Comprehensive single-cell analysis deciphered microenvironmental dynamics and immune regulator olfactomedin 4 in pathogenesis of gallbladder cancer

间质细胞 免疫系统 胆囊癌 胆囊 癌症研究 医学 肿瘤微环境 生物 免疫学 癌症 病理 内科学 遗传学
作者
Huisi He,Shuzhen Chen,Yong Yu,Zhecai Fan,You–Wen Qian,Yaping Dong,Yuting Song,Caiming Zhong,Sun Xiaojuan,Qiqi Cao,Shiyao Li,Weihan Huang,Wenxin Li,Mingzhu Zhuang,Jinxian Yang,Xianming Wang,Jiaqian Wang,Dongfang Wu,Hongyang Wang,Wen Wen
出处
期刊:Gut [BMJ]
卷期号:: gutjnl-331773 被引量:2
标识
DOI:10.1136/gutjnl-2023-331773
摘要

Objective Elucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention. Design We performed single-cell transcriptome analysis on 230 737 cells from 15 GBCs, 4 cholecystitis samples, 3 gallbladder polyps, 5 gallbladder adenomas and 16 adjacent normal tissues. Findings were validated through large-scale histological assays, digital spatial profiler multiplexed immunofluorescence (GeoMx), etc. Further molecular mechanism was demonstrated with in vitro and in vivo studies. Results The cell atlas unveiled an altered immune landscape across different pathological states of gallbladder diseases. GBC featured a more suppressive immune microenvironment with distinct T-cell proliferation patterns and macrophage attributions in different GBC subtypes. Notably, mutual exclusivity between stromal and immune cells was identified and remarkable stromal ecosystem (SC) heterogeneity during GBC progression was unveiled. Specifically, SC1 demonstrated active interaction between Fibro-iCAF and Endo-Tip cells, correlating with poor prognosis. Moreover, epithelium genetic variations within adenocarcinoma (AC) indicated an evolutionary similarity between adenoma and AC. Importantly, our study identified elevated olfactomedin 4 (OLFM4) in epithelial cells as a central player in GBC progression. OLFM4 was related to T-cell malfunction and tumour-associated macrophage infiltration, leading to a worse prognosis in GBC. Further investigations revealed that OLFM4 upregulated programmed death-ligand 1 (PD-L1) expression through the MAPK-AP1 axis, facilitating tumour cell immune evasion. Conclusion These findings offer a valuable resource for understanding the pathogenesis of gallbladder diseases and indicate OLFM4 as a potential biomarker and therapeutic target for GBC.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
丘比特应助仙女的小可爱采纳,获得10
刚刚
sssssxxxx完成签到 ,获得积分10
刚刚
1秒前
2秒前
yuanvv发布了新的文献求助20
2秒前
不懈奋进应助yang采纳,获得30
3秒前
青栞发布了新的文献求助10
4秒前
cach完成签到,获得积分10
5秒前
6秒前
6秒前
Singularity应助GC采纳,获得10
7秒前
8秒前
8秒前
李哥完成签到,获得积分10
8秒前
kkkkk完成签到,获得积分20
9秒前
CodeCraft应助binshier采纳,获得10
10秒前
流光完成签到 ,获得积分10
11秒前
小巧的如冬完成签到 ,获得积分10
12秒前
啊是是是发布了新的文献求助10
12秒前
大智完成签到,获得积分10
12秒前
13秒前
kkkkk发布了新的文献求助10
13秒前
15秒前
科研通AI2S应助Billy采纳,获得10
15秒前
15秒前
毛慢慢发布了新的文献求助10
16秒前
大智发布了新的文献求助10
17秒前
明亮淇完成签到,获得积分10
18秒前
20秒前
爆米花应助可爱半双采纳,获得10
20秒前
20秒前
cannon8发布了新的文献求助10
22秒前
23秒前
24秒前
学习痴完成签到 ,获得积分10
25秒前
沉静青寒完成签到,获得积分10
25秒前
26秒前
泡泡完成签到,获得积分10
27秒前
归雁完成签到,获得积分10
29秒前
大福完成签到,获得积分10
30秒前
高分求助中
Sustainability in Tides Chemistry 2000
The ACS Guide to Scholarly Communication 2000
Studien zur Ideengeschichte der Gesetzgebung 1000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Threaded Harmony: A Sustainable Approach to Fashion 810
Pharmacogenomics: Applications to Patient Care, Third Edition 800
精细有机单元反应合成技术手册,张大国编著,北京:化学工业出版社 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3078917
求助须知:如何正确求助?哪些是违规求助? 2731588
关于积分的说明 7519223
捐赠科研通 2380169
什么是DOI,文献DOI怎么找? 1262147
科研通“疑难数据库(出版商)”最低求助积分说明 611840
版权声明 597396