Prognostic evaluation of epidermal fatty acid‐binding protein and calcyphosine, two proteins implicated in endometrial cancer using a proteomic approach

Abstract

With the aim to translate the discovery from proteomic research into clinical applications, we identified epidermal fatty acid-binding protein (E-FABP) and calcyphosine (CAPS) by MALDI-Q-TOF MS and validated their overexpressions by immunoblotting. Their expression statuses were examined by immunohistochemistry in 39 normal endometrium, 29 endometrial intraepithelial neoplasia (EIN) and 84 endometrial cancer (EC) cases. We evaluated the correlations to the clinicopathologic characteristics and determined whether these proteins had prognostic significance. Expressions of E-FABP and CAPS were increased 2.64- and 2.18-fold in EC by immunoblotting. Immunoreactivity of both E-FABP and CAPS were stronger in EC than in EIN or normal tissues (p < 0.001 and < 0.001). Stronger immunoreactivity of E-FABP and CAPS were shown to present with poor differentiation (p = 0.032 and 0.001), but no relevance was observed with staging (p = 1.368 and 4.306). Survival analysis indicated that immunoreactivity of CAPS was correlated to poor survival (p = 0.018), but E-FABP status appeared to be no correlation to the clinical outcome of patients (p = 0.865). Multivariate analysis indicated that CAPS might be an independent prognostic factor for survival in patients with EC (p = 0.008). Results demonstrated the ubiquitous overexpressions of E-FABP and CAPS in EC and the correlations to the clinicopathologic parameters. CAPS might be a potential prognostic factor for survival in patients with EC. The research pattern from proteomics to clinical specimens would have widespread applications.

Overexpression of calcyphosine is associated with poor prognosis in esophageal squamous cell carcinoma

“…Survival analysis has indicated that CAPS is a potential survival predictor in breast cancer patients receiving adjuvant tamoxifen (25). Previous studies also revealed that CAPS was an independent prognostic factor for endometrial cancer patients (15,24) and colorectal cancer patients (17 (Fig. 3).…”

“…In recent years, substantial attention has been been paid to the identification of biomarker targets, such as p53 (22) and heat shock protein 70 (23). A previous study showed that CAPS overexpression was significantly associated with histological grade in endometrial cancer (24). Another study demonstrated that CAPS could be a novel diagnostic biomarker for patients with colorectal cancer.…”

Biological markers with potential clinical value in endometrial cancer — review of the literature

“…The recent introduction of sequencing technology have aided in the discovery of new RNA molecules while providing more detailed understanding of biological pathways related to endometrial tumorigenesis [10]. Compared with traditional microarrays, which can only detect a limited number of miRNA, NGS enables in-depth characterization of the global range of miRNAs [10,11]. Also, it is suggested that genomic analysis of cells collected during Pap smears holds promise for early detection of EC [4,10].…”

“…In several papers, proteomics has been used to assess the clinical utility of biomarkers to evaluate their diagnostic and prognostic sensitivity and specificity by comparing protein profiles between pathological and normal tissue. It is belived that proteins are directly linked to the phenotype and the malignant nature of cancer, which explain the increased interest for studying global protein expression [11]. A study performed by Li et al exemplifies the value of proteomics where three potential EC-associated proteins were identified; Cyclophilin A (CypA), epidermal fatty acid-binding protein (E-FABP), and caclyphosine (CAPS) [11].…”

“…It is belived that proteins are directly linked to the phenotype and the malignant nature of cancer, which explain the increased interest for studying global protein expression [11]. A study performed by Li et al exemplifies the value of proteomics where three potential EC-associated proteins were identified; Cyclophilin A (CypA), epidermal fatty acid-binding protein (E-FABP), and caclyphosine (CAPS) [11]. Additionally, increase in both E-FABP and CAPS in relation to EC were also reported in a different paper [12].…”