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干扰素调节因子1介导的免疫细胞浸润与结肠腺癌转移相关。

IRF1-mediated immune cell infiltration is associated with metastasis in colon adenocarcinoma.

作者信息

Shao Yao-Jian, Ni Jun-Jie, Wei Shen-Yu, Weng Xiong-Peng, Shen Meng-Die, Jia Yi-Xin, Meng Li-Na

机构信息

First College of Clinical Medical, Zhejiang Chinese Medical University, Hangzhou.

Second College of Clinical Medical, Wenzhou Medical University, Wenzhou.

出版信息

Medicine (Baltimore). 2020 Sep 11;99(37):e22170. doi: 10.1097/MD.0000000000022170.

Abstract

BACKGROUND

Evidence suggests that metastasis is chiefly responsible for the poor prognosis of colon adenocarcinoma (COAD). The tumor microenvironment plays a vital role in regulating this biological process. However, the mechanisms involved remain unclear. The aim of this study was to identify crucial metastasis-related biomarkers in the tumor microenvironment and investigate its association with tumor-infiltrating immune cells.

METHODS

We obtained gene expression profiles and clinical information from The Cancer Genome Atlas database. According to the "Estimation of STromal and Immune cells in MAlignant Tumor tissue using Expression data" algorithm, each sample generated the immune and stromal scores. Following correlation analysis, the metastasis-related gene was identified in The Cancer Genome Atlas database and validated in the GSE40967 dataset from Gene Expression Omnibus. The correlation between metastasis-related gene and infiltrating immune cells was assessed using the Tumor IMmune Estimation Resource database.

RESULTS

The analysis included 332 patients; the metastatic COAD samples showed a low immune score. Correlation analysis results showed that interferon regulatory factor 1 (IRF1) was associated with tumor stage, lymph node metastasis, and distant metastasis. Furthermore, significant associations between IRF1 and CD8+ T cells, T cell (general), dendritic cells, T-helper 1 cells, and T cell exhaustion were demonstrated by Spearmans correlation coefficients and P values.

CONCLUSIONS

The present findings suggest that IRF1 is associated with metastasis and the degree of immune infiltration of CD8+ T cells (general), dendritic cells, T-helper 1 cells, and T cell exhaustion in COAD. These results may provide information for immunotherapy in colon cancer.

摘要

背景

有证据表明,转移是结肠腺癌(COAD)预后不良的主要原因。肿瘤微环境在调节这一生物学过程中起着至关重要的作用。然而,其中涉及的机制仍不清楚。本研究的目的是在肿瘤微环境中鉴定关键的转移相关生物标志物,并研究其与肿瘤浸润免疫细胞的关系。

方法

我们从癌症基因组图谱数据库中获取了基因表达谱和临床信息。根据“利用表达数据估计恶性肿瘤组织中的基质和免疫细胞”算法,每个样本生成免疫和基质评分。经过相关性分析,在癌症基因组图谱数据库中鉴定出转移相关基因,并在基因表达综合数据库的GSE40967数据集中进行验证。使用肿瘤免疫估计资源数据库评估转移相关基因与浸润免疫细胞之间的相关性。

结果

分析纳入332例患者;转移性COAD样本的免疫评分较低。相关性分析结果表明,干扰素调节因子1(IRF1)与肿瘤分期、淋巴结转移和远处转移相关。此外,通过斯皮尔曼相关系数和P值证明了IRF1与CD8 + T细胞、T细胞(总体)、树突状细胞、辅助性T1细胞和T细胞耗竭之间存在显著相关性。

结论

目前的研究结果表明,IRF1与COAD中的转移以及CD8 + T细胞(总体)、树突状细胞、辅助性T1细胞的免疫浸润程度和T细胞耗竭相关。这些结果可能为结肠癌的免疫治疗提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf81/7489583/3e89e221d550/medi-99-e22170-g002.jpg

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