PXD033206

PXD033206 is an original dataset announced via ProteomeXchange.

Title	Novel Molecular Subgroups of Intrahepatic Cholangiocarcinoma Discovered by Single-Cell RNA Sequencing-Assisted Multi-Omics Analysis
Description	Intrahepatic cholangiocarcinoma (ICC) is a relatively rare but highly aggressive tumour type that responds poorly to chemotherapy and immunotherapy. Comprehensive molecular characterization of ICC is essential for the development of novel therapeutics. Here, we constructed two independent cohorts from two clinic centres. A comprehensive multiomics analysis of ICC via proteomic, whole-exon sequencing (WES) and single-cell RNA sequencing (scRNA-seq) was performed. Novel ICC tumour subtypes were derived in the training cohort (n = 110) using proteomic signatures and their associated activated pathways, which was further validated in the validation cohort (n = 41). Three molecular subtypes, chromatin remodelling, metabolism, and chronic inflammation, with distinct prognoses in ICC were identified. The chronic inflammation subtype was associated with a poor prognosis. Our random forest algorithm revealed that the mutation of KMT2D frequently occurred in the metabolism subtype and was associated with lower inflammatory activity. scRNA-seq further identified an APOE+C1QB+ macrophage subtype, which showed the capacity to reshape the chronic inflammation subtype and contribute to a poor prognosis in ICC. Altogether, with single-cell transcriptome-assisted multiomics analysis, we identified novel molecular subtypes of ICC and validated APOE+C1QB+ TAMs as potential immunotherapy targets against ICC.
HostingRepository	iProX
AnnounceDate	2022-04-13
AnnouncementXML	Submission_2023-03-05_20:03:02.420.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tiannan Guo
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-13 04:51:13	ID requested
1	2022-04-13 04:52:34	announced
⏵ 2	2023-03-05 20:03:03	announced	2023-03-06: Update information.

Shen Y, Xu S, Ye C, Li Q, Chen R, Wu W, Jiang Q, Jia Y, Zhang X, Fan L, Fu W, Jiang M, Chen J, Timko MP, Zhao P, Ruan J, Proteomic and single-cell landscape reveals novel pathogenic mechanisms of HBV-infected intrahepatic cholangiocarcinoma. iScience, 26(2):106003(2023) [pubmed]

submitter keyword: FFPE, ICC, proteomics

Tiannan Guo
contact affiliation	Westlake University
contact email	Tiannan.guo@hotmail.com
lab head
Tiannan Guo
contact affiliation	Westlake University
contact email	Tiannan.guo@hotmail.com
dataset submitter

iProX dataset URI