PXD022919

PXD022919 is an original dataset announced via ProteomeXchange.

Title	Quantitative proteomic analysis reveals sophisticated metabolic alteration and identifies FMNL1 as a diagnostic and prognostic marker in clear cell renal cell carcinoma
Description	Purpose: In this study, we have undertaken the whole proteomic analysis and got a better understanding of biological processes involved in the development and progression of ccRCC. We hope promising biomarkers can be uncovered to facilitate early diagnosis, predict the prognosis and progression, more importantly, to be applied as potential therapeutic targets. Experimental design: Fresh frozen tissue samples were surgically resected from patients with local or locally advanced ccRCC. Trypsin digested proteins were analyzed using TMT-based LC-MS/MS proteomic approach, followed by bioinformatic analysis. A potential prognostic marker FMNL1, annotated with actin cytoskeleton assembly and cell migration, was chosen to be validated in TCGA_KIRC datasets(n=597), further validation sets(n=20) and expanded validation sets(n=97). Results: A total of 657 differentially expressed proteins were identified and quantified between ccRCC and adjacent normal tissues (p-value<0.05, FC>2 or<1/2), of which 186 proteins were up-regulated and 471 proteins were down-regulated. Bioinformatic analysis showed enriched metabolic biological processes and pathways including oxidative phosphorylation, valine, leucine and isoleucine degeneration, propanoate metabolism, fatty-acid degeneration, TCA cycle, glycolysis/gluconeogenesis, etc. Univariate and multivariate analysis defined FMNL1 as an independent negative prognostic marker in the TCGA datasets. High expression of FMNL1 correlated significantly with tumor stage, T stage, lymph node metastasis(P<0.05), and distant metastasis(P<0.05) both in the TCGA-KIRC datasets and expanded validation sets. And KM survival curve illustrated that patients with high FMNL1 protein level had shorter OS time in the expanded validation sets (p=0.0273) Conclusion and clinical relevance: The proteomic results uncovered sophisticated metabolic reprogramming of ccRCC and indicated that the upregulation of rate-limiting enzymes in glycolysis and mitochondrial impairment may be the cause of metabolic reprogramming in ccRCC. Moreover, FMNL1 has been identified as a diagnostic and prognostic marker, and may be implicated in the progression of ccRCC.
HostingRepository	PRIDE
AnnounceDate	2022-02-16
AnnouncementXML	Submission_2022-02-16_10:11:02.423.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	桂 马
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-04 03:04:53	ID requested
⏵ 1	2022-02-16 10:11:03	announced

Ma G, Wang Z, Liu J, Fu S, Zhang L, Zheng D, Shang P, Yue Z, Quantitative proteomic analysis reveals sophisticated metabolic alteration and identifies FMNL1 as a prognostic marker in clear cell renal cell carcinoma. J Cancer, 12(21):6563-6575(2021) [pubmed]

submitter keyword: ccRCC

proteomics

energy metabolism

prognosis

FMNL1

Gui Ma
contact affiliation	Lanzhou University
contact email	1005232469@qq.com
lab head
桂 马
contact affiliation	The Second Clinical College of Lanzhou University
contact email	1005232469@qq.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022919
     1. Label: PRIDE project
     2. Name: Quantitative proteomic analysis reveals sophisticated metabolic alteration and identifies FMNL1 as a diagnostic and prognostic marker in clear cell renal cell carcinoma