PXD012616

PXD012616 is an original dataset announced via ProteomeXchange.

Title	Combined proteomics and miRNomics of a glioblastoma immunotherapy cohort reveals resistance factor candidates and novel counterstrategy concepts
Description	Glioblastoma is the most prevalent and aggressive form of brain cancer. With a median overall survival of ~20 months under current standard therapy (surgery, chemotherapy, radiotherapy), novel treatment approaches are desperately needed. Immunotherapies are being investigated in clinical trials but failed so far. This includes a recent phase II clinical trial with a personalized immunotherapy based on tumor lysate-charged dendritic cells (NCT01213407). Here, we investigated tumor tissue from patients from this trial to explore glioblastoma (immuno)resistance factors and strategies to overcome them. We followed an innovative approach of combining mass spectrometry-based quantitative proteomics (n=36) with microRNA sequencing plus RT-qPCR (n=38). Protein quantification identified e.g. huntingtin interacting protein 1 (HIP1), retinol binding protein 1 (RBPP1), ferritin heavy chain (FTH1) and focal adhesion kinase 2 (FAK2) as resistance factor candidates. MicroRNA analysis identified miR-216b, miR-216a, miR-708 and let-7i as molecules potentially associated with overcoming resistance as they were enriched in patients with a comparably longer survival. In silico pathway prediction indicated they down-regulate the focal adhesion pathway – among others. FAK2 was enriched in short-term surviving immunotherapy patients. In vitro, FAK inhibitors prevented the formation of glioblastoma cell adhesion in the form of gliomaspheres. Taken together, we here mapped possible drivers of glioblastoma’s immuno)resistance in one of the largest DC vaccination tissue analysis cohorts so far – demonstrating usefulness and feasibility of combined proteomics/miRNomics approaches. Future research should investigate agents that sensitize glioblastoma to (immuno)therapy – e.g. targeting focal adhesion. Small-molecule inhibitors or microRNAs capable of altering multiple pathways at once are candidates to explore.
HostingRepository	PRIDE
AnnounceDate	2020-01-29
AnnouncementXML	Submission_2020-01-29_06:29:24.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hannes Hahne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-07 04:01:21	ID requested
⏵ 1	2020-01-29 06:29:26	announced

Erhart F, Hackl M, Hahne H, Buchroithner J, Meng C, Klingenbrunner S, Reitermaier R, Fischhuber K, Skalicky S, Berger W, Spiegl-Kreinecker S, L, ö, tsch D, Ricken G, Kuster B, W, ö, hrer A, Widhalm G, Hainfellner J, Felzmann T, Dohnal AM, Marosi C, Visus C, Combined proteomics/miRNomics of dendritic cell immunotherapy-treated glioblastoma patients as a screening for survival-associated factors. NPJ Vaccines, 5(1):5(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: Glioblastoma, clinical cohort, immune oncology, proteomics

Hannes Hahne
contact affiliation	OmicScouts GmbH Lise-Meitner-Str. 30 D-85354 Freising Germany
contact email	hannes.hahne@omicscouts.com
lab head
Hannes Hahne
contact affiliation	OmicScouts GmbH
contact email	hannes.hahne@omicscouts.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/01/PXD012616

PRIDE project URI

• PRIDE
  1. PXD012616
     1. Label: PRIDE project
     2. Name: Combined proteomics and miRNomics of a glioblastoma immunotherapy cohort reveals resistance factor candidates and novel counterstrategy concepts