Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan.
Department of Obstetrics and Gynecology, Show Chwan Memorial Hospital, Changhua 500, Taiwan.
Int J Mol Sci. 2023 Jan 19;24(3):2016. doi: 10.3390/ijms24032016.
Ovarian cancer has the highest mortality rate among gynecological cancers, often diagnosed at the late stage and lacking an effective targeted therapy. Although the study of malignant features of cancer, considered to be cancer stem cells (CSCs), is emerging, the aim of this study was to predict and explore the possible mechanism and clinical value of genetic markers in the development of ovarian cancer from a combined database with CSCs features. The common differentially expressed genes (DEGs) were selected in GSE185833 and GSE176246 datasets from the Gene Expression Omnibus (GEO). The GSE185833 dataset was created to reveal gene expression profiles of peritoneal metastasis tissues using single-cell sequencing, and the GSE176246 dataset was determined from gene expression profiles of chemotherapy-refractory ovarian cancer cell lines compared with ovarian cancer cell lines by RNA-seq analysis. By analyzing the correlation between common DEGs and prognosis of ovarian cancer and its possible pathways and functions were predicted by The Cancer Genome Atlas (TCGA) database. The expression levels of 11 genetic markers were significantly elevated in highly invasive and chemoresistant ovarian cancer. The expression of Actin-like protein 6A (ACTL6A) was found to be correlated with survival prognosis, and the total survival time of the patients with high expression of ACTL6A was shorter than those with low expression. Gene set enrichment analysis (GSEA) showed that ACTL6A positively enriched the gene set of 'Cell cycle' and ACTL6A negatively enriched the gene set of focal adhesion. CP724714, a human epidermal growth factor receptor 2 (HER2) inhibitor, could serve as a therapeutic option when ACTL6A levels are high in ovarian cancer cells. The high expression of ACTL6A is a poor prognostic factor in ovarian cancer and may serve as an effective biomarker for predicting treatment-refractory, metastasis, and prognosis of patients with ovarian cancer. The use of HER2 inhibitors is a promising therapeutic strategy against chemoresistant ovarian cancer.
卵巢癌是妇科癌症中死亡率最高的癌症，通常在晚期诊断，缺乏有效的靶向治疗。尽管对癌症恶性特征的研究，即癌症干细胞（CSC），正在兴起，但本研究的目的是从具有 CSC 特征的联合数据库中预测和探索卵巢癌发展中遗传标记物的可能机制和临床价值。从基因表达综合数据库（GEO）中选择了 GSE185833 和 GSE176246 数据集的常见差异表达基因（DEG）。GSE185833 数据集是使用单细胞测序来揭示腹膜转移组织中基因表达谱的，而 GSE176246 数据集是通过 RNA-seq 分析从卵巢癌细胞系与化疗耐药卵巢癌细胞系的基因表达谱中确定的。通过分析常见 DEG 与卵巢癌预后的相关性，并通过癌症基因组图谱（TCGA）数据库预测其可能的途径和功能。在高度侵袭性和耐药性卵巢癌中，11 个遗传标记物的表达水平显著升高。发现肌动蛋白样蛋白 6A（ACTL6A）的表达与生存预后相关，ACTL6A 高表达患者的总生存时间短于低表达患者。基因集富集分析（GSEA）显示，ACTL6A 正向富集“细胞周期”基因集，ACTL6A 负向富集焦点黏附基因集。当卵巢癌细胞中 ACTL6A 水平较高时，CP724714（一种人表皮生长因子受体 2（HER2）抑制剂）可作为一种治疗选择。ACTL6A 的高表达是卵巢癌的不良预后因素，可能成为预测治疗耐药、转移和卵巢癌患者预后的有效生物标志物。HER2 抑制剂的使用是一种有前途的治疗耐药性卵巢癌的策略。
