间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题，原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
基于整合分析的晚期胃癌患者预后免疫细胞浸润模型的识别与验证
英文原题：Integrative analysis-based identification and validation of a prognostic immune cell infiltration-based model for patients with advanced gastric cancer.
查看英文原题
Integrative analysis-based identification and validation of a prognostic immune cell infiltration-based model for patients with advanced gastric cancer.
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研究概要
晚期 GC 患者根据瘤内 ICI 程度被成功分为不同聚类，并开发并验证了基于 6 个 ICI 风险基因的预后评估模型。
研究思路结论见上方概要
背景
晚期胃癌（GC）由于高度异质性以及GC肿瘤内免疫细胞浸润（ICI）水平低，仍然难以进行个体化预后评估。因此，本研究旨在开发一种能够根据肿瘤ICI程度对GC患者进行分类并评估预后的模型。
方法
从GSE15459、GSE57303和GSE62254数据集中评估GC患者的ICI程度，并采用无监督聚类方法利用这些值对患者进行分组，随后通过Cox和LASSO回归分析识别ICI聚类相关基因与预后的关联。随后通过对GC肿瘤组织样本进行免疫组化染色验证主要风险基因。
结果
570 例患者被聚类为三个簇，并识别出 289 个 ICI 簇相关基因。构建了一个基于六个关键 ICI 风险基因（CXCL11、RBPMS2、LOC400043、JCHAIN、CT83 和 ORM1）表达的预后模型。根据该模型被判定为高风险的患者，与其他患者相比具有更差的临床特征和生存结局。研究发现，辅助干预对表达高水平 RBPMS2、JCHAIN 或 ORM1 的患者更为有益。此外，在 CMU 队列中验证了，在 GC 肿瘤组织中表达低水平 JCHAIN 或 CT83 的患者表现出显著更好的预后。
展开英文摘要原文
METHODS
The degree of ICI in GC patients from the GSE15459, GSE57303, and GSE62254 datasets were estimated, and these values were used to group patients via an unsupervised clustering approach, after which ICI cluster-related genes were identified the association with prognosis through Cox and LASSO regression analyses. The primary risk genes were then verified by immunohistochemical staining of GC tumor tissue samples.
RESULTS
570 patients were clustered into three clusters and 289 ICI cluster-related genes were identified. A prognostic model based on the expression of six crucial ICI risk genes (CXCL11, RBPMS2, LOC400043, JCHAIN, CT83, and ORM1) wa constructed. Patients identified as being high risk based upon the model have poorer clinical features and survival outcomes compared to the other patients. Adjuvant intervention was found to be more beneficial for patients expressing high levels of RBPMS2, JCHAIN, or ORM1. Furthermore, patients expressing low levels of JCHAIN or CT83 in GC tumor tissues were verified to exhibit a significantly better prognosis in a CMU cohort.
CONCLUSION
Advanced GC patients were successfully grouped into clusters based on the degree of intratumoral ICI, and a prognostic evaluation model based on 6 ICI risk genes was developed and validated.
论文信息
- 作者
- Pan S、Gao Q、Chen Q、Liu P、Tan Y、Liu F、Xu H
- 第一作者单位
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China; Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China.China
- 通讯作者单位
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China; Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China. Electronic address: xuhuimian@126.com.China
- 期刊
- International immunopharmacology2021 Dec
- 原文标识
- PubMed 34678693 · DOI 10.1016/j.intimp.2021.108258