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Plasma proteomic profiling discovers molecular features associated with upper urinary tract urothelial carcinoma

ABSTRACT: Upper tract urothelial carcinoma (UTUC) is often diagnosed late and exhibits poor prognosis. Only limited data are available concerning potential noninvasive biomarkers for disease monitoring. Here, we investigated the proteomic profile of plasma in 362 UTUC patients and 239 healthy control samples. The results show 520 elevated proteins in UTUC patients are mainly involved in acute-phase response and tRNA aminoacylation pathways; while 317 descend proteins are enriched in sulfur metabolism and deubiquitination. We presented an integrated tissue-plasma proteomic approach to infer the highly specific tumor biomarkers for identify patients with muscle-invasive UTUC. We provided a protein panel that reflected lymph node metastasis, which is of interest to identify high risk and poor prognosis UTUC patients. We also identified a ten-gene signature and establishment of a prognostic nomogram predicting progression-free survival of UTUC. Finally, we further validated the biomarkers by parallel reaction monitoring (PRM) assay in a new independent cohort.

ORGANISM(S): Homo Sapiens

SUBMITTER: Chen Ding

PROVIDER: PXD043774 | iProX | Wed Jul 12 00:00:00 BST 2023

REPOSITORIES: iProX

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Plasma proteomic profiling discovers molecular features associated with upper tract urothelial carcinoma.

Qu Yuanyuan Y Yao Zhenmei Z Xu Ning N Shi Guohai G Su Jiaqi J Ye Shiqi S Chang Kun K Li Kai K Wang Yunzhi Y Tan Subei S Pei Xiaoru X Chen Yijiao Y Qin Zhaoyu Z Feng Jinwen J Lv Jiacheng J Zhu Jiajun J Ma Fahan F Tang Shaoshuai S Xu Wenhao W Tian Xi X Anwaier Aihetaimujiang A Tian Sha S Xu Wenbo W Wu Xinqiang X Zhu Shuxuan S Zhu Yu Y Cao Dalong D Sun Menghong M Gan Hualei H Zhao Jianyuan J Zhang Hailiang H Ye Dingwei D Ding Chen C

Cell reports. Medicine 20230825 9

Upper tract urothelial carcinoma (UTUC) is often diagnosed late and exhibits poor prognosis. Limited data are available on potential non-invasive biomarkers for disease monitoring. Here, we investigate the proteomic profile of plasma in 362 UTUC patients and 239 healthy controls. We present an integrated tissue-plasma proteomic approach to infer the signature proteins for identifying patients with muscle-invasive UTUC. We discover a protein panel that reflects lymph node metastasis, which is of ...[more]

PMID: 37633276

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Project description:Purpose: Due to the rarity of Merkel Cell Carcinoma (MCC), prospective clinical trials have not been practical. This study seeks to identify biomarkers to differentiate between patients with a good and poor prognosis. Methods: Patients were stratified into good, moderate or poor prognosis. Merkel cell carcinoma (MCC) patients were stratified into one of three groups based upon status 24 months following treatment. Poor prognosis patients either presented with or progressed to distant metastasis. Patients with favorable prognosis had local disease presentation with no subsequent recurrence or nodal disease at presentation with no progression during follow-up of longer than 24 months. Moderate prognosis had recurrent local disease, development of nodal metastasis, or nodal disease at presentation with no progression during follow-up of fewer than 24 months. Using ArcturusXT Laser Capture Microdissection (Molecular Devices), tumor cells were isolated from the specific areas of interest. The captured tumor tissue was subjected to RNA extraction using the Invitrogen PureLinkM-bM-^DM-" FFPE RNA Isolation Kit. The extracted RNA was analyzed for integrity with the Agilent Bioanalyzer then amplified and hybridized to Affymetrix GeneChip Human Exon 1.0 ST arrays using the NuGEN WT- OvationM-bM-^DM-" FFPE System. Results: A total of 191 genes showed significant differential expression (pM-bM-^IM-$0.05 and 1.5-fold cutoff) between the different between the good and poor prognosis groups. Keratin 20 (KRT20) and Neurofilament protein (NEFM) have been identified in previous studies as proteins of interest in MCC. Our study showed these genes to be significantly upregulated in patients with a poor prognosis. Of interest, phospholipase A2, group X was upregulated in poor responders. Phospholipases liberate arachidonic acid from cellular membranes which can be metabolized to eicosanoids through three major pathways: the cyclooxygenase (COX), the lipoxygenase (LOX) and the cytochrome P450 monooxygenase pathways. This pathway has been implicated in several cancers. Conclusions: The study identified genes with a previous association with MCC as well as some novel genes. These genes provide the basis for further research into possible biomarkers that will enable the differentiation between patients with a good and poor prognosis. Using laser capture microdissection, tumor cells of patients with a good (n=5), moderate (n=3), and poor prognosis (n=7) were isolated from paraffin embedded archival tissue of 15 patients with Merkel cell carcinoma. Affymetrix Human Exon 1.0ST microarrays were utilized to compare gene expression signatures from good and poor prognosis patients.

Dataset Information

Plasma proteomic profiling discovers molecular features associated with upper urinary tract urothelial carcinoma

Publications

Plasma proteomic profiling discovers molecular features associated with upper tract urothelial carcinoma.

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