文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

鉴定与 T 细胞耗竭相关的基因,并构建预测肺腺癌免疫治疗反应的预后标志物。

The identification of genes associated T-cell exhaustion and construction of prognostic signature to predict immunotherapy response in lung adenocarcinoma.

机构信息

Department of Medical Oncology, Fujian Medical University Union Hospital, No. 29 Xinquan Street, Fuzhou, 350000, Fujian, China.

Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Jin'an District, Fuzhou, 350000, Fujian, China.

出版信息

Sci Rep. 2023 Aug 17;13(1):13415. doi: 10.1038/s41598-023-40662-z.


DOI:10.1038/s41598-023-40662-z
PMID:37592010
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10435542/
Abstract

T-cell exhaustion (Tex) is considered to be a reason for immunotherapy resistance and poor prognosis in lung adenocarcinoma. Therefore, we used weighted correlation network analysis to identify Tex-related genes in the cancer genome atlas (TCGA). Unsupervised clustering approach based on Tex-related genes divided patients into cluster 1 and cluster 2. Then, we utilized random forest and the least absolute shrinkage and selection operator to identify nine key genes to construct a riskscore. Patients were classified as low or high-risk groups. The multivariate cox analysis showed the riskscore was an independent prognostic factor in TCGA and GSE72094 cohorts. Moreover, patients in cluster 2 with high riskscore had the worst prognosis. The immune response prediction analysis showed the low-risk group had higher immune, stromal, estimate scores, higher immunophenscore (IPS), and lower tumor immune dysfunction and exclusion score which suggested a better response to immune checkpoint inhibitors (ICIs) therapy in the low-risk group. In the meantime, we included two independent immunotherapy cohorts that also confirmed a better response to ICIs treatment in the low-risk group. Besides, we discovered differences in chemotherapy and targeted drug sensitivity between two groups. Finally, a nomogram was built to facilitate clinical decision making.

摘要

T 细胞耗竭(Tex)被认为是肺腺癌免疫治疗耐药和预后不良的原因。因此,我们使用加权相关网络分析(weighted correlation network analysis)在癌症基因组图谱(TCGA)中识别与 Tex 相关的基因。基于与 Tex 相关的基因的无监督聚类方法(unsupervised clustering approach)将患者分为聚类 1 和聚类 2。然后,我们利用随机森林(random forest)和最小绝对收缩和选择算子(least absolute shrinkage and selection operator)来识别九个关键基因,构建风险评分(riskscore)。患者被分为低风险或高风险组。多变量 Cox 分析表明,风险评分是 TCGA 和 GSE72094 队列中的独立预后因素。此外,风险评分高的聚类 2 患者预后最差。免疫反应预测分析表明,低风险组具有更高的免疫、基质、估计评分(estimate scores),更高的免疫表型评分(immunophenscore,IPS),以及更低的肿瘤免疫功能障碍和排斥评分(tumor immune dysfunction and exclusion score),这表明低风险组对免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)治疗的反应更好。同时,我们纳入了两个独立的免疫治疗队列,也证实了低风险组对 ICI 治疗的反应更好。此外,我们发现两组之间在化疗和靶向药物敏感性方面存在差异。最后,构建了一个列线图(nomogram),以方便临床决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/919004ca1571/41598_2023_40662_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/d3acb3c99735/41598_2023_40662_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/dafcdef566f2/41598_2023_40662_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/47e68b72eaff/41598_2023_40662_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/054eab7f7413/41598_2023_40662_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/b0bdf6eda336/41598_2023_40662_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/637a7c33b45a/41598_2023_40662_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/919004ca1571/41598_2023_40662_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/d3acb3c99735/41598_2023_40662_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/dafcdef566f2/41598_2023_40662_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/47e68b72eaff/41598_2023_40662_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/054eab7f7413/41598_2023_40662_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/b0bdf6eda336/41598_2023_40662_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/637a7c33b45a/41598_2023_40662_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a7/10435542/919004ca1571/41598_2023_40662_Fig8_HTML.jpg

相似文献

[1]
The identification of genes associated T-cell exhaustion and construction of prognostic signature to predict immunotherapy response in lung adenocarcinoma.

Sci Rep. 2023-8-17

[2]
Combination of tumor mutation burden and immune infiltrates for the prognosis of lung adenocarcinoma.

Int Immunopharmacol. 2021-9

[3]
Identification of immune activation-related gene signature for predicting prognosis and immunotherapy efficacy in lung adenocarcinoma.

Front Immunol. 2023

[4]
Molecular subtypes of lung adenocarcinoma patients for prognosis and therapeutic response prediction with machine learning on 13 programmed cell death patterns.

J Cancer Res Clin Oncol. 2023-10

[5]
Construction and validation of a prognostic model for lung adenocarcinoma based on endoplasmic reticulum stress-related genes.

Sci Rep. 2022-11-18

[6]
Development and validation of polyamines metabolism-associated gene signatures to predict prognosis and immunotherapy response in lung adenocarcinoma.

Front Immunol. 2023

[7]
Clinical Significance and Immunologic Landscape of a Five-IL(R)-Based Signature in Lung Adenocarcinoma.

Front Immunol. 2021

[8]
Development of a copper metabolism-related gene signature in lung adenocarcinoma.

Front Immunol. 2022

[9]
Prognostic Prediction Value and Biological Functions of Non-Apoptotic Regulated Cell Death Genes in Lung Adenocarcinoma.

Chin Med Sci J. 2023-9

[10]
Identification of Hypoxia-Related Subtypes, Establishment of Prognostic Models, and Characteristics of Tumor Microenvironment Infiltration in Colon Cancer.

Front Genet. 2022-6-17

引用本文的文献

[1]
Integrative bulk RNA analysis unveils immune evasion mechanisms and predictive biomarkers of osimertinib resistance in non-small cell lung cancer.

Discov Oncol. 2025-8-12

[2]
AI-Driven Analysis Unveils Functional Dynamics of Müller Cells in Retinal Autoimmune Inflammation.

bioRxiv. 2025-5-12

[3]
Translating premalignant biology to accelerate non-small-cell lung cancer interception.

Nat Rev Cancer. 2025-5

[4]
The Impact of Genetic Mutations on the Efficacy of Immunotherapies in Lung Cancer.

Int J Mol Sci. 2024-11-7

[5]
Alternative Strategies for Delivering Immunotherapeutics Targeting the PD-1/PD-L1 Immune Checkpoint in Cancer.

Pharmaceutics. 2024-9-7

[6]
Identification of a novel ADCC-related gene signature for predicting the prognosis and therapy response in lung adenocarcinoma.

Inflamm Res. 2024-5

[7]
In-depth analysis of immune cell landscapes reveals differences between lung adenocarcinoma and lung squamous cell carcinoma.

Front Oncol. 2024-1-25

本文引用的文献

[1]
GJB3 promotes pancreatic cancer liver metastasis by enhancing the polarization and survival of neutrophil.

Front Immunol. 2022

[2]
JNK Signaling Promotes Bladder Cancer Immune Escape by Regulating METTL3-Mediated m6A Modification of PD-L1 mRNA.

Cancer Res. 2022-5-3

[3]
Dexamethasone suppresses immune evasion by inducing GR/STAT3 mediated downregulation of PD-L1 and IDO1 pathways.

Oncogene. 2021-8

[4]
Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4 T Cell Responsiveness.

Nutrients. 2021-4-28

[5]
Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy.

Cancers (Basel). 2020-12-11

[6]
Tumor-associated macrophages induce PD-L1 expression in gastric cancer cells through IL-6 and TNF-ɑ signaling.

Exp Cell Res. 2020-11-15

[7]
Metabolic and epigenetic regulation of T-cell exhaustion.

Nat Metab. 2020-9-21

[8]
Study and analysis of antitumor resistance mechanism of PD1/PD-L1 immune checkpoint blocker.

Cancer Med. 2020-11

[9]
The updated landscape of tumor microenvironment and drug repurposing.

Signal Transduct Target Ther. 2020-8-25

[10]
The nuclear oncoprotein Fra-1: a transcription factor knocking on therapeutic applications' door.

Oncogene. 2020-5-8

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索