PXD035408

PXD035408 is an original dataset announced via ProteomeXchange.

Title	An integrated multi-omics analysis of rectal cancer patients identified POU2F3 as a putative druggable target and 7-hub genes as predictive biomarkers of response to neoadjuvant therapy
Description	Rectal cancer (RC) accounts for one-third of colorectal cancer (CRC), and 40% of these are locally advanced rectal cancer (LARC) at diagnosis. The use of neoadjuvant chemoradiotherapy (nCRT) significantly reduces the rate of local recurrence compared to adjuvant therapy or surgery alone. However, after nCRT, up to 40-60% of patients show a poor pathological response, while only about 20% achieve a pathological complete response. In this scenario, the identification of novel predictors of tumor response to nCRT are urgently needed to reduce LARC mortality, and to spare poorly responding patients from unnecessary treatments. Therefore, by combining gene and microRNA expression datasets with proteomic data from LARC patients, we developed an integrated network centered on seven hub-genes putatively involved in the response to nCRT. In an independent validation cohort of LARC patients, we confirmed the differential expression of NFKB1, TRAF6 and STAT3 depending on a response to nCRT. In addition, the functional enrichment analysis also revealed that these genes are strongly related to hallmarks of cancer and inflammation, whose dysfunction may causatively affect LARC patient’s response to nCRT. Furthermore, by constructing the transcription factor-module network, we hypothesized a protective role of POU2F3 gene, which could be used as a new drug target in LARC patients. Finally, we identified and in vitro tested entinostat, a histone deacetylase (HDAC) inhibitor, as a chemical compound that could be combined with classical therapeutic regimen in order to design more efficient therapeutic strategies in LARC.
HostingRepository	PRIDE
AnnounceDate	2023-01-05
AnnouncementXML	Submission_2023-01-05_02:54:14.540.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	EdoardoD'Angelo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-20 00:55:31	ID requested
⏵ 1	2023-01-05 02:54:14	announced

Dataset with its publication pending

submitter keyword: POU2F3, integrative computational biology, molecular signature, entinostat,rectal cancer, neoadjuvant therapy, multi-omics analysis

MarcoAgostini
contact affiliation	University of Padova, Department of Surgery, Oncology and Gastroenterology
contact email	m.agostini@unipd.it
lab head
EdoardoD'Angelo
contact affiliation	University of Padova
contact email	edoardo.dangelo@unipd.it
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/2023/01/PXD035408

PRIDE project URI

• PRIDE
  1. PXD035408
     1. Label: PRIDE project
     2. Name: An integrated multi-omics analysis of rectal cancer patients identified POU2F3 as a putative druggable target and 7-hub genes as predictive biomarkers of response to neoadjuvant therapy