High expression of calreticulin indicates poor prognosis and modulates cell migration and invasion via activating Stat3 in nasopharyngeal carcinoma

Objective: Emerging evidence suggests that calreticulin (CALR) has great impacts on the tumor formation and progression of various cancers, but the role of CALR remains controversial. We investigated the expression and clinical significance of CALR in nasopharyngeal carcinoma (NPC). Methods: Immunohistochemistry was used to detect the expression of CALR in NPC tissues, and the correlation of CALR with clinicopathological characteristics and prognosis were analyzed. The cell functions of CALR in NPC cells were also performed in vitro. Results: Compared with non-tumor nasopharyngeal epithelium (NPE) tissues, CALR expression was markedly up-regulated in NPC tissues (P < 0.001), and the high expression of CALR was positively associated with advanced clinical stage (P=0.003) and metastasis (P=0.023). Compared to the patients with low expression of CALR, patients who displayed high expression of CALR may achieve a poorer progression-free survival (PFS) and overall survival (OS) (P < 0.001). Furthermore, multivariate analysis showed that high expression of CALR was an independent predictor of poor prognosis. In addition, we found that knockdown of CALR significantly inhibited the proliferation, migration and invasion of CNE2 and HONE1 cells in vitro, and the mechanism might be associated with inactivation of Stat3 signaling pathway. Conclusion: CALR may promote NPC progression and metastasis via involving Stat3 signaling pathway, and can be regarded as an effective potential predictor for progression and prognosis of NPC.