Programa de Pós-Gradução em Ciências Fisiológicas, Universidade Federal do Rio Grande/FURG, Instituto de Ciências Biológicas, Laboratório de Biologia Molecular, Av. Itália, Km 8, Campus Carreiros, 96203-900 Rio Grande, RS, Brazil.
Universidade Federal do Rio Grande/FURG, Centro de Ciência da Computação (C3), Laboratório de Biologia Computacional, Rodovia, RS-734, s/n, 96203-900 Rio Grande, RS, Brazil.
An Acad Bras Cienc. 2024 Sep 9;96(suppl 1):e20231365. doi: 10.1590/0001-3765202420231365. eCollection 2024.
We aimed to find new therapeutic targets related to Cancer Stem Cell alterations in recurrent patients from two TCGA cohorts: Testicular Germ Cell Tumor (TGCT) and Uterine Corpus Endometrial Carcinoma (UCEC). Raw sequencing data were downloaded from the TCGA database. Datasets containing RNA expression and Methylation files were directly downloaded from cBioportal. Variant Call Format files (VCFs) were downloaded from the GDC portal. Gene enrichment analysis was performed using GSEA (Gene Set Enrichment Analysis) software. Transcriptome profiling, coexpression co-occurrence, networks, and survival analyses were performed using cBioportal tools, while mutational analysis of patients was processed using UNIX scripts. We found that cancer stem cell transcription factors were highly expressed in Testicular Germ Cell Tumor (TGCT) and Uterine Corpus Endometrial Carcinoma (UCEC) cohorts, compared to the other 29 cancer cohorts in TCGA. Patients presented a poorer diagnosis when the genes (POU5F1, NANOG, SOX2, SALL4, ABCB1, ABCC1, and ABCG2) were altered. In UCEC cohorts, recurrent patients showed the ABCG2 potentially phosphorylated by the PIM1 kinase. In the TGCT cohort, genes ABCB1 and ABCG2 only appeared in the phosphonetwork in recurrent patients potentially phosphorylated by the same kinase, PIM1, but also by PRKACA. Our data indicate that PRKACA and PIM1 may modulate POU5F1 phosphorylation.
我们旨在从两个 TCGA 队列（睾丸生殖细胞肿瘤 (TGCT) 和子宫体子宫内膜癌 (UCEC)）的复发性患者中寻找与癌症干细胞改变相关的新治疗靶点。原始测序数据从 TCGA 数据库下载。包含 RNA 表达和甲基化文件的数据集直接从 cBioportal 下载。变体调用格式文件 (VCFs) 从 GDC 门户下载。使用 GSEA（基因集富集分析）软件进行基因富集分析。使用 cBioportal 工具进行转录组谱分析、共表达共现、网络和生存分析，而使用 UNIX 脚本处理患者的突变分析。我们发现与 TCGA 中的其他 29 个癌症队列相比，癌症干细胞转录因子在睾丸生殖细胞肿瘤 (TGCT) 和子宫体子宫内膜癌 (UCEC) 队列中高度表达。当基因（POU5F1、NANOG、SOX2、SALL4、ABCB1、ABCC1 和 ABCG2）发生改变时，患者的诊断较差。在 UCEC 队列中，复发性患者表现出 ABCG2 可能被 PIM1 激酶磷酸化。在 TGCT 队列中，基因 ABCB1 和 ABCG2 仅出现在复发性患者的磷酸化网络中，可能被同一激酶 PIM1 磷酸化，也可能被 PRKACA 磷酸化。我们的数据表明 PRKACA 和 PIM1 可能调节 POU5F1 的磷酸化。
