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鉴定结直肠癌循环肿瘤细胞中的关键基因和通路。

Identification of Key Genes and Pathways Involved in Circulating Tumor Cells in Colorectal Cancer.

机构信息

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Minimally Invasive Surgery Center, Shanghai 200025, China.

Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

出版信息

Anal Cell Pathol (Amst). 2022 Jan 27;2022:9943571. doi: 10.1155/2022/9943571. eCollection 2022.

Abstract

BACKGROUND

Characterization of the features associated with circulating tumor cells (CTCs) is one of major interests for predicting clinical outcome of colorectal cancer (CRC) patients. However, the molecular features of CTCs remain largely unclear.

METHODS

For identification of key genes and pathways, GSE31023, contained CTCs from six metastatic CRC patients and three controls, was retrieved for differentially expressed gene (DEG) analysis. Protein-protein interaction networks of DEGs were constructed. Hub genes from the network were prognostic analyzed, as well as the association with tumor-infiltrating immune cells.

RESULTS

1353 DEGs were identified between the CTC and control groups, with 403 genes upregulated and 950 downregulated. 32 pathways were significantly enriched in KEGG, with ribosome pathway as top. The top 10 hub genes were included, including eukaryotic translation elongation factor 2 (EEF2), ribosomal protein S2 (RPS2), ribosomal protein S5 (RPS5), ribosomal protein L3 (RPL3), ribosomal protein S3 (RPS3), ribosomal protein S14 (RPS14), ribosomal protein SA (RPSA), eukaryotic translation elongation factor 1 alpha 1 (EEF1A1), ribosomal protein S15a (RPS15A), and ribosomal protein L4 (RPL4). The correlation between CD4 T cells and RPS14 (correlation = -0.5) was the highest in colon cancer while CD8 T and RPS2 (correlation = -0.53) was the highest in rectal cancer.

CONCLUSION

This study identified potential role of ribosome pathway in CTC, providing further insightful therapeutic targets and biomarkers for CRC.

摘要

背景

鉴定与循环肿瘤细胞(CTC)相关的特征是预测结直肠癌(CRC)患者临床结局的主要关注点之一。然而,CTC 的分子特征在很大程度上仍不清楚。

方法

为了鉴定关键基因和通路,我们检索了包含 6 名转移性 CRC 患者和 3 名对照的 GSE31023,进行差异表达基因(DEG)分析。构建 DEG 的蛋白质-蛋白质相互作用网络。对网络中的枢纽基因进行预后分析,并与肿瘤浸润免疫细胞进行关联分析。

结果

在 CTC 和对照组之间鉴定出 1353 个 DEG,其中 403 个基因上调,950 个基因下调。KEGG 中有 32 个通路显著富集,核糖体途径为最显著。前 10 个枢纽基因包括真核翻译延伸因子 2(EEF2)、核糖体蛋白 S2(RPS2)、核糖体蛋白 S5(RPS5)、核糖体蛋白 L3(RPL3)、核糖体蛋白 S3(RPS3)、核糖体蛋白 S14(RPS14)、核糖体蛋白 SA(RPSA)、真核翻译延伸因子 1 阿尔法 1(EEF1A1)、核糖体蛋白 S15a(RPS15A)和核糖体蛋白 L4(RPL4)。在结肠癌中,CD4 T 细胞与 RPS14 之间的相关性最高(相关性=-0.5),而在直肠癌中,CD8 T 细胞与 RPS2 之间的相关性最高(相关性=-0.53)。

结论

本研究鉴定了核糖体途径在 CTC 中的潜在作用,为 CRC 提供了进一步的治疗靶点和生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cd2/8813301/de31335857ba/ACP2022-9943571.001.jpg

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