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沙门氏菌 AvrA 感染对结肠癌的影响:一项计算机模拟研究。

The Effect of Salmonella AvrA Infection on Colon Cancer: An in-silico Study.

机构信息

Doctoral Program, Faculty of Medicine, Universitas Brawijaya, Indonesia.

Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Indonesia.

出版信息

Asian Pac J Cancer Prev. 2023 Jan 1;24(1):163-170. doi: 10.31557/APJCP.2023.24.1.163.

Abstract

OBJECTIVE

Colorectal cancer (CRC) is one of the main causes of morbidity and mortality due to cancer. The purpose of this in-silico study was to examine the relationship of chronic infection mechanisms caused by Salmonella Anti virulence agent A (AvrA) to gene mutations in the carcinogenic process of CRC.

METHODS

Gene expression data on the mouse colon was obtained from the GSE22215 dataset | Gene Expression Omnibus (GEO). Adjusted p-value was calculated using Benjamini & Hochberg False Discovery Rate (FDR<0.01). Gene expression in colon adenocarcicoma tumors was obtained from The Cancer Genome Atlas's (TCGA) Genomic Data Commons (GDC) dataset containing 458 colon tumor samples.

RESULT

Expressions of MLH1, MSH2, EPCAM, APC, and PMS2 in cases of colon adenocarcinoma tumor showed a correlation with genes that underwent changes due to Salmonella AvrA infection. Among the gens of interest, EPCAM was the gene that had the highest correlation compared to other genes (MLH1, MSH2, APC, and PMS2) (n= 514, Gene r-p value < 0.01 =22355). There were 514 genes that had a correlation with cases of AvrA infection. Tumor Necrosis Factor (TNF), which is a gene that is upregulated in AvrA infection and correlates negatively with EPCAM, had the highest BC value compared to other gens (p= 0.0000768). Survival probability showed that EPCAM was highly expressed and it can increase survival time. In addition to TNF, our study indicated that IL1B (p= 0.000419), S100A8 (p= 2.02E-05), S100A9 (p=0.000419) correlated with the gene of interest.

CONCLUSION

Late Salmonella AvrA infection affects the expression of genes involved in inflammation in colorectal cancer samples.

摘要

目的

结直肠癌(CRC)是导致癌症发病率和死亡率的主要原因之一。本研究的目的是探讨沙门氏菌抗毒剂 A(AvrA)引起的慢性感染机制与 CRC 致癌过程中基因突变的关系。

方法

从基因表达综合数据库(GEO)中获得了关于小鼠结肠的基因表达数据 GSE22215 数据集。使用 Benjamini 和 Hochberg 错误发现率(FDR<0.01)计算调整后的 p 值。从包含 458 个结肠肿瘤样本的癌症基因组图谱的基因组数据共享(GDC)数据集中获得了结肠癌肿瘤的基因表达。

结果

结直肠腺癌肿瘤病例中 MLH1、MSH2、EPCAM、APC 和 PMS2 的表达与沙门氏菌 AvrA 感染引起的基因变化相关。在感兴趣的基因中,EPCAM 与其他基因(MLH1、MSH2、APC 和 PMS2)相比,与其他基因的相关性最高(n=514,基因 r-p 值<0.01=22355)。有 514 个基因与 AvrA 感染有关。肿瘤坏死因子(TNF)是 AvrA 感染上调且与 EPCAM 呈负相关的基因,与其他基因相比,其 BC 值最高(p=0.0000768)。生存概率表明,EPCAM 高表达可以增加生存时间。除了 TNF,我们的研究还表明,IL1B(p=0.000419)、S100A8(p=2.02E-05)、S100A9(p=0.000419)与目的基因相关。

结论

晚期沙门氏菌 AvrA 感染影响结直肠癌样本中参与炎症的基因表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d50f/10152855/9cf081cd199a/APJCP-24-163-g001.jpg

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