Vlasenkova Ramilia, Konysheva Daliya, Nurgalieva Alsina, Kiyamova Ramziya
Biomarker Research Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia.
Diagnostics (Basel). 2023 Sep 29;13(19):3092. doi: 10.3390/diagnostics13193092.
The main goal of this study was to characterize cancer/testis antigens (CTAs) as potential molecular markers of ovarian cancer. First, we gathered and analyzed a significantly large dataset of 21 selected CTAs that are encoded by 32 genes; the dataset consisted of the mutation data, expression data, and survival data of patients with ovarian cancer (n = 15,665). The 19 functionally significant missense mutations were identified in 9 CTA genes: ACRBP, CCT4, KDM5B, MAGEA1, MAGEA4, PIWIL1, PIWIL2, PRAME, and SPA17. The analysis of the mRNA expression levels of 21 CTAs in healthy and tumor ovarian tissue showed an up-regulation in the expression level of AKAP3, MAGEA4, PIWIL1, and PRAME in tumor samples and a down-regulation in the expression level of CTAG1A, CTAG1B, MAGEC1, and PIWIL2. The CCT4 up-regulation and PRAME mutations were correlated with a good prognosis for ovarian cancer, while higher levels of GAGE2A and CT45A1 mRNAs were correlated with a poor prognosis for ovarian cancer patients. Thus, GAGE2, CT45, CCT4, and PRAME cancer/testis antigens can be considered as potential prognostic markers for ovarian tumors, and GAGE2, CCT4, and PRAME were revealed to be correlated with the prognosis for ovarian cancer patients for the first time.
本研究的主要目标是将癌/睾丸抗原（CTA）鉴定为卵巢癌潜在的分子标志物。首先，我们收集并分析了一个由32个基因编码的21种选定CTA组成的显著大型数据集；该数据集包含卵巢癌患者（n = 15,665）的突变数据、表达数据和生存数据。在9个CTA基因中鉴定出19个功能显著的错义突变：ACRBP、CCT4、KDM5B、MAGEA1、MAGEA4、PIWIL1、PIWIL2、PRAME和SPA17。对健康和肿瘤卵巢组织中21种CTA的mRNA表达水平分析显示，肿瘤样本中AKAP3、MAGEA4、PIWIL1和PRAME的表达水平上调，而CTAG1A、CTAG1B、MAGEC1和PIWIL2的表达水平下调。CCT4上调和PRAME突变与卵巢癌的良好预后相关，而较高水平的GAGE2A和CT45A1 mRNA与卵巢癌患者的不良预后相关。因此，GAGE2、CT45、CCT4和PRAME癌/睾丸抗原可被视为卵巢肿瘤潜在的预后标志物，并且首次发现GAGE2、CCT4和PRAME与卵巢癌患者的预后相关。
