J Cancer 2019; 10(22):5460-5468. doi:10.7150/jca.35362

Research Paper

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

Yaqian Han1, Qianjin Liao1, Heran Wang1, Shan Rao1, Pin Yi1,2, Lu Tang1,2, Yutong Tian1,2, Linda Oyang1, Hui Wang1, Yingrui Shi1✉, Yujuan Zhou1✉

1. Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China.
2. University of South China, Hengyang, 421001, Hunan, China.

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Citation:
Han Y, Liao Q, Wang H, Rao S, Yi P, Tang L, Tian Y, Oyang L, Wang H, Shi Y, Zhou Y. High expression of calreticulin indicates poor prognosis and modulates cell migration and invasion via activating Stat3 in nasopharyngeal carcinoma. J Cancer 2019; 10(22):5460-5468. doi:10.7150/jca.35362. Available from http://www.jcancer.org/v10p5460.htm

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Abstract

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.

Keywords: nasopharyngeal carcinoma, calreticulin, prognosis, progression, STAT3