Low expression of Aldo–keto reductase 1B10 is a novel independent prognostic indicator for nasopharyngeal carcinoma

Abstract

BackgroundNasopharyngeal carcinoma (NPC) is one of the most common human head and neck cancers with high incidence in Southern China, Southeast Asia and North Africa. Because of its nonspecific symptoms, the early diagnosis of NPC is very difficult. The 5-year survival rate is not ideal in spite of great innovations in radiation and chemotherapy treatments. Highly sensitive and specific prognostic biomarkers are eager for NPC clinical diagnosis. To find specific target molecules is very important for individualized treatment. Aldo–keto reductase B10 (AKR1B10) is closely related to tumorigenesis and tumor development, and however, its expression level in NPC tissues is not clear.ResultsAKR1B10 expression levels were validated in benign, para-cancerous nasopharyngeal and NPC tissues by immunohistochemical evaluation. AKR1B10 was positively expressed in 42 (82.4 %) of 51 benign specimens, and 235 (98.7 %) of 238 para-carcinoma specimens. This percentage was significantly higher than 44.5 % (133/299) in nasopharyngeal carcinoma tissue (p < 0.01). AKR1B10 mRNA quantitative levels detected by real-time quantitative RT-PCR in 90 NPC tissue samples (0.10 ± 0.21) were significantly lower than that in 15 benign tissue samples (1.03 ± 1.12) (p < 0.01). AKR1B10 expression levels in NPC were correlated negatively with T-classification, lymph node metastasis (p < 0.05). We established nasopharyngeal cancer monoclonal cells CNE-2/AKR1B10 with AKR1B10 stable expression and CNE-2/vector cells without AKR1B10 expression by using a modified lentivirus-mediated method, and found that AKR1B10 inhibited the proliferation of CNE-2/AKR1B10 cells by using MTT assay and flow cytometry, and cell migration by in vitro scratch test.ConclusionTaken together, our data suggest that low expression of AKR1B10 is an independent prognostic indicator in nasopharyngeal carcinoma, and that AKR1B10 may be involved in regulating the proliferation and migration of nasopharyngeal cancer cells.

Opposing roles of the aldo-keto reductases AKR1B1 and AKR1B10 in colorectal cancer

“…The role of AKR1B10 in metastasis appears to be highly context dependent. In breast cancer, AKR1B10 has been reported to be significantly associated with metastasis [39] through upregulation of integrin α5 and δ-catenin [40] whereas, similar to our data, AKR1B10 overexpression in a nasopharyngeal carcinoma-derived cell line was found to result in a slower proliferation and a slower migration [41]. These differences may, at least partly, be explained by the different cell types Fig.…”

“…The prognostic significances of AKR1B1 and AKR1B10 individually have been reported for several different tumor types [15,41,[45][46][47]. In CRC we found that the expression of AKR1B1 was not altered in cancer cells compared to normal cells, both in silico and in in vitro experiments.…”

Expression of AKR1B10 as an independent marker for poor prognosis in human oral squamous cell carcinoma

“…In NPC tissues, AKR1B10 expression seemed high specifically in SCC, but low in basal cell carcinoma, adenoid cystic carcinoma, adenocarcinoma, and undifferentiated carcinoma. However, Guo et al reported that AKR1B10 protein levels were reduced in most of the NPCs compared with paracarcinoma and benign tissues. The frequency of AKR1B10 positivity was significantly higher in patients with differentiated NPC than that in patients with undifferentiated NPC.…”

“…The overexpression of AKR1B10 has been shown to be associated with poor prognosis among patients with breast, cervical, and liver cancers. By contrast, AKR1B10 expression has been reported as an independent variable of favorable prognosis in 3 studies of colorectal, gastric, and nasopharyngeal carcinomas . It is of interests to note that He et al found AKR1B10 expression levels are higher in nasopharyngeal carcinoma (NPC) tissues compared with the normal nasopharyngeal tissues.…”

“…By contrast, AKR1B10 expression has been reported as an independent variable of favorable prognosis in 3 studies of colorectal, gastric, and nasopharyngeal carcinomas. 18,19,38 It is of interests to note that He et al 17 found AKR1B10 expression levels are higher in nasopharyngeal carcinoma (NPC) tissues compared with the normal nasopharyngeal tissues. In NPC tissues, AKR1B10 expression seemed high specifically in SCC, but low in basal cell carcinoma, adenoid cystic carcinoma, adenocarcinoma, and undifferentiated carcinoma.…”