Identification of potential prognostic biomarkers for node-negative breast tumours by proteomic analysis: A multicentric 2004 national PHRC study

Abstract

Abstract. We used a 2D-electrophoresis (2-DE) proteomic approach to identify novel biomarkers in node-negative breast cancers. This retrospective study focused on a population of patients with ductal pN0M0 tumours. A subset of patients who developed metastases and in whose tumours were found high levels of uPA and PAI-1 (metastatic relapse, MR: n=20) were compared to another subset in whom no metastatic relapse occurred and whose tumours were found to have low levels of uPA and PAI-1 (no relapse, NR: n=21). We used a 2-DE coupled with MS approach to screen cytosol fractions using two pH-gradient scales, a broad scale (3.0-11.0) and a narrower scale focussing in on a protein rich region (5.0-8.0). This study was conducted on 41 cytosol specimens analyzed in duplicate on two platforms. The differential analysis of more than 2,000 spots in 2-DE gels, obtained on the two platforms, allowed the identification of 13 proteins which were confirmed by western blotting. Two proteins, GPDA and FABP4 were down-regulated in the MR subset whereas all the others were up-regulated. An in silico analysis revealed that GMPS (GUAA), GAPDH (G3P), CFL1 (COF1) and FTL (FRIL), the most informative genes, displayed a proliferation profile (high expression in basal-like, HER2 + and luminal B molecular subtypes). Inversely, similar to FABP4, GPD1 [GPDA] displayed a high expression in luminal A subtype, a profile characteristic of tumour suppressor genes. Despite the small size of our cohort, the 2-DE analysis gave interesting results which were confirmed by the in silico analysis showing that some of the corresponding genes had a strong prognostic impact in breast cancer, mostly because of their link with proliferation: GMPS, GAPDH, FTL and GPD1. A validation phase on a larger cohort is now needed before these biomarkers could be considered for use in clinical practice.

Metabolic markers GAPDH, PKM2, ATP5B and BEC-index in advanced serous ovarian cancer

“…Descotes et al used 2D-electrophoresis and Western blotting in 41 node-negative breast cancers of which 20 had metastatic relapse and 21 had no metastatic recurrence [6]. The former group had significantly higher GAPDH expression.…”

The prognostic value of glycerol‐3‐phosphate dehydrogenase 1‐like expression in head and neck squamous cell carcinoma

“…GPD1L is one of the down‐regulated genes, and its function in tumours is not clear . Recently, Descotes et al . identified potential prognostic biomarkers for node‐negative breast tumours by proteomic analysis; their study found that GPD1, the homologous molecule of GPD1L, was differentially expressed, allowing prediction of tumour relapse.…”

“…GPD1L is one of the down-regulated genes, and its function in tumours is not clear. 3 Recently, Descotes et al 11 identified potential prognostic biomarkers for node-nega- Underlined values represent a statistically significant difference tive breast tumours by proteomic analysis; their study found that GPD1, the homologous molecule of GPD1L, was differentially expressed, allowing prediction of tumour relapse. In our study, decreased expression of GPD1L was quantitatively detected at the mRNA level in HNSCC tissues compared with adjacent normal tissues, suggesting that GPD1L may suppress initiation and development of HNSCC.…”

Clinical proteomics and breast cancer

“…25 Equally, addressing the same area with the help of MS technology demonstrated Ferritin light chain (FTL) as a potential biomarker in node negative breast cancer tissue. 26 In this multicentre study, Jezequel et al successfully validated the prognostic value of FTL where its overexpression was associated with a more aggressive phenotype in this subgroup of patients. In addition, this work demonstrated that FTL was stored in tissueassociated macrophages (TAM).…”