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运用综合生物信息学分析探索宫颈癌和卵巢癌的共同通路及常见生物标志物。

Exploration of the shared pathways and common biomarkers in cervical and ovarian cancer using integrated bioinformatics analysis.

作者信息

Liu Fang, Wang Min, Zhu Tian, Xu Cong, Wang Guangming

机构信息

School of Clinical Medicine, Dali University, Dali, 671000, Yunnan, People's Republic of China.

Center of Genetic Testing, The First Affiliated Hospital of Dali University, Dali, 671000, Yunnan,, People's Republic of China.

出版信息

Discov Oncol. 2024 Dec 23;15(1):826. doi: 10.1007/s12672-024-01725-3.

Abstract

OBJECTIVE

Searching for potential biomarkers and therapeutic targets for early diagnosis of gynecological tumors to improve patient survival.

METHODS

Microarray datasets of cervical cancer (CC) and ovarian cancer (OC) were downloaded from the Gene Expression Omnibus (GEO) database, then, differential gene expression between cancerous and normal tissues in the datasets was analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to screen for co-expression modules associated with CC and OC. The screened shared genes were then further analyzed for functional pathway enrichment. Next, the least absolute shrinkage and selection operator (LASSO) with tenfold cross validation is used to further screened for common diagnostic biomarkers for the two diseases, and further validation is performed using two independent GEO datasets. Finally, the CIBERSORT algorithm was used to estimate the immune infiltration levels of CC and OC, and the correlation between immune cell infiltration and common biomarkers was explored.

RESULTS

After crossing the common DEGs detected by "Limma" R package with the common module genes identified by WGCNA, 44 shared genes were obtained. Functional enrichment indicates that these shared genes are mainly related to DNA synthesis pathways. Lasso regression analysis revealed that EFNA1, TYMS, and WISP2 were co-diagnostic markers for CC and OC, and then based on their expression levels and diagnostic efficacy, EFNA1 was selected as the best co-marker for CC and OC. Immune infiltration analysis shows that the immune environment has a significant impact on the occurrence and development of CC and OC, and the expression of EFNA1 is related to changes in immune cells. Gene-drug interaction analyses identified 27 common drug compounds that interact with candidate genes.

CONCLUSION

This study adopted bioinformatics methods to investigate the common pathways and identify diagnostic markers between CC and OC, suggesting that DNA synthesis and immune environment are closely related to the occurrence and development of CC and OC. EFNA1 may be a potential diagnostic indicator and therapeutic target for patients with CC and OC.

摘要

目的

寻找妇科肿瘤早期诊断的潜在生物标志物和治疗靶点,以提高患者生存率。

方法

从基因表达综合数据库(GEO)下载宫颈癌(CC)和卵巢癌(OC)的微阵列数据集,然后分析数据集中癌组织与正常组织之间的差异基因表达。进行加权基因共表达网络分析(WGCNA)以筛选与CC和OC相关的共表达模块。然后对筛选出的共享基因进行功能通路富集分析。接下来,使用具有十倍交叉验证的最小绝对收缩和选择算子(LASSO)进一步筛选这两种疾病的共同诊断生物标志物,并使用两个独立的GEO数据集进行进一步验证。最后,使用CIBERSORT算法估计CC和OC的免疫浸润水平,并探讨免疫细胞浸润与共同生物标志物之间的相关性。

结果

通过“Limma”R包检测到的常见差异表达基因(DEG)与WGCNA鉴定的共同模块基因交叉后,获得了44个共享基因。功能富集表明这些共享基因主要与DNA合成途径相关。Lasso回归分析显示,EFNA1、TYMS和WISP2是CC和OC的共同诊断标志物,然后根据它们的表达水平和诊断效能,选择EFNA1作为CC和OC的最佳共同标志物。免疫浸润分析表明,免疫环境对CC和OC的发生发展有显著影响,EFNA1的表达与免疫细胞的变化有关。基因-药物相互作用分析确定了27种与候选基因相互作用的常见药物化合物。

结论

本研究采用生物信息学方法研究CC和OC之间的共同途径并鉴定诊断标志物,表明DNA合成和免疫环境与CC和OC的发生发展密切相关。EFNA1可能是CC和OC患者的潜在诊断指标和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edc9/11666853/31e7dbb193f5/12672_2024_1725_Fig1_HTML.jpg

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