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鉴定和验证 Rab GTPases RAB13 作为结直肠癌患者腹膜转移和免疫细胞浸润的生物标志物。

Identification and validation of Rab GTPases RAB13 as biomarkers for peritoneal metastasis and immune cell infiltration in colorectal cancer patients.

机构信息

Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

Oncology Department III, People's Hospital of Liaoning Province, Shenyang, Liaoning, China.

出版信息

Front Immunol. 2024 Aug 13;15:1403008. doi: 10.3389/fimmu.2024.1403008. eCollection 2024.

Abstract

BACKGROUND

As one of the most common cancer, colorectal cancer (CRC) is with high morbidity and mortality. Peritoneal metastasis (PM) is a fatal state of CRC, and few patients may benefit from traditional therapies. There is a complex interaction between PM and immune cell infiltration. Therefore, we aimed to determine biomarkers associated with colorectal cancer peritoneal metastasis (CRCPM) and their relationship with immune cell infiltration.

METHODS

By informatic analysis, differently expressed genes (DEGs) were selected and hub genes were screened out. RAB13, one of the hub genes, was identificated from public databases and validated in CRC tissues. The ESTIMATE, CEBERSORT and TIMER algorithms were applied to analyze the correlation between RAB13 and immune infiltration in CRC. RAB13's expression in different cells were analyzed at the single-cell level in scRNA-Seq. The Gene Set Enrichment Analysis (GSEA) was performed for RAB13 enrichment and further confirmed. Using oncoPredict algorithm, RAB13's impact on drug sensitivity was evaluated.

RESULTS

High RAB13 expression was identified in public databases and led to a poor prognosis. RAB13 was found to be positively correlated with the macrophages and other immune cells infiltration and from scRNA-Seq, RAB13 was found to be located in CRC cells and macrophages. GSEA revealed that high RAB13 expression enriched in a various of biological signaling, and oncoPredict algorithm showed that RAB13 expression was correlated with paclitaxel sensitivity.

CONCLUSION

Our study indicated clinical role of RAB13 in CRC-PM, suggesting its potential as a therapeutic target in the future.

摘要

背景

作为最常见的癌症之一,结直肠癌(CRC)具有较高的发病率和死亡率。腹膜转移(PM)是 CRC 的致命状态,传统疗法对少数患者可能有效。PM 与免疫细胞浸润之间存在复杂的相互作用。因此,我们旨在确定与结直肠癌腹膜转移(CRCPM)相关的生物标志物及其与免疫细胞浸润的关系。

方法

通过信息学分析,选择差异表达基因(DEGs)并筛选出核心基因。RAB13 是核心基因之一,从公共数据库中鉴定并在 CRC 组织中验证。ESTIMATE、CEBERSORT 和 TIMER 算法用于分析 RAB13 与 CRC 中免疫浸润的相关性。在单细胞水平的 scRNA-Seq 中分析 RAB13 在不同细胞中的表达。进行基因集富集分析(GSEA)以评估 RAB13 的富集情况并进一步验证。使用 oncoPredict 算法评估 RAB13 对药物敏感性的影响。

结果

在公共数据库中发现高 RAB13 表达与预后不良相关。RAB13 与巨噬细胞和其他免疫细胞浸润呈正相关,并且从 scRNA-Seq 中发现 RAB13 位于 CRC 细胞和巨噬细胞中。GSEA 显示高 RAB13 表达富集在各种生物学信号中,而 oncoPredict 算法显示 RAB13 表达与紫杉醇敏感性相关。

结论

我们的研究表明 RAB13 在 CRC-PM 中的临床作用,提示其作为未来治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efc4/11347351/dc438c08ec72/fimmu-15-1403008-g001.jpg

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