背景:翻译控制的肿瘤蛋白(TCTP)是一种在多种癌症中升高的多功能蛋白。然而,关于其在口腔癌变和预后中的作用的研究很少。我们最近报道了其互动伙伴的角色,MCL1,在口腔癌进展和结果中。因此,本研究旨在评估TCTP在口腔肿瘤发生中的表达及其与患者单用和联合MCL1预后的关系.
方法:通过免疫组织化学和免疫印迹法评估口腔组织和细胞中TCTP的表达,分别。通过四唑盐测定法分析siRNA/双氢青蒿素处理后的细胞活力。细胞存活,TCTP敲低后的侵袭和致瘤潜力通过克隆形成来评估,Matrigel和软琼脂分析,分别。通过Kaplan-Meier和Cox回归分析TCTP与患者预后的相关性。
结果:TCTP在口腔癌前病变中显著过表达(p<0.0001),口腔肿瘤(p<0.0001)和口腔发育不良和癌细胞与正常口腔粘膜以及复发性(p<0.05)与非复发性口腔肿瘤。Further,TCTP升高与无复发生存率(RFS)和总生存率(OS;风险比=2.29;p<0.05)显著相关.有趣的是,TCTP和MCL1的高共表达进一步降低了RFS(p<0.05)和OS(p<0.05;风险比=3.49;p<0.05)。此外,TCTP敲低降低生存率(p<0.05),侵袭(p<0.01)和体外致瘤潜力(p<0.0001)。双氢青蒿素治疗降低了TCTP水平和口腔癌细胞的活力。
结论:我们的研究表明TCTP在口腔癌进展和不良预后中具有致癌作用。因此,TCTP可能是口腔癌的潜在预后标志物和治疗靶点。
BACKGROUND: Translationally controlled tumour protein (TCTP) is a multifunctional protein elevated in multiple cancers. However, studies on its role in oral carcinogenesis and prognosis are rare. We recently reported the role of its interacting partner, MCL1, in oral cancer progression and outcome. Hence, the present study aimed to assess TCTP expression in oral tumorigenesis and its association with patient outcomes alone and in combination with MCL1.
METHODS: TCTP expression was assessed by immunohistochemistry and immunoblotting in oral tissues and cells, respectively. Cell viability post siRNA/dihydroartemisinin treatment was analysed by tetrazolium salt assay. Cell survival, invasion and tumorigenic potential post TCTP knockdown were assessed by clonogenic, Matrigel and soft-agar assays, respectively. The association of TCTP with patient outcome was analysed by Kaplan-Meier and Cox regression.
RESULTS: TCTP was significantly overexpressed in oral premalignant lesions (p < 0.0001), oral tumours (p < 0.0001) and oral dysplastic and cancer cells versus normal oral mucosa and also in recurrent (p < 0.05) versus non-recurrent oral tumours. Further, elevated TCTP was significantly (p < 0.05) associated with poor recurrence free survival (RFS) and poor overall survival (OS; hazard ratio = 2.29; p < 0.05). Intriguingly, the high co-expression of TCTP and MCL1 further reduced the RFS (p < 0.05) and OS (p < 0.05; hazard-ratio = 3.49; p < 0.05). Additionally, TCTP knockdown decreased survival (p < 0.05), invasion (p < 0.01) and in vitro tumorigenic potential (p < 0.0001). Dihydroartemisinin treatment reduced TCTP levels and viability of oral cancer cells.
CONCLUSIONS: Our studies demonstrate an oncogenic role of TCTP in oral cancer progression and poor outcome. Thus, TCTP may be a potential prognostic marker and therapeutic target in oral cancers.