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.

Cesati, M., Scatozza, F., D'Arcangelo, D., Antonini-Cappellini, G.c., Rossi, S., Tabolacci, C., et al. (2020). Investigating serum and tissue expression identified a cytokine/chemokine signature as a highly effective melanoma marker, 12(12) [10.3390/cancers12123680].

Investigating serum and tissue expression identified a cytokine/chemokine signature as a highly effective melanoma marker

Cesati M.;
2020-12-08

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.
8-dic-2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore ING-INF/05 - SISTEMI DI ELABORAZIONE DELLE INFORMAZIONI
English
Con Impact Factor ISI
Cytokines
Machine learning
Melanoma markers
Principal component analysis
Support Vector Machine
https://www.mdpi.com/2072-6694/12/12/3680
Cesati, M., Scatozza, F., D'Arcangelo, D., Antonini-Cappellini, G.c., Rossi, S., Tabolacci, C., et al. (2020). Investigating serum and tissue expression identified a cytokine/chemokine signature as a highly effective melanoma marker, 12(12) [10.3390/cancers12123680].
Cesati, M; Scatozza, F; D'Arcangelo, D; Antonini-Cappellini, Gc; Rossi, S; Tabolacci, C; Nudo, M; Palese, E; Lembo, L; Di Lella, G; Facchiano, F; Facchiano, A
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
cancers-12-03680-v3.pdf

accesso aperto

Descrizione: Articolo principale
Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 5.83 MB
Formato Adobe PDF
5.83 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/262463
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 10
social impact