimizu A, Klagsbrun M: Neuropilin structure governs VEGF and semaphorin binding and regulates angio-genesis. Angiogenesis 2008, 11:31-39.
• [9]Grünewald FS, Prota AE, Giese A, Ballmer-Hofer K: Structure-function analysis of VEGF receptor activation and the role of coreceptors in angiogenic signaling. Biochim Biophys Acta 1804, 2010:567-580.
• [10]Chen L, Miao W, Tang X, Zhang H, Wang S, Luo F, Yan J: The expression and significance of neuropilin-1 (NRP-1) on glioma cell lines and glioma tissues. J Biomed Nanotechnol 2013, 9:559-563.
• [11]Pallaoro A, Braun GB, Moskovits M: Quantitative ratiometric discrimination between noncancerous and cancerous prostate cells based on neuropilin-1 overexpression. Proc Natl Acad Sci U S A 2011, 108:16559-16564.
• [12]Jubb AM, Strickland LA, Liu SD, Mak J, Schmidt M, Koeppen H: Neuropilin-1 expression in cancer and development. J Pathol 2012, 226:50-60.
• [13]Akagi M, Kawaguchi M, Liu W, McCarty MF, Takeda A, Fan F, Stoeltzing O, Parikh AA, Jung YD, Bucana CD, Mansfield PF, Hicklin DJ, Ellis LM: Induction of neuropilin-1 and vascular endothelial growth factor by epidermal growth factor in human gastric cancer cells. Br J Cancer 2003, 88:796-802.
• [14]Parikh AA, Liu WB, Fan F, Stoeltzing O, Reinmuth N, Bruns CJ, Bucana CD, Evans DB, Ellis LM: Expression and regulation of the novel vascular endothelial growth factor receptor neuropilin-1 by epidermal growth factor in human pancreatic carcinoma. Cancer 2003, 98:720-729.
• [15]Parikh AA, Fan F, Liu WB, Ahmad SA, Stoeltzing O, Reinmuth N, Bielenberg D, Bucana CD, Klagsbrun M, Ellis LM: Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis. Am J Pathol 2004, 164:2139-2151.
• [16]Kreuter M, Woelke K, Bieker R, Schliemann C, Steins M, Buechner T, Berdel WE, Mesters RM: Correlation of neuropilin-1 overexpression to survival in acute myeloid leukemia. Leukemia 2006, 20:1950-1954.
• [17]de Paulis A, Prevete N, Fiorentino I, Rossi FW, Staibano S, Montuori N, Ragno P, Longobardi A, Liccardo B, Genovese A, Ribatti D, Walls AF, Marone G: Expression and functions of the vascular endothelial growth factors and their receptors in human basophils. J Immunol 2006, 177:7322-7331.
• [18]Ellis LM: The role of neuropilins in cancer. Mol Cancer Ther 2006, 5:1099-1107.
• [19]Latil A, Bieche I, Pesche S, Valeri A, Fournier G, Cussenot O, Lidereau R: VEGF overexpression in clinically localized prostate tumors and neuropilin-1 overexpression in metastatic forms. Int J Cancer 2000, 89:167-171.
• [20]Madri JA: Modeling the neurovascular niche: implications for recovery from CNS injury. J Physiol Pharmacol 2009, 60:95-104.
• [21]Meyerson HJ, Blidaru G, Edinger A, Osei E, Schweitzer K, Fu P, Ho L: NRP-1/CD304 expression in acute leukemia: a potential marker for minimal residual disease detection in precursor B-cell acute lymphoblastic leukemia. Am J Clin Pathol 2012, 137:39-50.
• [22]Li X, Tang T, Lu X, Zhou H, Huang Y: RNA interference targeting NRP-1 inhibits human glioma cell proliferation and enhances cell apoptosis. Mol Med Rep 2011, 4:1261-1266.
• [23]Xu J, Xia J: NRP-1 silencing suppresses hepatocellular carcinoma cell growth in vitro and in vivo. Exp Ther Med 2013, 5:150-154.
• [24]Hansel DE, Wilentz RE, Yeo CJ, Schulick RD, Montgomery E, Maitra A: Expression of neuropilin-1 in high-grade dysplasia, invasive cancer, and metastases of the human gastrointestinal tract. Am J Surg Pathol 2004, 28:347-356.
• [25]Baba T, Kariya M, Higuchi T, Mandai M, Matsumura N, Kondoh E, Miyanishi M, Fukuhara K, Takakura K, Fujii S: Neuropilin-1 promotes unlimited growth of ovarian cancer by evading contact inhibition. Gynecol Oncol 2007, 105:703-711.
• [26]Stephenson JM, Banerjee S, Saxena NK, Cherian R, Banerjee SK: Neuropilin-1 is differentially expressed in myoepithelial cells and vascular smooth muscle cells in preneoplastic and neoplastic human breast: a possible marker for the progression of breast cancer. Int J Cancer 2002, 101:409-414.
• [27]Kamiya T, Kawakami T, Abe Y, Nishi M, Onoda N, Miyazaki N, Oida Y, Yamazaki H, Ueyama Y, Nakamura M: The preserved expression of neuropilin (NRP) 1 contributes to a better prognosis in colon cancer. Oncol Rep 2006, 15:369-373.