Prognostic predictive modeling of non-small cell lung cancer associated with cadmium-related pathogenic genes

IF 2.6 4区 生物学 Q2 BIOLOGY Computational Biology and Chemistry Pub Date : 2024-05-20 DOI:10.1016/j.compbiolchem.2024.108096
Kejian Shi , Chao Shen , Yaxuan Xie , Liangying Fu , Shihan Zhang , Kai Wang , Shafaq Naeem , Zhanpeng Yuan
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Abstract

Persistent exposure to low-dose of cadmium is strongly linked to both the development and prognosis of non-small cell lung cancer (NSCLC), yet the precise molecular mechanism behind this relationship remains uncertain. In this study, cadmium-related pathogenic genes (CRPGs) in NSCLC were identified via differential expression analysis. NSCLC patient clusters related to CRPGs were constructed through univariate Cox and K-means clustering algorithms. Multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were employed to determine the prognosis. Sixteen CRPGs showed a significant association with NSCLC. We found biological and prognostic differences between patients in clusters A and B. A predictive prognostic risk model for NSCLC revealed that FAM83H, MSMO1, and SNAI1 are central. Hence, the 3 hub genes were named. To further elucidate the role of CRPGs in NSCLC, A549 cells were exposed to CdCl2. The mRNA and protein expression levels of the 3 hub genes and cell invasion were detected. Moreover, 10 μM CdCl2 may increase the protein expression of 3 hub genes and enhance the invasive ability of A549 cells. This risk model may have established a theoretical foundation for investigating the mechanisms, treatment, and prognosis of NSCLC.

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与镉相关致病基因有关的非小细胞肺癌预后预测模型
持续暴露于低剂量镉与非小细胞肺癌(NSCLC)的发病和预后密切相关,但这种关系背后的确切分子机制仍不确定。本研究通过差异表达分析确定了非小细胞肺癌中与镉相关的致病基因(CRPGs)。通过单变量 Cox 和 K-means 聚类算法,构建了与 CRPGs 相关的 NSCLC 患者聚类。多变量Cox和最小绝对缩小和选择算子(LASSO)回归分析用于确定预后。16种CRPG与NSCLC有显著相关性。NSCLC的预测性预后风险模型显示,FAM83H、MSMO1和SNAI1是中心基因。因此,这三个中心基因被命名为FAM83H、MSMO1和SNAI1。为进一步阐明CRPGs在NSCLC中的作用,A549细胞暴露于氯化镉。检测了3个中心基因的mRNA和蛋白表达水平以及细胞侵袭情况。此外,10 μM CdCl2可增加3个枢纽基因的蛋白表达,增强A549细胞的侵袭能力。该风险模型为研究NSCLC的发病机制、治疗和预后奠定了理论基础。
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来源期刊
Computational Biology and Chemistry
Computational Biology and Chemistry 生物-计算机:跨学科应用
CiteScore
6.10
自引率
3.20%
发文量
142
审稿时长
24 days
期刊介绍: Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered. Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered. Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.
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