导致卵巢癌顺铂耐药的显着错误表达基因指标尚未完全了解。似乎有几个调控基因和信号通路与化疗耐药表型的出现有关。这里，采用荟萃分析方法来评估参与一线化疗（顺铂）后复发的失调基因。 ，从 GEO 存储库中收集了 6 个卵巢癌库。分别使用 R 中的 SVA 和 ggplot2 软件包进行批量效应消除和质量评估以及箱线图和 PCA。使用 LIMMA R 软件包中的线性回归模型将顺铂耐药和敏感的卵巢癌组与具有显着表达变化的基因进行比较。 DEG 的显着性阈值为 adj p 值 < .05 和 - 1 > logFC > 1。总共鉴定出 261 个基因在顺铂耐药组和顺铂敏感组中具有显着差异表达水平。在前10个上调和下调基因中，PITX2、SNCA和EPHA7（上调）以及TMEM98（下调）是PI3K/AKT信号通路的间接上游调节因子，对化疗耐药的发展做出了巨大贡献通过促进细胞增殖、存活和细胞周期进程以及抑制细胞凋亡来治疗癌症。此外，对DEG的全面评估显示，不仅膜离子通道KCa1.1、Kv4和CACNB4失调，影响细胞兴奋性、增殖和凋亡，而且细胞粘附蛋白COL4A6、EPHA3和CD9也失调，影响正常细胞的附着。细胞 ECM 和细胞凋亡，为逆转顺铂耐药性提供了良好的选择。我们的结果预测并表明 PI3K/AKT 信号通路、离子通道和细胞粘附蛋白的上游调节因子在卵巢癌顺铂耐药性发展中发挥重要作用。© 2023作者。由 Wiley periodicals LLC 出版的癌症报告。

Significant miss-expressed gene indicators contributing to cisplatin resistance in ovarian cancer have not been completely understood. It seems that several regulatory genes and signaling pathways are associated with the emergence of the chemo-resistant phenotype.Here, a meta-analysis approach was adopted to assess deregulated genes involved in relapse after the first line of chemotherapy (cisplatin).To do so, six ovarian cancer libraries were gathered from GEO repository. Batch effect removal and quality assessment, and boxplots and PCA were performed using SVA and ggplot2 packages in R, respectively. Cisplatin-resistant and -sensitive ovarian cancer groups were compared with find genes with significant expression changes using linear regression models in the LIMMA R package. The significance threshold for DEGs was taken as adj p-value < .05 and - 1 > logFC > 1. A total of 261 genes were identified to have significant differential expression levels in the cisplatin-resistant versus cisplatin-sensitive group. Among the 10 top up-regulated and down-regulated genes, PITX2, SNCA, and EPHA7 (up), as well as TMEM98 (down) are indirect upstream regulators of PI3K/AKT signaling pathway, contributing greatly to the development of chemo-resistance in cancer via promoting cell proliferation, survival, and cell cycle progression as well as inhibiting apoptosis. Moreover, a comprehensive assessment of DEGs revealed the dysregulation of not only membrane ion channels KCa1.1, Kv4, and CACNB4, affecting cell excitability, proliferation, and apoptosis but also cell adhesion proteins COL4A6, EPHA3, and CD9, affecting the attachment of normal cells to ECM and apoptosis, introducing good options to reverse cisplatin resistance.Our results predict and suggest that upstream regulators of PI3K/AKT signaling pathway, ion channels, and cell adhesion proteins play important roles in cisplatin resistance development in ovarian cancer.© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.