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The prognostic value of dynamic serum lactate dehydrogenase (LDH) levels in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) hasn’t been explored. We retrospectively analyzed 1,428 cases of NPC treated with IMRT with or without chemotherapy. Elevated pre- and/or post-treatment LDH levels were found to be associated with unfavorable overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS), but not with local relapse-free survival (LRFS). The dynamic variations in LDH levels were prognostic factors for OS, DFS and DMFS, but not for LRFS. Multivariate analysis revealed that the N category, T category, post-treatment serum LDH level and age were independent prognostic factors for OS. Our results demonstrated that dynamic variations in LDH levels were associated with risk of distant failure and death, which may shed light on the dynamics of the disease and the response to therapy. We consider that LDH measurements will be of great clinical importance in the management of NPC, especially, when considering “decision points” in treatment algorithms. Therefore, we strongly recommend that LDH levels should be determined before and after treatment in NPC patients and the results integrated into decisions regarding treatment strategies.

Clinically, distant metastasis after primary treatment remains a key problem in nasopharyngeal carcinoma (NPC), and the treatment outcome of metastatic NPC remains disappointing, so there is a pressing need to identify novel therapeutic strategies. In accordance with our previous microarray data, we found that miR-101 was downregulated in NPC clinical specimens and cell lines. Ectopic expression of miR-101 significantly suppressed NPC cell migration, invasion and angiogenesis in vitro and inhibited angiogenesis and metastasis in vivo using the chicken chorioallantoic membrane model. Furthermore, ITGA3 was identified and validated as a novel target of miR-101, and the restoration of ITGA3 expression potently rescued the suppressive effects of miR-101. In addition, NPC patients with high ITGA3 expression had poorer overall survival and distant metastasis-free survival than patients with low ITGA3 expression, and ITGA3 overexpression was an independent poor prognostic factor in NPC. More importantly, we demonstrated that the systemic delivery of lentivirus-mediated miR-101 abrogated the lung metastatic colonization formation of NPC cells without obvious toxicity. Our study elucidates the molecular mechanisms of miR-101/ITGA3 pathway in regulating NPC metastasis and angiogenesis, and the systemic delivery of miR-101 provides a potent evidence for the development of a novel microRNA-targeting anticancer strategy for NPC patients.