Dataset Information

Data-independent acquisition (DIA)-based proteomics for the identification of biomarkers in tissue washings of endometrial cancer

ABSTRACT: : Endometrial cancers (ECs), which are mainly adenocarcinomas arising from the uterine endometrium. In this work, we employed data-independent acquisition (DIA) mass spectrometry (MS)-based label-free quantification (LFQ-MS) proteomics to analyze the proteome of tissue washings collected from 25 control subjects (CTRL), 25 patients with low-grade type 1 endometrial cancer (EC), and 24 patients with high-grade type 1 EC. Following quantification and statistical analysis, we identified 42 proteins able to discriminate CTRL from EC patients, and 151 proteins differentiating high-grade EC cases from low-grade EC cases. Notably, PRRC2A and SYDE2 effectively distinguished both EC patients from controls and advanced EC cases from low-grade EC cases. Validation by Western blot analysis in an independent cohort comprising 19 CTRL, 19 patients with low-grade EC, and 19 patients with high-grade EC confirmed the upregulation of PRRC2A and SYDE2. These proteins are implicated in the translocation of SLC2A4, regulation of MECP2, and extracellular matrix (ECM) proteoglycan pathways, all of which are associated with tumor growth. Our results demonstrate that DIA-based proteomic analysis of tissue washings enables the identification of potential biomarkers for endometrial cancer (EC). Moreover, this study highlights tissue washings as a promising biological fluid for biomarker discovery in EC.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Uterine Endometrium, Endometrium

DISEASE(S): Endometrial Cancer

SUBMITTER: Michelangelo Aloisio

LAB HEAD: Blendi Ura

PROVIDER: PXD069126 | Pride | 2025-12-22

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	LAV_TISS_104_ADK_AVANZATO.raw.zip	Raw
	LAV_TISS_111_CTR.raw.zip	Raw
	LAV_TISS_112_ADK_TIPO1.raw.zip	Raw
	LAV_TISS_113_2_CTR.raw.zip	Raw
	LAV_TISS_113_CTR.raw.zip	Raw

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Data-Independent Acquisition (DIA)-Based Proteomics for the Identification of Biomarkers in Tissue Washings of Endometrial Cancer.

Monasta Lorenzo L Capaci Valeria V Kharrat Feras F Ciampechini Milena M Balasan Nour N Conti Andrea A Golino Valentina V Campiglia Pietro P Aloisio Michelangelo M Licastro Danilo D Di Lorenzo Giovanni G Romano Federico F Ricci Giuseppe G Ura Blendi B

International journal of molecular sciences 20251127 23

Endometrial cancers (ECs) are mainly adenocarcinomas arising from the uterine endometrium. In this work, we employed data-independent acquisition (DIA) mass spectrometry (MS)-based label-free quantification (LFQ-MS) proteomics to analyze the proteome of tissue washings collected from 25 control (CTRL) subjects, 25 patients with low-grade type 1 endometrial cancer (EC), and 24 patients with high-grade type 1 EC. Following quantification and statistical analysis, we identified 42 proteins able to ...[more]

PMID: 41373651

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Project description:Endometrial cancer (EC) is the most common female genital malignancy and the fourth most common cancer in women in the developing world1. EC has been traditionally classified into two main groups with different clinical, pathological and molecular features2,3. Type I or endometrioid endometrial carcinomas (EECs) account for about 75% of the cases and are typically estrogen-related and low-grade tumors with good prognosis that coexist or are preceded by endometrial hyperplasia, mainly diagnosed in perimenopausal women. In contrast, type II or non-endometrioid endometrial carcinomas (NEECs) are high-grade aggressive tumors associated with endometrial atrophy and poor prognosis, unrelated to estrogen and diagnosed in older women. These comprise several histological subtypes, being the most common the serous carcinomas (SEC)4. In recent years numerous large-scale studies of primary endometrioid and serous tumors have been performed5, revealing new mutated genes and establishing a new molecular subclassification based on the results obtained by The Cancer Genome Atlas (TCGA) consortium6, which implies different clinical outcomes. More recently, the genomic evolution of EC has been analyzed through a comparative study of samples from endometrial atypical hyperplasia, primary tumors and paired metastases7, revealing the presence of intratumor heterogeneity as previously described in primary EC and other tumor types8,9. However an in-depth study considering multiple regions from primary tumor and paired metastases has not been performed up to now to our knowledge. Here we analyze by whole-exome sequencing (WES), massive parallel targeted sequencing and array comparative genomic hybridization (aCGH) the clonal evolution and intratumor heterogeneity of 7 endometrioid and 3 serous metastatic endometrial carcinomas. Different locations from the primary tumor as well as from their paired metastases were included in the study, allowing the reconstruction of the spatial and temporal phylogenetic evolution of the tumor. Different phylogenetic evolution patterns were identified, independently of the classical histological or molecular classification of the tumor, although similar patterns were found in ovarian metastasis and recurrent disease.