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基于六个免疫相关基因的结直肠癌预后标志物的鉴定与验证

Identification and validation of a prognostic signature based on six immune-related genes for colorectal cancer.

作者信息

Zheng Lifeng, Xu Ziyu, Zhang Wulou, Lin Hao, Zhang Yepeng, Zhou Shu, Liu Zonghang, Gu Xi

机构信息

Department of General Surgery, Nanjing Jiangbei Hospital, Nanjing, Jiangsu, China.

出版信息

Discov Oncol. 2024 May 28;15(1):192. doi: 10.1007/s12672-024-01058-1.

DOI:10.1007/s12672-024-01058-1
PMID:38806963
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11133253/
Abstract

BACKGROUND

Colorectal cancer (CRC) is a prevalent malignancy with high mortality and morbidity rates. Although the significant efficacy of immunotherapy is well established, it is only beneficial for a limited number of individuals with CRC.

METHODS

Differentially expressed immune-related genes (DE-IRGs) were retrieved from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ImmPort databases. A prognostic signature comprising DE-IRGs was developed using univariate, LASSO, and multivariate Cox regression analyses. A nomogram integrating the independent prognostic factors was also developed. CIBERSORT was used to assess immune cell infiltration (ICI). Furthermore, wound-healing, colony formation, migration, and invasion assays were performed to study the involvement of ACTG1 in CRC.

RESULTS

A signature including six DE-IRGs was developed. The overall survival (OS) rate was accurately estimated for TCGA and GSE38832 cohorts. The risk score (RS) of the signature was an independent factor for OS. Moreover, a nomogram encompassing age, RS, and pathological T stage accurately predicted the long-term OS probability of individuals with CRC. The high-risk group had an elevated proportion of patients treated with ICIs, including native B cells, relative to the low-risk group. Additionally, ACTG1 expression was upregulated, which supported the proliferation, migration, and invasion abilities of CRC cells.

CONCLUSIONS

An immune-related prognostic signature was developed for predicting OS and for determining the immune status of individuals with CRC. The present study provides new insights into accurate immunotherapy for individuals with CRC. Moreover, ACTG1 may serve as a new immune biomarker.

摘要

背景

结直肠癌(CRC)是一种常见的恶性肿瘤,死亡率和发病率都很高。尽管免疫疗法的显著疗效已得到充分证实,但它仅对有限数量的CRC患者有益。

方法

从癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)和免疫数据库(ImmPort)中检索差异表达的免疫相关基因(DE-IRG)。使用单变量、LASSO和多变量Cox回归分析开发了一个包含DE-IRG的预后特征。还开发了一个整合独立预后因素的列线图。使用CIBERSORT评估免疫细胞浸润(ICI)。此外,进行了伤口愈合、集落形成、迁移和侵袭试验,以研究ACTG1在CRC中的作用。

结果

开发了一个包含六个DE-IRG的特征。准确估计了TCGA和GSE38832队列的总生存率(OS)。该特征的风险评分(RS)是OS的独立因素。此外,一个包含年龄、RS和病理T分期的列线图准确预测了CRC患者的长期OS概率。相对于低风险组,高风险组接受免疫检查点抑制剂(ICI)治疗的患者比例升高,包括天然B细胞。此外,ACTG1表达上调,这支持了CRC细胞的增殖、迁移和侵袭能力。

结论

开发了一种免疫相关的预后特征,用于预测OS和确定CRC患者的免疫状态。本研究为CRC患者的精准免疫治疗提供了新的见解。此外,ACTG1可能作为一种新的免疫生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/f0b513576f3f/12672_2024_1058_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/1f3dbce917fa/12672_2024_1058_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/85ae44aa7b98/12672_2024_1058_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/ff7d1a38aa50/12672_2024_1058_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/cc5283ec9768/12672_2024_1058_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/ee1cde93a966/12672_2024_1058_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/6589ad732e29/12672_2024_1058_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/55d3fcbed470/12672_2024_1058_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/fcd0971cb611/12672_2024_1058_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/f0b513576f3f/12672_2024_1058_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/1f3dbce917fa/12672_2024_1058_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/85ae44aa7b98/12672_2024_1058_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/ff7d1a38aa50/12672_2024_1058_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/cc5283ec9768/12672_2024_1058_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/ee1cde93a966/12672_2024_1058_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/6589ad732e29/12672_2024_1058_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/55d3fcbed470/12672_2024_1058_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/fcd0971cb611/12672_2024_1058_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2626/11133253/f0b513576f3f/12672_2024_1058_Fig9_HTML.jpg

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