Systematic profiling of mitochondria-related transcriptome in tumorigenesis, prognosis, and tumor immune microenvironment of intrahepatic cholangiocarcinoma: a multi-center cohort study

转录组 癌变 队列 肝内胆管癌 免疫系统 肿瘤微环境 生物 医学 癌症研究 肿瘤科 病理 内科学 基因 癌症 免疫学 遗传学 基因表达
作者
Bo Chen,Mengmeng Lü,Qi‐Wen Chen,Enmin Zou,Zhiyuan Bo,Jiacheng Li,Rui Zhao,Jungang Zhao,Zhengping Yu,Zhentian Liu,Lijun Wu
出处
期刊:Frontiers in Genetics [Frontiers Media]
卷期号:15
标识
DOI:10.3389/fgene.2024.1430885
摘要

Background Mitochondrial dysfunction has been shown to play a critical role in cancer biology. However, its involvement in intrahepatic cholangiocarcinoma (iCCA) remains significantly understudied. Methods RNA sequencing data of 30 pairs of iCCA and paracancerous tissues were collected from the First Affiliated Hospital of Wenzhou Medical University (WMU). The WMU cohort (n = 30) was integrated with public TCGA (n = 30) and GSE107943 (n = 30) datasets to establish a multi-center iCCA cohort. We merged the TCGA and GSE107943 cohorts into an exploration cohort to develop a mitochondria signature for prognosis assessment, and utilized the WMU cohort for external validation. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Hallmarker analyses were used for functional interpretation of iCCA associated mitochondria-related genes (MRGs). In addition, unsupervised clustering was performed to identify mitochondria-based iCCA subtypes with the data of three institutions. Further investigations were conducted to examine the impact of mitochondrial dysfunction on drug responses, alteration of the tumor immune microenvironment, and immune responses. Results Two hundred and sixty-three iCCA-related MRGs were identified to be related to fatty acid metabolism, oxidative phosphorylation, and apoptosis. Through univariate and multivariate Cox, and LASSO analyses, a mitochondria signature with five optimal MRGs was established to evaluate the prognosis of iCCA patients with the AUC values ranged from 0.785 to 0.928 in the exploration cohort. The signature also exhibited satisfactory performance in the WMU cohort with AUC values of 0.817–0.871, and was identified as an independent risk predictor in both cohorts. Additionally, we found that patients with higher mitochondria score with poor prognosis presented lower infiltration levels of CD4 + T-cell, NK cells, and monocytes, and demonstrated higher sensitivity to targeted therapies, including sorafenib. Furthermore, two distant mitochondria-based subtypes were determined, and subtype 2 was associated with shorter survival time and immunosuppressive tumor microenvironment. Finally, the differential protein expression of five key MRGs was verified by Immunohistochemistry. Conclusion We found mitochondrial dysfunction modulates aberrant metabolism, oxidative stress, immune responses, apoptosis, and drug sensitivity in iCCA. A mitochondria signature and two mitochondria-based iCCA subtypes were identified for clinical risk stratification and immunophenotyping.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

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
张雷应助温婉采纳,获得20
刚刚
汉堡包应助Wwt采纳,获得10
1秒前
1秒前
1秒前
Jasmine发布了新的文献求助30
2秒前
miumiu发布了新的文献求助10
2秒前
桐桐应助Rain采纳,获得10
2秒前
彭于晏应助顺心若魔采纳,获得10
3秒前
坚果发布了新的文献求助30
3秒前
上官若男应助qq158014169采纳,获得10
3秒前
3秒前
LIANG发布了新的文献求助10
4秒前
4秒前
猪猪hero发布了新的文献求助10
5秒前
852应助彳亍采纳,获得10
5秒前
6秒前
雪糕发布了新的文献求助10
6秒前
6秒前
JamesPei应助禾风采纳,获得10
6秒前
6秒前
七七完成签到,获得积分10
8秒前
8秒前
8秒前
Zzddslj发布了新的文献求助10
9秒前
Fran07发布了新的文献求助30
10秒前
钻钻发布了新的文献求助50
10秒前
10秒前
李建勋发布了新的文献求助10
10秒前
深情安青应助六块石头采纳,获得10
11秒前
嘟嘟嘟发布了新的文献求助10
11秒前
11秒前
12秒前
miumiu完成签到,获得积分20
12秒前
13秒前
14秒前
fveie完成签到 ,获得积分10
14秒前
Tim完成签到,获得积分10
14秒前
coolplex发布了新的文献求助30
15秒前
张雷举报圆圆求助涉嫌违规
15秒前
15秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 360
热门求助领域 (近24小时)
化学 材料科学 医学 生物 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 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3971333
求助须知:如何正确求助?哪些是违规求助? 3516028
关于积分的说明 11180607
捐赠科研通 3251147
什么是DOI,文献DOI怎么找? 1795693
邀请新用户注册赠送积分活动 875999
科研通“疑难数据库(出版商)”最低求助积分说明 805228