Guo Yuanwei, Luo Weihao, Hu Zheng, Li Jia, Li Xiaojie, Cao Huiqiu, Li Jun, Wen Bo, Zhang Jian, Cheng Hao, Guo Wangyuan, Tan Tan, Luo Dixian
Translational Medicine Institute, National and Local Joint Engineering Laboratory for High-through Molecular Diagnosis Technology, Collaborative Research Center for Post-doctoral Mobile Stations of Central South University, Affiliated The First People's Hospital of Chenzhou, University of South China, 432000 Chenzhou, People's Republic of China.
Center for Clinical Pathology, Affiliated The First People's Hospital of Chenzhou, University of South China, 432000 Chenzhou, People's Republic of China.
Cell Biosci. 2016 Mar 5;6:18. doi: 10.1186/s13578-016-0082-x. eCollection 2016.
Nasopharyngeal 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.
AKR1B10 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.
Taken 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.
鼻咽癌(NPC)是人类最常见的头颈部癌症之一,在中国南方、东南亚和北非发病率很高。由于其症状不具特异性,鼻咽癌的早期诊断非常困难。尽管放疗和化疗有了很大创新,但5年生存率仍不理想。对于鼻咽癌临床诊断而言,迫切需要高敏感性和特异性的预后生物标志物。寻找特定的靶分子对个体化治疗非常重要。醛酮还原酶B10(AKR1B10)与肿瘤发生和肿瘤发展密切相关,然而,其在鼻咽癌组织中的表达水平尚不清楚。
通过免疫组化评估验证了AKR1B10在良性、癌旁鼻咽组织和鼻咽癌组织中的表达水平。AKR1B10在51例良性标本中的42例(82.4%)以及238例癌旁标本中的235例(98.7%)呈阳性表达。该百分比显著高于鼻咽癌组织中的44.5%(133/299)(p<0.01)。通过实时定量RT-PCR检测,90例鼻咽癌组织样本中AKR1B10 mRNA定量水平(0.10±0.21)显著低于15例良性组织样本中的水平(1.03±1.12)(p<0.01)。鼻咽癌中AKR1B10表达水平与T分期、淋巴结转移呈负相关(p<0.05)。我们采用改良的慢病毒介导方法建立了稳定表达AKR1B10的鼻咽癌单克隆细胞CNE-2/AKR1B10和不表达AKR1B10的CNE-2/载体细胞,通过MTT法、流式细胞术发现AKR1B10抑制CNE-2/AKR1B10细胞的增殖,并通过体外划痕试验发现其抑制细胞迁移。
综上所述,我们的数据表明AKR1B10低表达是鼻咽癌的一个独立预后指标,并且AKR1B10可能参与调节鼻咽癌细胞的增殖和迁移。