Screening out molecular pathways and prognostic biomarkers of ultraviolet-mediated melanoma through computational techniques.

IF 2.3 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY International Journal of Biological Markers Pub Date : 2024-06-01 Epub Date: 2024-02-26 DOI:10.1177/03936155241230968
Arju Hossain, Asif Ahsan, Imran Hasan, Sohel, Arif Khan, Pratul Dipta Somadder, Sumaiya Monjur, Sipon Miah, K M Kaderi Kibria, Kawsar Ahmed, Habibur Rahman
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Abstract

Purpose: Ultraviolet radiation causes skin cancer, but the exact mechanism by which it occurs and the most effective methods of intervention to prevent it are yet unknown. For this purpose, our study will use bioinformatics and systems biology approaches to discover potential biomarkers of skin cancer for early diagnosis and prevention of disease with applicable clinical treatments.

Methods: This study compared gene expression and protein levels in ultraviolet-mediated cultured keratinocytes and adjacent normal skin tissue using RNA sequencing data from the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database. Then, pathway analysis was employed with a selection of hub genes from the protein-protein interaction (PPI) network and the survival and expression profiles. Finally, potential clinical biomarkers were validated by receiver operating characteristic (ROC) curve analysis.

Results: We identified 32 shared differentially expressed genes (DEGs) by analyzing three different subsets of the GSE85443 dataset. Skin cancer development is related to the control of several DEGs through cyclin-dependent protein serine/threonine kinase activity, cell cycle regulation, and activation of the NIMA kinase pathways. The cytoHubba plugin in Cytoscape identified 12 hub genes from PPI; among these 3 DEGs, namely, AURKA, CDK4, and PLK1 were significantly associated with survival (P < 0.05) and highly expressed in skin cancer tissues. For validation purposes, ROC curve analysis indicated two biomarkers: AURKA (area under the curve (AUC) value = 0.8) and PLK1 (AUC value = 0.7), which were in an acceptable range.

Conclusions: Further translational research, including clinical experiments, teratogenicity tests, and in-vitro or in-vivo studies, will be performed to evaluate the expression of these identified biomarkers regarding the prognosis of skin cancer patients.

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通过计算技术筛选出紫外线介导的黑色素瘤的分子途径和预后生物标志物。
目的:紫外线辐射会导致皮肤癌,但其发生的确切机制以及预防皮肤癌的最有效干预方法尚不清楚。为此,我们的研究将利用生物信息学和系统生物学方法来发现皮肤癌的潜在生物标志物,以用于早期诊断和预防疾病,并提供适用的临床治疗方法:本研究利用美国国家生物技术信息中心-基因表达总库(NCBI-GEO)数据库中的 RNA 测序数据,比较了紫外线介导培养的角朊细胞和邻近正常皮肤组织的基因表达和蛋白质水平。然后,利用从蛋白质-蛋白质相互作用(PPI)网络中选择的枢纽基因以及存活和表达谱进行通路分析。最后,通过接收者操作特征曲线(ROC)分析验证了潜在的临床生物标志物:通过分析 GSE85443 数据集的三个不同子集,我们发现了 32 个共有的差异表达基因(DEGs)。皮肤癌的发生与通过依赖细胞周期蛋白丝氨酸/苏氨酸激酶活性、细胞周期调控和激活 NIMA 激酶通路控制多个 DEGs 有关。Cytoscape中的cytoHubba插件从PPI中发现了12个枢纽基因;其中3个DEGs,即AURKA、CDK4和PLK1与生存显著相关(P AURKA(曲线下面积(AUC)值=0.8)和PLK1(AUC值=0.7),处于可接受范围:将开展进一步的转化研究,包括临床实验、致畸性测试、体外或体内研究,以评估这些已确定的生物标志物在皮肤癌患者预后方面的表达情况。
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来源期刊
International Journal of Biological Markers
International Journal of Biological Markers 医学-生物工程与应用微生物
CiteScore
4.10
自引率
0.00%
发文量
43
期刊介绍: IJBM is an international, online only, peer-reviewed Journal, which publishes original research and critical reviews primarily focused on cancer biomarkers. IJBM targets advanced topics regarding the application of biomarkers in oncology and is dedicated to solid tumors in adult subjects. The clinical scenarios of interests are screening and early diagnosis of cancer, prognostic assessment, prediction of the response to and monitoring of treatment.
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