Yang Zixi, Ling Feng, Ruan Sibei, Hu Jiajia, Tang Mingxi, Sun Xingwang, Long Wenbo
Pathology Department of the First Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
Cancer Manag Res. 2021 Nov 23;13:8755-8765. doi: 10.2147/CMAR.S336213. eCollection 2021.
Genetic alterations, including , and promoter mutations (-mu, -mu, -mu, respectively), 1p/19q co-deletion (1p/19q-codel), and promoter methylation (-M), are correlated with glioma tumor development. Therefore, these genetic alterations could serve as biomarkers for the diagnosis, prognosis, and classification of gliomas, combined with the immunohistochemical markers Ki-67 and p53. However, the correlation between these alterations and the expression of Ki-67 and p53 is poorly understood.
We analyzed the prevalence and prognosis of these five alterations, as well as Ki-67 and p53 expression, in 103 primary grade II-IV gliomas via fluorescence qPCR, Sanger sequencing, fluorescence in situ hybridization, and immunohistochemistry.
In the 103 cases, -M was the most common alteration (70.9%), followed by mu (58.3%), mu (46.6%), 1p/19q-codel (34.0%), and -mu (5.8%). No cases showed quintuple-positive alterations, but 26 cases (25.2%) showed quadruple-positive alterations (-mu/-mu/-M/1p/19q-codel). The percentage of -mu and 1p/19q-codel cases decreased with p53 expression, and the percentage of -mu and 1p/19q-codel cases decreased with Ki-67 expression. -mu, -M, and 1p/19q-codel were positive factors for survival rates in glioma patients, while -mu, p53, and Ki-67 positivity were negative factors. Old age, histological grade IV, -mu, 1p/19q-codel, Ki-67+, and p53+/Ki-67+ were significantly correlated with overall survival (OS). However, only p53+/Ki-67+ was an independent prognostic factor for OS in the multivariate Cox-model analysis.
mu only and quadruple-positivity were associated with good OS in glioma patients, while -mu only, -mu/-M and p53+/Ki-67+ were associated with poor prognosis. Combining these genomic alterations and Ki-67/p53 expression should have clinical value in gliomas.
基因改变，包括 、 及 启动子突变（分别为 -mu、-mu、-mu）、1p/19q 共缺失（1p/19q-codel）以及 启动子甲基化（-M），均与胶质瘤的肿瘤发生相关。因此，这些基因改变可作为胶质瘤诊断、预后及分类的生物标志物，并结合免疫组化标志物 Ki-67 和 p53。然而，这些改变与 Ki-67 和 p53 表达之间的相关性尚不清楚。
我们通过荧光定量 PCR、桑格测序、荧光原位杂交及免疫组化分析了 103 例原发性 II-IV 级胶质瘤中这五种改变以及 Ki-67 和 p53 表达的发生率及预后情况。
在 103 例病例中，-M 是最常见的改变（70.9%），其次是 mu（58.3%）、mu（46.6%）、1p/19q-codel（34.0%）和 -mu（5.8%）。无病例显示五项均为阳性的改变，但 26 例（25.2%）显示四项阳性改变（-mu/-mu/-M/1p/19q-codel）。-mu 和 1p/19q-codel 病例的百分比随 p53 表达降低，-mu 和 1p/19q-codel 病例的百分比随 Ki-67 表达降低。-mu、-M 和 1p/19q-codel 是胶质瘤患者生存率的阳性因素，而 -mu、p53 和 Ki-67 阳性是阴性因素。年龄较大、组织学分级为 IV 级、-mu、1p/19q-codel、Ki-67+和 p53+/Ki-67+与总生存期（OS）显著相关。然而，在多变量 Cox 模型分析中，只有 p53+/Ki-67+是 OS 的独立预后因素。
仅 mu 及四项阳性与胶质瘤患者良好的 OS 相关，而仅 -mu、-mu/-M 和 p53+/Ki-67+与预后不良相关。将这些基因组改变与 Ki-67/p53 表达相结合在胶质瘤中应具有临床价值。
