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

膀胱癌肿瘤微环境异质性确定了具有不同生物学特征的亚型,可预测预后和抗 PD-L1 反应。

Tumor microenvironment heterogeneity in bladder cancer identifies biologically distinct subtypes predicting prognosis and anti-PD-L1 responses.

机构信息

Department of Urology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan Province, China.

出版信息

Sci Rep. 2023 Nov 10;13(1):19563. doi: 10.1038/s41598-023-44028-3.


DOI:10.1038/s41598-023-44028-3
PMID:37949863
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10638294/
Abstract

Bladder cancer (BCa) is heterogeneous in the tumour microenvironment (TME). However, the role of the TME in BCa in modulating the response to immunotherapy has not been fully explored. We therefore analysed fractions of immune cells using CIBERSORTx and clustered BCa into subtypes. We also analyzed weighted correlation networks to generate immunotherapy-related hub genes that we used to construct a prediction model using multivariate Cox and LASSO regression analyses. We found that BCa comprised three subtypes (C1‒C3). The prognosis of the patients was the most favourable and the response rate to anti-programmed death ligand 1 (PD-L1) was the highest in C1 among the three subtypes. Immune cells, including CD8, CD4 memory activated, and follicular helper T cells, activated NK cells, and M1 macrophages infiltrated the C1 subtype. The C2 subtype was enriched in M0 macrophages and activated mast cells, and the C3 subtype was enriched in B and resting immune cells. Mechanistically, the enhanced immunogenicity of subtypes C1 and C2 correlated positively with a higher response rate, whereas the dysregulated ECM-related pathways in the C2 subtype and glycolytic and fatty acid metabolic pathways in the C3 subtype impaired the responses of patients to anti-PD-L1 therapy. We also constructed a TME-related signature based on 18 genes that performed well in terms of overall survival. In conclusion, we determined prognoses and anti-PD-L1 responses by analysing TME heterogeneity in BCa.

摘要

膀胱癌(BCa)在肿瘤微环境(TME)中具有异质性。然而,TME 在调节免疫治疗反应中的作用尚未得到充分探索。因此,我们使用 CIBERSORTx 分析了免疫细胞的分数,并将 BCa 聚类为亚型。我们还分析了加权相关网络,以生成与免疫治疗相关的枢纽基因,我们使用多元 Cox 和 LASSO 回归分析构建了一个预测模型。我们发现 BCa 包含三个亚型(C1-C3)。在这三个亚型中,C1 型患者的预后最好,对抗程序性死亡配体 1(PD-L1)的反应率最高。包括 CD8、CD4 记忆激活和滤泡辅助 T 细胞、激活 NK 细胞和 M1 巨噬细胞在内的免疫细胞浸润了 C1 亚型。C2 亚型富含 M0 巨噬细胞和激活的肥大细胞,C3 亚型富含 B 细胞和静止免疫细胞。从机制上讲,C1 和 C2 亚型增强的免疫原性与更高的反应率呈正相关,而 C2 亚型中失调的 ECM 相关途径和 C3 亚型中糖酵解和脂肪酸代谢途径损害了患者对抗 PD-L1 治疗的反应。我们还构建了一个基于 18 个基因的 TME 相关特征,这些基因在总体生存方面表现良好。总之,我们通过分析 BCa 中的 TME 异质性来确定预后和抗 PD-L1 反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/ca21161d1b97/41598_2023_44028_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/bcd3c63aca15/41598_2023_44028_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/bde768850a74/41598_2023_44028_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/1b55560e4b69/41598_2023_44028_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/e1b0127d2276/41598_2023_44028_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/82a837665f7c/41598_2023_44028_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/2a60ec40d4e1/41598_2023_44028_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/7dc469205a3f/41598_2023_44028_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/ca21161d1b97/41598_2023_44028_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/bcd3c63aca15/41598_2023_44028_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/bde768850a74/41598_2023_44028_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/1b55560e4b69/41598_2023_44028_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/e1b0127d2276/41598_2023_44028_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/82a837665f7c/41598_2023_44028_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/2a60ec40d4e1/41598_2023_44028_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/7dc469205a3f/41598_2023_44028_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ad/10638294/ca21161d1b97/41598_2023_44028_Fig8_HTML.jpg

相似文献

[1]
Tumor microenvironment heterogeneity in bladder cancer identifies biologically distinct subtypes predicting prognosis and anti-PD-L1 responses.

Sci Rep. 2023-11-10

[2]
Integration of multi-omics and clinical treatment data reveals bladder cancer therapeutic vulnerability gene combinations and prognostic risks.

Front Immunol. 2023

[3]
Genomic stratification based on microenvironment immune types and PD-L1 for tailoring therapeutic strategies in bladder cancer.

BMC Cancer. 2021-5-31

[4]
Discovery of a T cell proliferation-associated regulator signature correlates with prognosis risk and immunotherapy response in bladder cancer.

Int Urol Nephrol. 2024-11

[5]
Characterization of stem cell landscape and identification of stemness-relevant prognostic gene signature to aid immunotherapy in colorectal cancer.

Stem Cell Res Ther. 2022-6-9

[6]
Immune landscape of distinct subtypes in urothelial carcinoma based on immune gene profile.

Front Immunol. 2022

[7]
Molecular heterogeneity of anti-PD-1/PD-L1 immunotherapy efficacy is correlated with tumor immune microenvironment in East Asian patients with non-small cell lung cancer.

Cancer Biol Med. 2020-8-15

[8]
Targeting WD repeat domain 5 enhances chemosensitivity and inhibits proliferation and programmed death-ligand 1 expression in bladder cancer.

J Exp Clin Cancer Res. 2021-6-21

[9]
Lysine N-methyltransferase SETD7 promotes bladder cancer progression and immune escape via STAT3/PD-L1 cascade.

Int J Biol Sci. 2023

[10]
Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy.

Cancer Med. 2023-2

引用本文的文献

[1]
and as potential biomarkers in bladder cancer: Insights from a comprehensive bioinformatic analysis.

Bladder (San Franc). 2025-4-11

[2]
Key immune cells and their crosstalk in the tumor microenvironment of bladder cancer: insights for innovative therapies.

Explor Target Antitumor Ther. 2025-3-31

[3]
Sarcomatoid areas of urothelial carcinoma are enriched for CD163-positive antigen-presenting cells.

J Pathol Clin Res. 2025-3

[4]
A pan-cancer analysis of the oncogenic role of N-acetyltransferase 8 like in human cancer.

Discov Oncol. 2024-12-18

本文引用的文献

[1]
Inhibiting ACK1-mediated phosphorylation of C-terminal Src kinase counteracts prostate cancer immune checkpoint blockade resistance.

Nat Commun. 2022-11-14

[2]
Harnessing Antitumor CD4 T Cells for Cancer Immunotherapy.

Cancers (Basel). 2022-1-5

[3]
Immune Modulatory Properties of Collagen in Cancer.

Front Immunol. 2021

[4]
Checkpoint Inhibition in Bladder Cancer: Clinical Expectations, Current Evidence, and Proposal of Future Strategies Based on a Tumor-Specific Immunobiological Approach.

Cancers (Basel). 2021-11-29

[5]
Infiltration and Polarization of Tumor-associated Macrophages Predict Prognosis and Therapeutic Benefit in Muscle-Invasive Bladder Cancer.

Cancer Immunol Immunother. 2022-6

[6]
Tumor-Associated Macrophages in Bladder Cancer: Biological Role, Impact on Therapeutic Response and Perspectives for Immunotherapy.

Cancers (Basel). 2021-9-21

[7]
clusterProfiler 4.0: A universal enrichment tool for interpreting omics data.

Innovation (Camb). 2021-7-1

[8]
IOBR: Multi-Omics Immuno-Oncology Biological Research to Decode Tumor Microenvironment and Signatures.

Front Immunol. 2021

[9]
Analysis of Tumor Microenvironment Characteristics in Bladder Cancer: Implications for Immune Checkpoint Inhibitor Therapy.

Front Immunol. 2021

[10]
The Construction and Analysis of Tumor-Infiltrating Immune Cells and ceRNA Networks in Bladder Cancer.

Front Genet. 2020-12-18

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