血清HOTTIP表达在鼻咽癌患者中上调，并预示预后不良。
Serum HOTTIP expression is upregulated in nasopharyngeal carcinoma patients and predicts poor prognosis.
作者信息
Wang Ding-Ting, Luo Jian, Feng Hua-Jun, Wang Yuan-Yuan
机构信息
The Affiliated Hospital of Southwest Medical University, Department of Otolaryngology Head and Neck Surgery, Luzhou, China.
The First People's Hospital of Yibin, Department of Otolaryngology Head and Neck Surgery, Yibin, China.
出版信息
Braz J Otorhinolaryngol. 2025 Jan-Feb;91(1):101471. doi: 10.1016/j.bjorl.2024.101471. Epub 2024 Jul 20.
OBJECTIVE
Nasopharyngeal Carcinoma (NPC) is a tumor with ethnic and geographic distribution characteristics. HOXA Transcript at the distal Tip (HOTTIP) has been confirmed to have cancer-promoting effects in various tumors. The aim of this study was to investigate the clinical significance of HOTTIP in the development of NPC and its role in prognostic assessment.
METHODS
Reverse transcription real-time PCR was used to analyze the expression of HOTTIP in the serum of 122 NPC patients before treatment, 35 controls and 30 NPC patients after treatment, and the relationship between HOTTIP expression and the clinicopathological features and prognosis of NPC patients was analyzed. The NPC cell lines CNE1 and HNE1 stably overexpressing HOTTIP were constructed using the retroviral method. Plate clone formation assays, MTT assays, flow cytometry, and Transwell migration and invasion assays were used to investigate the effects of HOTTIP overexpression on the colony-formation ability, cell proliferation ability, apoptosis, and migration and invasion abilities of CNE1 and HNE1 cells, respectively.
RESULTS
HOTTIP was highly expressed in NPC serum and cells compared with the control group; serum HOTTIP expression in NPC patients after treatment was significantly lower than that before treatment; Kaplan-Meier survival curve revealed that the Progression-Free Survival (PFS) and Overall Survival (OS) of the HOTTIP low-expression group were both better than those of the HOTTIP high-expression group; COX proportional hazard models showed that high HOTTIP expression was an independent risk factor for PFS in NPC patients. The overexpression of HOTTIP promoted the proliferation, migration and invasion abilities of CNE1 and HNE1 NPC cells and inhibited cell apoptosis in vitro cell experiments.
CONCLUSION
Increased HOTTIP expression in serum indicates a poor prognosis and may be used as a molecular marker and therapeutic target in NPC.
目的
鼻咽癌（NPC）是一种具有种族和地理分布特征的肿瘤。远端HOXA转录本（HOTTIP）已被证实在多种肿瘤中具有促癌作用。本研究旨在探讨HOTTIP在鼻咽癌发生发展中的临床意义及其在预后评估中的作用。
方法
采用逆转录实时荧光定量PCR分析122例初治鼻咽癌患者、35例对照者及30例治疗后鼻咽癌患者血清中HOTTIP的表达情况，并分析HOTTIP表达与鼻咽癌患者临床病理特征及预后的关系。采用逆转录病毒法构建稳定过表达HOTTIP的鼻咽癌细胞系CNE1和HNE1。分别采用平板克隆形成实验、MTT实验、流式细胞术及Transwell迁移和侵袭实验，研究HOTTIP过表达对CNE1和HNE1细胞克隆形成能力、细胞增殖能力、凋亡以及迁移和侵袭能力的影响。
结果
与对照组相比，HOTTIP在鼻咽癌血清和细胞中高表达；治疗后鼻咽癌患者血清HOTTIP表达明显低于治疗前；Kaplan-Meier生存曲线显示，HOTTIP低表达组的无进展生存期（PFS）和总生存期（OS）均优于HOTTIP高表达组；COX比例风险模型显示，HOTTIP高表达是鼻咽癌患者PFS的独立危险因素。体外细胞实验表明，HOTTIP过表达促进了CNE1和HNE1鼻咽癌细胞的增殖、迁移和侵袭能力，并抑制了细胞凋亡。
结论
血清中HOTTIP表达升高提示预后不良，可能作为鼻咽癌的分子标志物和治疗靶点。
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