PXD039045

PXD039045 is an original dataset announced via ProteomeXchange.

Title	A metabolomic and proteomic study to elucidate the molecular mechanisms of immunotherapy resistance in patients with oesophageal squamous cell carcinoma
Description	Systemic chemotherapy, the standard first-line treatment option for patients with advanced oesophageal squamous cell carcinoma (OSCC), results in a median survival of approximately 1 year. Immune checkpoint inhibitors are a breakthrough oncology treatment option; however, most patients with advanced OSCC develop primary and acquired resistance to PD-1 monoclonal antibody, severely affecting their prognosis. Therefore, there is an urgent need to investigate the molecular mechanism underlying resistance to treatment. This study aimed to explore the mechanism of resistance to PD-1 monoclonal antibody. We collected plasma samples from patients with OSCC treated with immunotherapy, who achieved pathological response/partial response (CR/PR) or stable disease/progressive disease (SD/PD) after one treatment cycle. TM widely targeted metabolomics, widely targeted lipidomics, and DIA proteomics assays were performed. Differential metabolites were screened based on fold change (FC) ≥ 1.5 or ≤ 0.67 and a VIP ≥ 1; differential proteins were screened based on FC > 1.5 or < 0.67 and a p-value < 0.05. The identified metabolites were annotated and mapped using the KEGG pathway databases The differential proteins were annotated to the Gene Ontology and KEGG pathway databases. A correlation network diagram was drawn using differential expressed proteins and metabolites with (Pearson correlation coefficient) r > 0.80 and p-value <0.05. We finally screened 197 and 113 differential metabolites and proteins, respectively, in patients with CR/PR and SD/PD groups. The KEGG enrichment analysis revealed that all of these were enriched in cholesterol metabolism and in the NF-κB and phospholipase D signalling pathways. Our study is the first to demonstrate that PD-1 inhibitor resistance may be attributed to cholesterol metabolism or NF-κB and phospholipase D signalling pathway activation. This finding suggests that targeting these signalling pathways may be a promising novel therapeutic approach in OSCC which may improve prognosis in patients undergoing immunotherapy.
HostingRepository	iProX
AnnounceDate	2022-12-22
AnnouncementXML	Submission_2023-10-26_19:08:34.130.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lijuan Gao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-21 18:47:25	ID requested
1	2023-10-16 19:03:12	announced
⏵ 2	2023-10-26 19:08:35	announced	2023-10-27: Update publication information.

Gao L, Chen Y, A metabolomic and proteomic study to elucidate the molecular mechanisms of immunotherapy resistance in patients with oesophageal squamous cell carcinoma. Biomed Rep, 18(5):36(2023) [pubmed]

submitter keyword: oesophageal squamous cell carcinoma (OSCC), immunotherapy, PD-1 monoclonal antibody, proteomics, metabolics

Lijuan Gao
contact affiliation	Wuhan University
contact email	shirely2020@163.com
lab head
Lijuan Gao
contact affiliation	Wuhan University
contact email	shirely2020@163.com
dataset submitter

iProX dataset URI