PXD006901

PXD006901 is an original dataset announced via ProteomeXchange.

Title	Vulvar squamous cell carcinoma aggressiveness associated with differential expression of collagen and STAT1
Description	Background: Vulvar squamous cell carcinoma (vSCC) is a rare but debilitating disease. One vSCC subtype comprises tumor cells that grow and expand as a cohesive sheet of cells that “pushes” and compresses the associated lymphoplasmacytic (LPC) stroma. Another vSCC subtype features tumor cells that grow in loose association with other tumor cells and infiltrate the associated fibromyxoid (FMX) stroma consisting mainly of extracellular matrix. Clinically, infiltrative vSCC with FMX stroma (Inf/FMX) is significantly associated with lymph node metastases and recurrence. Methods: An unbiased proteomic approach was used to identify pathways that could produce these different vSCC subtypes. Formalin-fixed and paraffin-embedded tissues from 10 cases of pushing vSCC with LPC stroma (Push/LPC) and 8 cases of Inf/FMX were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Analysis identified 2,265 different proteins in the 18 samples of vSCC. Of these, 344 proteins were differentially expressed (p<0.05) by at least 4-fold between vSCC subtypes. Of these, 59 were higher and 285 lower in Inf/FMX compared to Push/LPC tumors. Consistent with the desmoplastic morphology and increased picrosirius red staining, expression of subunits of several collagens (Col 1, 3, 6, 14, 18) was higher in the more aggressive Inf/FMX tumors. In contrast, signal transducer and activator of transcription 1 (STAT1), an important regulator of several inflammatory pathways, was expressed at lower levels in the Inf/FMX tumors. This finding was confirmed by immunohistochemistry using an antibody to STAT1. An informatics analysis of the differing profiles identified differences in the integrin signaling pathway and inflammation mediated by chemokine and cytokine signaling pathway. This analysis also linked decreased expression of proteins involved antigen processing and presentation and increased expression of those with cell-matrix adhesion as processes with the more aggressive Inf/FMX vSCC subtype. Conclusions: Comparing the proteomic profiles of vSCC morphologic subtypes indicates that increased expression of collagen subunits and decreased expression of STAT1 are associated with a more aggressive tumor subtype. Informatic analyses further identify alterations in cell interaction with matrix and immune function differ with tumor aggressiveness. Identification of these pathways provides a molecular basis for understanding aggressiveness of vSCC.
HostingRepository	PRIDE
AnnounceDate	2017-12-12
AnnouncementXML	Submission_2017-12-12_07:19:36.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD006901
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Stephanie Byrum
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-07-07 07:39:30	ID requested
⏵ 1	2017-12-12 07:19:37	announced

Holthoff ER, Byrum SD, Mackintosh SG, Kelly T, Tackett AJ, Quick CM, Post SR, Vulvar squamous cell carcinoma aggressiveness is associated with differential expression of collagen and STAT1. Clin Proteomics, 14():40(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: Human, FFPE Tissue, cytokine, cell adhesion, stroma immune

Steven R. Post
contact affiliation	Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
contact email	spost@uams.edu
lab head
Stephanie Byrum
contact affiliation	UAMS
contact email	sbyrum@uams.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006901
     1. Label: PRIDE project
     2. Name: Vulvar squamous cell carcinoma aggressiveness associated with differential expression of collagen and STAT1