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应用机器学习方法鉴定与感染相关的生物标志物用于胃肠道肿瘤的诊断

Identification of biomarkers related to infection for the diagnosis of gastrointestinal tumors applying machine learning methods.

作者信息

Ge Tingting, Wang Wei, Zhang Dandan, Le Xubo, Shi Lumei

机构信息

Department of Clinical Laboratory, Beilun People's Hospital, Ningbo, 315800, China.

出版信息

Heliyon. 2024 Nov 16;10(23):e40491. doi: 10.1016/j.heliyon.2024.e40491. eCollection 2024 Dec 15.

Abstract

BACKGROUND

(. ) is a part of normal gastrointestinal microbiota but it could also cause human gastrointestinal diseases. Understanding the mechanism of . in the progression of gastrointestinal tumors can provide novel prevention and treatment strategies for gastrointestinal tumors.

METHODS

The infection score was calculated by single sample GSEA (ssGSEA). Weighted correlation network analysis (WGCNA) and differentially expressed genes (DEGs) analysis were used to identify genes related to infection in gastrointestinal tumors. Hub genes were selected by machine learning methods to establish a diagnostic model. The diagnostic performance of the model was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC) and validated in three external datasets. After determining the biomarkers, immune infiltration analysis and GSEA were further performed. The mRNA expressions of the biomarkers in stomach adenocarcinoma (STAD) cells and the invasion and migration of the tumor cells were detected by conducting experiments.

RESULTS

The . infection score was lower in tumor samples than in normal samples. Eight hub genes were selected from a total of 28 genes associated with -related dysbiosis in gastrointestinal tumors to establish an accurate diagnostic model. The AUC values of and were all greater than 0.7 in three external datasets and the mRNA expression pattern was consistent with TCGA cohort, therefore and were selected as the diagnostic biomarkers. and exhibited significant positive correlations with most immune cells, and inflammation-related pathways were activated in the high expression groups of and . Moreover, was high-expressed but was low-expressed in STAD cells, and silencing suppressed the invasion and migration of STAD cells.

CONCLUSIONS

Overall, we identified and validated 8 robust genes related to applying bioinformatics and machine learning algorithms, providing theoretical foundations for the relationship between -related dysbiosis and gastrointestinal tumors.

摘要

背景

(.)是正常胃肠道微生物群的一部分,但也可能导致人类胃肠道疾病。了解(.)在胃肠道肿瘤进展中的机制可为胃肠道肿瘤提供新的预防和治疗策略。

方法

通过单样本基因集富集分析(ssGSEA)计算(.)感染评分。采用加权基因共表达网络分析(WGCNA)和差异表达基因(DEG)分析来鉴定胃肠道肿瘤中与(.)感染相关的基因。通过机器学习方法选择枢纽基因以建立诊断模型。通过受试者工作特征(ROC)曲线下面积(AUC)评估模型的诊断性能,并在三个外部数据集中进行验证。确定生物标志物后,进一步进行免疫浸润分析和基因集富集分析(GSEA)。通过进行(.)实验检测生物标志物在胃腺癌(STAD)细胞中的mRNA表达以及肿瘤细胞的侵袭和迁移。

结果

肿瘤样本中的(.)感染评分低于正常样本。从与胃肠道肿瘤中(.)相关的生态失调相关的总共28个基因中选择了8个枢纽基因,以建立准确的诊断模型。在三个外部数据集中,(.)和(.)的AUC值均大于0.7,且mRNA表达模式与TCGA队列一致,因此选择(.)和(.)作为诊断生物标志物。(.)和(.)与大多数免疫细胞呈显著正相关,并且在(.)和(.)的高表达组中炎症相关通路被激活。此外,(.)在STAD细胞中高表达而(.)低表达,并且沉默(.)可抑制STAD细胞的侵袭和迁移。

结论

总体而言,我们应用生物信息学和机器学习算法鉴定并验证了8个与(.)相关的可靠基因,为(.)相关的生态失调与胃肠道肿瘤之间的关系提供了理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1ac/11626023/060055a38b03/gr1.jpg

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