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  3. In-Depth Proteomic Analysis of Paraffin-Embedded Tissue Samples from Colorectal Cancer Patients Revealed TXNDC17 and SLC8A1 as Key Proteins Associated with the Disease

In-Depth Proteomic Analysis of Paraffin-Embedded Tissue Samples from Colorectal Cancer Patients Revealed TXNDC17 and SLC8A1 as Key Proteins Associated with the Disease

  • J Proteome Res. 2024 Nov 1;23(11):4802-4820. doi: 10.1021/acs.jproteome.3c00749.
Ana Montero-Calle 1 2,  María Garranzo-Asensio 1,  Carmen Poves 3,  Rodrigo Sanz 4,  Jana Dziakova 4,  Alberto Peláez-García 5,  Vivian de Los Ríos 6,  Javier Martinez-Useros 7 8,  María Jesús Fernández-Aceñero 9,  Rodrigo Barderas 1 2 10
Affiliations

Affiliations

  • 1 Chronic Disease Programme (UFIEC), Instituto de Salud Carlos III, Majadahonda, E-28220 Madrid, Spain.
  • 2 Proteomics Core UCCTs, Instituto de Salud Carlos III, Majadahonda, E-28220 Madrid, Spain.
  • 3 Gastroenterology Unit, Hospital Universitario Clínico San Carlos, E-28040 Madrid, Spain.
  • 4 Surgical Digestive Department, Hospital Universitario Clínico San Carlos, E-28040 Madrid, Spain.
  • 5 Molecular Pathology and Therapeutic Targets Group, Hospital La Paz Institute for Health Research (IdiPAZ), E-28046 Madrid, Spain.
  • 6 Centro de Investigaciones Biológicas, CSIC, E-28040 Madrid, Spain.
  • 7 Translational Oncology Division, OncoHealth Institute, Health Research Institute-Fundación Jiménez Díaz, Fundación Jiménez Díaz University Hospital/Universidad Autónoma de Madrid (IIS-FJD/UAM), E-28040 Madrid, Spain.
  • 8 Area of Physiology, Department of Basic Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University, Alcorcón, E-28922 Madrid, Spain.
  • 9 Surgical Pathology Department, Hospital Clínico San Carlos, E-28040 Madrid, Spain.
  • 10 CIBER of Frailty and Healthy Aging (CIBERFES), E-28029 Madrid, Spain.
PMID: 39441737 DOI: 10.1021/acs.jproteome.3c00749
Abstract

A deeper understanding of colorectal Cancer (CRC) biology would help to identify specific early diagnostic markers. Here, we conducted quantitative proteomics on FFPE healthy, adenoma, and adenocarcinoma tissue samples from six stage I sporadic CRC patients to identify dysregulated proteins during early CRC development. Two independent quantitative 10-plex TMT experiments were separately performed. After protein extraction, trypsin digestion, and labeling, proteins were identified and quantified by using a Q Exactive mass spectrometer. A total of 2681 proteins were identified and quantified after data analysis and bioinformatics with MaxQuant and the R program. Among them, 284 and 280 proteins showed significant upregulation and downregulation (expression ratio ≥1.5 or ≤0.67, p-value ≤0.05), respectively, in adenoma and/or adenocarcinoma compared to healthy tissue. Ten dysregulated proteins were selected to study their role in CRC by WB, IHC, TMA, and ELISA using tissue and plasma samples from CRC patients, individuals with premalignant colorectal lesions (adenomas), and healthy individuals. In vitro loss-of-function cell-based assays and in vivo experiments using three CRC cell lines with different metastatic properties assessed the important roles of SLC8A1 and TXNDC17 in CRC and liver metastasis. Additionally, SLC8A1 and TXNDC17 protein levels in plasma possessed the diagnostic ability of early CRC stages.

Keywords

FFPE tissue; SLC8A1; TMT; TXNDC17; colorectal cancer; quantitative proteomics.

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