Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Department of Biochemistry, All India Institute of Medical Sciences, Bilaspur, India.
Biosci Rep. 2022 Apr 29;42(4). doi: 10.1042/BSR20212685.
Prothymosin-α (PTMA), a nuclear protein, is strikingly associated with unfavorable clinical outcomes in many cancers. However, no information about its clinical relevance in glioma was available. Therefore in the present study, we evaluated the prognostic utility of this protein in a cohort of 81 glioma patients. The PTMA expression was assessed by immunohistochemical analysis, quantitative PCR, and Western blotting. Furthermore, the association of PTMA with clinicopathological features and molecular alterations were assessed in the patient cohort and validated in multiomics datasets, The Cancer Genome Atlas (TCGA; n=667) and Chinese Glioma Genome Atlas (CGGA; n=1013). We observed an increase in PTMA expression with increasing histological grades of this malignancy. PTMA immunostaining also displayed a strong positive association with the MIB-1 index. Univariate analysis revealed a superior prognostic value of PTMA to predict overall survival (OS) as compared with the routinely used markers (p53, isocitrate dehydrogenase (IDH) 1 (IDH1), α-thalassemia/intellectual disability syndrome X-linked (ATRX), and Ki-67). Interestingly, in Cox regression analysis it emerged as an independent predictor of OS (hazard ratio (HR) = 13.71, 95% CI = 5.96-31.52, P<0.0001). Thus, our results demonstrate the potential prognostic utility of PTMA in glioma which may prove useful in the management of this deadly malignancy.
胸腺素 α(PTMA)是一种核蛋白,与许多癌症的不良临床结局显著相关。然而,目前尚无关于其在神经胶质瘤中临床相关性的信息。因此,在本研究中,我们评估了这种蛋白在 81 名神经胶质瘤患者队列中的预后作用。通过免疫组织化学分析、定量 PCR 和 Western blot 评估了 PTMA 的表达。此外,还在患者队列中评估了 PTMA 与临床病理特征和分子改变的相关性,并在多组学数据集,癌症基因组图谱(TCGA;n=667)和中国神经胶质瘤基因组图谱(CGGA;n=1013)中进行了验证。我们观察到随着这种恶性肿瘤组织学分级的增加,PTMA 的表达增加。PTMA 免疫染色也与 MIB-1 指数呈强正相关。单因素分析显示,与常规标志物(p53、异柠檬酸脱氢酶 1(IDH1)、α-地中海贫血/智力发育障碍综合征 X 连锁(ATRX)和 Ki-67)相比,PTMA 对预测总生存期(OS)具有更好的预后价值。有趣的是,在 Cox 回归分析中,它是 OS 的独立预测因子(风险比(HR)=13.71,95%CI=5.96-31.52,P<0.0001)。因此,我们的研究结果表明,PTMA 在神经胶质瘤中具有潜在的预后作用,这可能有助于该致命性恶性肿瘤的治疗。