Abstract

Endometrial cancer (EC) is the most frequent gynaecologic cancer in postmenopausal women. We used 2D-DIGE and mass spectrometry to identify candidate biomarkers in endometrial cancer, analysing the serum protein contents of 10 patients versus 10 control subjects. Using gel-based proteomics, we identified 24 candidate biomarkers, considering only spots with a fold change in volume percentage ≥ 1.5 or intensity change ≤ 0.6, which were significantly different between cases and controls (p < 0.05). We used Western blotting analysis both in the serum and tissue of 43 patients for data validation. Among the identified proteins, we selected Suprabasin (SBSN), an oncogene previously associated with poor prognosis in different cancers. SBSN principal isoforms were subjected to Western blotting analysis in serum and surgery-excised tissue: both isoforms were downregulated in the tissue. However, in serum, isoform 1 was upregulated, while isoform 2 was downregulated. Data-mining on the TCGA and GTEx projects, using the GEPIA2.0 interface, indicated a diminished SBSN expression in the Uterine Corpus Endometrial Cancer (UCEC) database compared to normal tissue, confirming proteomic results. These results suggest that SBSN, specifically isoform 2, in tissue or serum, could be a potential novel biomarker in endometrial cancer.

Highlights

  • Endometrial cancer (EC), with an increasing incidence, is the most frequent gynaecologic cancer in postmenopausal women [1]

  • We used 2D-DIGE coupled with mass spectrometry (MS) for the proteomic study to compare the enriched serum proteomic profile of 10 controls (Cys 3) and 10 EC (Cys 5)

  • Spots of interest were subjected to in-gel digestion and LC-MS/MS analysis, and proteins were identified by searching the MS/MS data against the human section of the UniProt database

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Summary

Introduction

Endometrial cancer (EC), with an increasing incidence, is the most frequent gynaecologic cancer in postmenopausal women [1]. Most EC cases are in the early stages of the disease [2]. Uterine EC is of two types: type 1 is correlated to oestrogen and comprises 80% of cases, while type 2 is described as an independent oestrogen tumour [3]. Many factors increase the risk of developing EC, such as obesity, age, and type 2 diabetes [4]. No diagnostic test is available for EC screening. Abnormal vaginal bleeding is the most common symptom [5]. Further invasive investigations, such as hysteroscopy [6], are needed to obtain a definitive diagnosis

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