Primary NPC has unique pathological and clinical characteristics and radiotherapy with or without chemotherapy is the mainstream treatment. Although the 5-year survival of patients with NPC has steadily improved over the past three decades (Lee et al., 2005; Chan, 2011), overall 15-58% of patients experienced recurrence after radical radiotherapy in the era of conventional radiotherapy (Chang et al., 2000), and 13-22% have experienced recurrence in the era of intensity-modulated radiation therapy (Ng et al., 2011; Su et al., 2011). In most patients with recurrence after complete remission following radical radiotherapy, the cancer returns within an average of 1.5 years, with local recurrences accounting for 70% of such cases (Yang et al., 1996; Lee et al., 1999). Recurrent NPC may be local, regional, or distant and is usually treated with radiation therapy and/or chemotherapy and occasionally with surgery. Retreatment for recurrent NPC poses a critical challenge, given its poor efficacy and serious toxicities (Xu et al., 2013). Improved identification of prognostic factors by means of molecular testing may be useful in the diagnosis of diseases and their exact subtypes and may aid physicians in selecting individualized treatment, increasing the likelihood of local salvage. Several prognostic factors have been identified in recent years, including recurrent tumor T stage, histologic type, patient age, and disease-free interval to recurrence. Of these factors, short-term interval to recurrence has been shown to correlate with poor outcome (Chou et al., 2008; Xu et al., 2015). Therefore, identification of molecular markers that may lead to an improved understanding of recurrent NPC and to individualized treatment is imperative.
Consistent with our study results, it has been shown in pancreatic cancer cell lines that upregulation of claudin-4 diminished the invasiveness and the metastatic potential of the cancer cells (Michl et al., 2003). This may be explained by the review held by Ding et al. (2013), who reported that the downregulation of claudins contributes to epithelial transformation by increasing the paracellular permeability of nutrients and growth factors to cancerous cells.
Possible explanation for studies revealing opposite opinion is through the interaction with zona occludens-1 involved in TJs, to affect other cell signaling pathways involved in neoplastic transformation (Resnick et al., 2005). Few other plausible mechanisms have been proposed, one is through the suppression of apoptosis through the increased expression of claudin-1 in NPC cell lines (Lee et al., 2009) and the other is through the activation of matrix metalloproteinase (MMP) proteins (Agarwal et al., 2005; Ku et al., 2006). Upregulation of claudin-1 in oral SCC enhances invasion through the activation of MMP-2 and MMP-1, and overexpression of claudins-3 and 4 in ovarian surface epithelial cell promotes invasion by increasing MMP-2 activity (Agarwal et al., 2005).
Although this study revealed nonsignificant results with TNM stage, it revealed that HPI for MIB-1 protein was associated with poor survival. Small number of cases tested may contribute to this nonsignificance as regards TNM staging.
There are no conflicts of interest.
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