利用综合生物信息框架鉴定卵巢癌的新基因和新途径

IF 3.1 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Hibba Rashid, Asad Ullah, Sajjad Ahmad, Salma Mohammed Aljahdali, Yasir Waheed, Bilal Shaker, Alhanouf I. Al-Harbi, Alhumaidi B. Alabbas, Safar M. Alqahtani, Maaged A. Akiel, Muhammad Irfan
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引用次数: 0

摘要

卵巢癌(OC)是全球妇科癌症相关死亡的重要原因之一,死亡率很高。尽管对卵巢癌发病机制的认识取得了一些进展,但对其发病和预后的分子机制仍然知之甚少。因此,本研究旨在确定参与 OC 发病机制的枢纽基因,以作为选择性诊断和治疗靶点。为此,研究人员使用数据集 GEO2R 来检索差异表达基因。研究共发现五个基因(CDKN1A、DKK1、CYP1B1、NTS 和 GDF15)在 OC 中有差异表达。随后,利用 STRING 数据库进行了网络分析,并利用 Cytoscape 构建了网络。Cytoscape中的网络分析工具预测了276个上调基因和269个下调基因。此外,还进行了 KEGG 分析,以确定与 OC 相关的不同通路。随后,以 p 值 0.05 为临界值,进行了生存分析,以验证基因表达的改变并预测枢纽基因。四个基因(CDKN1A、DKK1、CYP1B1 和 NTS)被预测为重要的枢纽基因,而一个基因(GDF15)被预测为不重要。CDKN1A、DKK1、NTS、GDF15和CYP1B1的上述预测基因的调整P值分别为2.85E - 07、5.49E - 06、4.28E - 07、1.43E - 07和3.70E - 07;此外,在GEO数据集中,上述基因的预测LogFc值分别为6.08、5.76、5.74、5.01和4.9。通过方框图分析,研究人员分析了这些基因在正常细胞和肿瘤细胞中的表达情况。研究发现,三个基因在肿瘤细胞中的表达量较高,而两个基因(CDKN1A 和 DKK1)在正常细胞中的表达量较高。根据 CDKN1A 的方框图分析,50% 的肿瘤细胞介于约 3.8 和 5 之间,而 50%的正常细胞介于约 6.9 和 7.9 之间,高于肿瘤细胞。这表明,根据 GEPIA 方框图,正常细胞中 CYP1B1 的表达水平较高;此外,DKK1 的方框图显示,50% 的肿瘤细胞的表达水平约在 0 至 0.5 之间,低于正常细胞的表达水平,正常细胞的表达水平约在 0.3 至 0.9 之间。这表明 DKK1 在正常基因中高表达。总之,本研究为了解 OC 的分子机制提供了新的视角。所发现的枢纽基因和候选药物靶点有可能成为 OC 患者的替代诊断和治疗方案。我们还需要进一步研究这些发现的临床意义,并开发有效的干预措施来改善 OC 患者的预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of Novel Genes and Pathways of Ovarian Cancer Using a Comprehensive Bioinformatic Framework

Ovarian cancer (OC) is a significant contributor to gynecological cancer-related deaths worldwide, with a high mortality rate. Despite several advances in understanding the pathogenesis of OC, the molecular mechanisms underlying its development and prognosis remain poorly understood. Therefore, the current research study aimed to identify hub genes involved in the pathogenesis of OC that could serve as selective diagnostic and therapeutic targets. To achieve this, the dataset GEO2R was used to retrieve differentially expressed genes. The study identified a total of five genes (CDKN1A, DKK1, CYP1B1, NTS, and GDF15) that were differentially expressed in OC. Subsequently, a network analysis was performed using the STRING database, followed by the construction of a network using Cytoscape. The network analyzer tool in Cytoscape predicted 276 upregulated and 269 downregulated genes. Furthermore, KEGG analysis was conducted to identify different pathways related to OC. Subsequently, survival analysis was performed to validate gene expression alterations and predict hub genes, using a p-value of 0.05 as a threshold. Four genes (CDKN1A, DKK1, CYP1B1, and NTS) were predicted as significant hub genes, while one gene (GDF15) was predicted as non-significant. The adjusted P values of said predicted genes are 2.85E − 07, 5.49E − 06, 4.28E − 07, 1.43E − 07, and 3.70E − 07 for CDKN1A, DKK1, NTS, GDF15, and CYP1B1 respectively; additionally 6.08, 5.76, 5.74, 5.01, and 4.9 LogFc values of the said genes were predicted in GEO data set. In a boxplot analysis, the expression of these genes was analyzed in normal and tumor cells. The study found that three genes were highly expressed in tumor cells, while two genes (CDKN1A and DKK1) were more elevated in normal cells. According to the boxplot analysis for CDKN1A, 50% of tumor cells ranged between approx 3.8 and 5, while 50% of normal cells ranged between approx 6.9 and 7.9, which is greater than tumor cells. This shows that in normal cells, the CYP1B1 has a high expression level according to the GEPIA boxplot; addtionally the boxplot for DKK1 indicated that 50% of tumor cells ranged between approx 0 and 0.5, which was less than that of normal cells which ranged between approx 0.3 and 0.9. It shows that DKK1 is highly expressed in normal genes. Overall, the current study provides novel insights into the molecular mechanisms underlying OC. The identified hub genes and drug candidate targets could potentially serve as alternative diagnostic and therapeutic options for OC patients. Further research is needed to investigate the clinical significance of these findings and develop effective interventions that can improve the prognosis of patients with OC.

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来源期刊
Applied Biochemistry and Biotechnology
Applied Biochemistry and Biotechnology 工程技术-生化与分子生物学
CiteScore
5.70
自引率
6.70%
发文量
460
审稿时长
5.3 months
期刊介绍: This journal is devoted to publishing the highest quality innovative papers in the fields of biochemistry and biotechnology. The typical focus of the journal is to report applications of novel scientific and technological breakthroughs, as well as technological subjects that are still in the proof-of-concept stage. Applied Biochemistry and Biotechnology provides a forum for case studies and practical concepts of biotechnology, utilization, including controls, statistical data analysis, problem descriptions unique to a particular application, and bioprocess economic analyses. The journal publishes reviews deemed of interest to readers, as well as book reviews, meeting and symposia notices, and news items relating to biotechnology in both the industrial and academic communities. In addition, Applied Biochemistry and Biotechnology often publishes lists of patents and publications of special interest to readers.
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