PXD021701

PXD021701 is an original dataset announced via ProteomeXchange.

Title	Large-scale and high-resolutionmass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting
Description	Esophageal cancer (EC) is anaggressive cancer type without clinically relevant molecular subtypes defined, which hinders the development of effective strategies forEC treatment. Here, we reporteda large-scale, high-resolution massspectrometry-based proteomicand phosphoproteomics profiling of EC tumor and the corresponding adjacent non-tumor tissues, revealing a catalog of proteins, phosphositesas well as pathways that are dysregulated in ECs. The EC cohort was stratified into two molecular subtypes, S1 and S2, based on proteomic analysis, withthe S2 subtype characterized by the up-regulation of spliceosome and ribosomal proteins, and being more aggressive.Moreover, we identified a subtype signature composed of ELOA and SCAF4 and constructed a subtype diagnostic model, the accuracy of which was independently validated in a large cohort of EC patients (n=295). Potential drugs were predicted for treating patients in S2 subtype, and threecandidate drugs, GW8510, Menadione and Sulconazole,were validated to significantly inhibit the proliferation and migration of EC cell lines . On the basis of nude mice with xenograft tumors, we found that treatment with the three drugs markedly reduced the size of tumors. Finally, the three drugs were shown to reverse the expression patterns of most proteins that are dysregulated in S2 subtype in KYSE150 cells.Taken together, our proteomic analysis defined subtypesand subtype signature of EC, and providedmolecular basis for finding potential treatmentsfor EC.
HostingRepository	iProX
AnnounceDate	2021-07-05
AnnouncementXML	Submission_2021-09-12_19:38:00.721.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yaohui He
SpeciesList	scientific name: Trichuris sp. ex Homo sapiens JP-2011; NCBI TaxID: 1035824;
ModificationList	phosphorylation without neutral loss
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-27 20:49:59	ID requested
1	2021-07-04 20:14:44	announced
⏵ 2	2021-09-12 19:38:01	announced	2021-09-13: Update publication information.

Liu W, Xie L, He YH, Wu ZY, Liu LX, Bai XF, Deng DX, Xu XE, Liao LD, Lin W, Heng JH, Xu X, Peng L, Huang QF, Li CY, Zhang ZD, Wang W, Zhang GR, Gao X, Wang SH, Li CQ, Xu LY, Liu W, Li EM, Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting. Nat Commun, 12(1):4961(2021) [pubmed]

submitter keyword: Esophageal cancer，TMT，Proteomics

Liyan Xu
contact affiliation	Institute of Oncologic Pathology, Shantou University Medical College
contact email	lyxu@stu.edu.cn
lab head
Yaohui He
contact affiliation	School of Pharmaceutical Sciences,Xiamen University
contact email	yaohuihe@stu.xmu.edu.cn
dataset submitter

iProX dataset URI