Investigating Serum and Tissue Expression Identified a Cytokine/Chemokine Signature as a Highly Effective Melanoma Marker

Abstract

The identification of reliable and quantitative melanoma biomarkers may help an early diagnosis and may directly affect melanoma mortality and morbidity. The aim of the present study was to identify effective biomarkers by investigating the expression of 27 cytokines/chemokines in melanoma compared to healthy controls, both in serum and in tissue samples. Serum samples were from 232 patients recruited at the IDI-IRCCS hospital. Expression was quantified by xMAP technology, on 27 cytokines/chemokines, compared to the control sera. RNA expression data of the same 27 molecules were obtained from 511 melanoma- and healthy-tissue samples, from the GENT2 database. Statistical analysis involved a 3-step approach: analysis of the single-molecules by Mann–Whitney analysis; analysis of paired-molecules by Pearson correlation; and profile analysis by the machine learning algorithm Support Vector Machine (SVM). Single-molecule analysis of serum expression identified IL-1b, IL-6, IP-10, PDGF-BB, and RANTES differently expressed in melanoma (p < 0.05). Expression of IL-8, GM-CSF, MCP-1, and TNF-α was found to be significantly correlated with Breslow thickness. Eotaxin and MCP-1 were found differentially expressed in male vs. female patients. Tissue expression analysis identified very effective marker/predictor genes, namely, IL-1Ra, IL-7, MIP-1a, and MIP-1b, with individual AUC values of 0.88, 0.86, 0.93, 0.87, respectively. SVM analysis of the tissue expression data identified the combination of these four molecules as the most effective signature to discriminate melanoma patients (AUC = 0.98). Validation, using the GEPIA2 database on an additional 1019 independent samples, fully confirmed these observations. The present study demonstrates, for the first time, that the IL-1Ra, IL-7, MIP-1a, and MIP-1b gene signature discriminates melanoma from control tissues with extremely high efficacy. We therefore propose this 4-molecule combination as an effective melanoma marker.

XIAP promotes melanoma growth by inducing tumour neutrophil infiltration

“…CXCL family members such as CXCL1 and IL8 have been frequently described in human melanoma progression and their expression has been tightly associated with tumour growth and Breslow thickness (Cesati et al , 2020 ). In line, knock‐down of XIAP using specific siRNAs (Seeger et al , 2010a , 2010b ) or XIAP knock‐out by CRISPR/Cas9 technology in human melanoma cells consistently reduced IL8 secretion in all tested human tumour cells under steady‐state conditions (Figs 1 E and F and EV1E ).…”

Expression of Autoimmunity-Related Genes in Melanoma

“…We have previously used Principal Component Analysis (PCA) to identify the best genes-combination able to discriminate melanoma from controls within a large selection of nicotinamide receptors [ 20 ] and cytokines/chemokines [ 21 ]. The combined expression level of the four validated genes ( NOD2 , BAX , IL-18 and ADRB2 ) was then analyzed according to the PCA dimensionality reduction tool in the GEPIA2 database.…”

Targeting Melanoma-Initiating Cells by Caffeine: In Silico and In Vitro Approaches

“…GraphPad PRISM 5 software (GraphPad Prism Software Inc., San Diego, CA) was sued. Generation of ROC curves from expression data reported in the GDS1375 dataset and calculation of AUC data were performed as previously described [64,69].…”