Yang Lin, Li Fengyan, Lei Fangyong, Wang Yan, Wu Shu, Song Libing, Chen Yong
Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
State Key Laboratory of Oncology in Southern China, Guangzhou, China.
Tumour Biol. 2015 Sep;36(10):7977-86. doi: 10.1007/s13277-015-3518-8. Epub 2015 May 12.
Chromosome 14 open reading frame 166 (c14orf166) contributes to regulation of centrosome architecture, transcription initiation, and RNA elongation and processing. However, the role of c14orf166 in human cancer remains unclear. This study aimed to investigate the expression and clinicopathological significance of c14orf166 in nasopharyngeal carcinoma (NPC). Real-time PCR and Western blotting analyses were employed to examine c14orf166 expression in immortalized primary nasopharyngeal epithelial cells (NP69), six NPC cell lines, three paired tumor samples and the adjacent noncancerous tissues from the same patients, and three additional tumor samples. Immunohistochemistry was performed to examine c14orf166 protein expression in archived paraffin-embedded tumor samples from 109 patients with clinicopathologically confirmed NPC. The association of c14orf166 expression with clinicopathological features and survival outcomes was assessed. C14orf166 messenger RNA and protein expression were upregulated in NPC cell lines and human tumor tissues compared to NP69 cells and noncancerous tissue samples, respectively. Immunohistochemical analyses revealed 104/109 (95.4 %) of the NPC tissue samples expressed c14orf166. High expression of c14orf166 (cutoff score >6) was significantly associated with gender (P = 0.016), clinical stage (P = 0.010), T classification (P = 0.013), N classification (P = 0.029), distant metastasis (P < 0.001), vital status (P = 0.001), and treatment method (P = 0.028; chi-square test). High c14orf166 expression was associated with significantly shorter overall survival (OS) and disease-free survival (DFS) than low c14orf166 expression. Multivariate analysis revealed c14orf166 was an independent prognostic indicator of OS and DFS in all patients (P = 0.046, P = 0.006) and was associated with poor OS and DFS in the subgroups with advanced clinical stage (P = 0.037, P = 0.001), lymph node metastasis (P = 0.001, P < 0.001), and T3-T4 disease (P = 0.005, P = 0.001), respectively. C14orf166 is overexpressed and may represent a novel prognostic factor in NPC.
14号染色体开放阅读框166(c14orf166)有助于中心体结构的调节、转录起始以及RNA延伸和加工。然而,c14orf166在人类癌症中的作用仍不清楚。本研究旨在探讨c14orf166在鼻咽癌(NPC)中的表达及临床病理意义。采用实时荧光定量PCR和蛋白质印迹分析检测永生化原代鼻咽上皮细胞(NP69)、6种NPC细胞系、3对肿瘤样本及同一患者的癌旁非癌组织,以及另外3个肿瘤样本中c14orf166的表达。对109例经临床病理确诊为NPC患者的存档石蜡包埋肿瘤样本进行免疫组织化学检测,以检测c14orf166蛋白表达。评估c14orf166表达与临床病理特征及生存结局的相关性。与NP69细胞和非癌组织样本相比,c14orf166信使核糖核酸和蛋白表达在NPC细胞系和人类肿瘤组织中分别上调。免疫组织化学分析显示,109例NPC组织样本中有104例(95.4%)表达c14orf166。c14orf166高表达(截断分数>6)与性别(P = 0.016)、临床分期(P = 0.010)、T分级(P = 0.013)、N分级(P = 0.029)、远处转移(P < 0.001)、生存状态(P = 0.001)和治疗方法(P = 0.028;卡方检验)显著相关。与低c14orf166表达相比,高c14orf166表达与总生存期(OS)和无病生存期(DFS)显著缩短相关。多因素分析显示,c14orf166是所有患者OS和DFS的独立预后指标(P = 0.046,P = 0.006),并且在临床晚期(P = 0.037,P = 0.001)、有淋巴结转移(P = 0.001,P < 0.001)和T3 - T4期疾病(P = 0.005,P = 0.001)的亚组中分别与较差的OS和DFS相关。c14orf166在NPC中过表达,可能是一种新的预后因素。