PXD069296-1

PXD069296 is an original dataset announced via ProteomeXchange.

Title	A NIR fluorotag reporter CETIF6a enables bright pan-tumor labeling and functional proteomic profiling
Description	Tumor-seeking fluorescent dyes enable precise lesion localization by recognizing overexpressed receptors, providing critical adjunctive technology for cancer histopathology. However, tumor heterogeneity and poorly understood targeting mechanisms limit their efficacy. To address this, we engineered CETIF6a, a click chemistry-compatible heptamethine cyanine dye, for multi-cancer targeting, intraoperative histopathology, and proteome-wide target identification. Using integrated proteomics, three-dimensional histological electrophoresis, structural biology, and functional validation across multi-cancer types, we demonstrated superior margin delineation (> 90% concordance with H&E) of CETIF6a in cervical squamous, breast, thyroid, and cholangio cancer via molecular weight-resolved fluorescence, eliminating non-covalent background. Identification of the dye’s targets via quantitative proteomics revealing 5–15 times more tumor-specific proteins than paracancerous tissues, with PCNA and DNAJC9 critically involved in cervical squamous carcinoma demarcation covalently bound via nucleophilic substitution at cysteine thiols within hydrophobic cavities. Pan-cancer target synergy through 491 conserved tumor-enriched proteins enriched in ribosomal, proteasomal and metabolic pathways overcoming heterogeneity. Structural convergence of targets (Foldseek clustering, 30% similarity) revealing a dominant functional cluster (63 proteins) enriched in cancer invasion pathways, with ERK1-Cys178 as a key hub stabilized by hydrophobic interactions. CETIF6a’s modifiable scaffold enables dual applications in intraoperative tumor diagnosis and targeted therapy, paving the way for system-wide probe optimization.
HostingRepository	iProX
AnnounceDate	2025-10-10
AnnouncementXML	Submission_2025-10-10_01:22:18.229.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jia Li
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-10 01:22:05	ID requested
⏵ 1	2025-10-10 01:22:18	announced

Dataset with its publication pending

submitter keyword: Tumor-seeking dyes, Click chemistry, Intraoperative rapid histopathological diagnosis, Three-dimensional histological electrophoresis, Proteome-wide analysis

Shoujun Zhu
contact affiliation	State Key Laboratory of Supramolecular Structure and Materials, Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun 130012, P.R. China.
contact email	sjzhu@jlu.edu.cn
lab head
Jia Li
contact affiliation	Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun 130021, P. R. China.
contact email	lijia0204@jlu.edu.cn
dataset submitter

iProX dataset URI