title: Expression of protease-activated receptor-2 (PAR-2) in patients with nasopharyngeal carcinoma: correlation with clinicopathological features and prognosis.
abstract: We aimed at determining whether the expression of protease-activated receptor 2 (PAR-2) is involved in the progression of nasopharyngeal carcinoma (NPC) and correlated with latent membrane protein 1 (LMP-1), matrix metalloproteinases-9 (MMP9), and angiogenesis of tumor. PAR-2, LMP-1, and MMP9 expressions were detected in 57 biopsies of primary NPC by immunohistochemistry. The presence of Epstein-Barr virus (EBV) was determined using EBER in situ hybridization, and intratumoral microvessels were highlighted by staining endothelial cells for anti-CD34. The correlations with immunostainings and clinicopathological factors, as well as the follow-up data of patients, were analyzed statistically. Strong expression of PAR-2 in 61.4% (35/57) of the biopsies was correlated with extensive lymph node metastasis and advanced stage of NPC. The patients with PAR-2/LMP-1 or PAR-2/MMP9 dual high-expression tumors had a significant worse prognosis than those with single protein high expression and dual low or negative expression tumors (P=0.013 and 0.004, respectively). Angiogenesis in the tumor is related to overall survival of NPC patients (P=0.001), and exhibits strong PAR-2 expression or LMP-1 expression in tumors associated with increased intratumoral microvessel density (P=0.026 and 0.006, respectively). PAR-2 is a possible mediator cooperating with LMP-1 and MMP9 to influence the progression of NPC by inducing angiogenesis and promoting lymph node metastasis.
authors.affiliation: Department of Pathology, 1st Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. lizhi@mail.sysu.edu.cn
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Bian
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Liang
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Liang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D002681:China / Q000453:epidemiology; D003598:Cytoskeletal Proteins; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D060588:LIM Domain Proteins; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C484380:PDLIM7 protein, human; D016601:RNA-Binding Proteins; D044464:Receptor, PAR-2; D012269:Ribosomal Proteins; C067169:RPL22 protein, human; D007633:Keratins; D020780:Matrix Metalloproteinase 9