Overexpression of Semaphorin 3A Is a Marker Associated with Poor Prognosis in Patients with Nasopharyngeal Carcinoma

Abstract

Semaphorins were discovered as guidance signals that mediate neural development. Recent studies suggest that semaphorin 3A (Sema3A), a member of the semaphorin family, is involved in the development of several cancers. This study aimed to analyze the association of Sema3A with the clinical features of nasopharyngeal carcinoma (NPC), an Epstein–Barr virus-associated carcinoma, and the Epstein–Barr virus primary oncogene latent membrane protein 1 (LMP1). The expression of Sema3A and LMP1 was immunohistochemically examined in the 35 NPC specimens. The mean expression scores for Sema3A and LMP1 were 20.8% ± 14.5% and 13.9% ± 14.8%, respectively. The expression of Sema3A significantly correlated with that of LMP1 (r = 0.41, p = 0.014). In addition, the Sema3A high cohort showed significantly poorer prognosis than the Sema3A low cohort. Sema3A expression was higher in the LMP1-positive KH-1 and KR-4 cell lines compared to the LMP1-negative HeLa cells. Overexpression of LMP1 in the LMP1-negative AdAH cell line upregulated Sema3A expression, both at the transcriptional and translational level. Finally, Sema3A expression was associated with poor prognosis in patients with NPC. Our data suggest that LMP1 induces the expression of Sema3A, which may promote tumor progression in NPC.

Special Issue: Epstein–Barr–Virus–Associated Cancers

“…This Special Issue assembles eleven papers, comprising seven research articles, two reviews, and two brief reports, which collectively provide novel information on the mechanisms of oncogenesis [ 2 , 3 , 4 , 5 , 6 ] and viral replication [ 7 , 8 , 9 , 10 ], as well as applications for diagnosis [ 11 , 12 ].…”

“…Using a variety of methods and approaches, several studies have provided a novel notion in understanding how EBV contributes to the development of various tumors, including GC [ 2 , 3 ], HL [ 4 ], NPC [ 5 ], and oral squamous cell carcinoma [ 6 ], on a molecular basis. A distinct feature of EBV-associated GC is the significant infiltration of immune cells in the epithelium, which appears to establish a unique tumor microenvironment.…”

“…Bioinformatic approaches revealed that an EBV-encoded microRNA, miR-BART17-5p, directly downregulates Kruppel-like factor 2 in EBV-associated GC cells, which subsequently confers an oncogenic phenotype [ 3 ]. Other studies identified host factors such as Notch1 and Pax5 or Semaphorin 3A, which exhibited correlated expression with viral infection in EBV-associated HL [ 4 ] or NPC [ 5 ], respectively, indicating that they could be considered as a candidate diagnostic/prognostic marker and a therapeutic target in these tumors. EBV establishes latent infection in squamous cell carcinoma cell lines, suggesting that it can be used as an in vitro model to investigate the role of EBV in the development of uncharacterized oral squamous cell carcinoma [ 6 ].…”