4.7 Article

Inflammatory landscape in Xeroderma pigmentosum patients with cutaneous melanoma

Journal

SCIENTIFIC REPORTS
Volume 12, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41598-022-17928-z

Keywords

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Funding

  1. Tunisian Ministry of Public Health
  2. Ministry of Higher Education and Scientific Research [LR16IPT05]
  3. Slovenian Research Agency (ARRS) program [P1-0104, P1-0390]
  4. Projet Collaborative Interne (PCI_ Melanoma, IPT)

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Xeroderma pigmentosum (XP) is a DNA repair disease associated with early skin cancers like melanoma. Inflammatory genes in the melanoma microenvironment have potential as biomarkers for prognosis and identifying therapeutic targets. This study used PCR array to evaluate the expression of inflammatory genes in XP patients and sporadic melanoma, identifying potential biomarkers for tumorigenesis and patient survival. The study also observed alterations in immune response in XP patients, suggesting a potential prognostic biomarker for melanoma outcome.
Xeroderma pigmentosum (XP) is a DNA repair disease that predisposes to early skin cancers as cutaneous melanoma. Melanoma microenvironment contains inflammatory mediators, which would be interesting biomarkers for the prognosis or for the identification of novel therapeutic targets. We used a PCR array to evaluate the transcriptional pattern of 84 inflammatory genes in melanoma tumors obtained from XP patients (XP-Mel) and in sporadic melanoma (SP-Mel) compared to healthy skin. Commonly expressed inflammatory genes were further explored via GTEx and GEPIA databases. The differentially expressed inflammatory genes in XP were compared to their expression in skin exposed to UVs, and evaluated on the basis of the overall survival outcomes of patients with melanoma. Monocyte subsets of patients with SP-Mel, XP and healthy donors were also assessed. PCR array data revealed that 34 inflammatory genes were under-expressed in XP-Mel compared to SP-Mel. Differentially expressed genes that were common in XP-Mel and SP-Mel were correlated with the transcriptomic datasets from GEPIA and GTEx and highlighted the implication of KLK1 and IL8 in the tumorigenesis. We showed also that in XP-Mel tumors, there was an overexpression of KLK6 and KLK10 genes, which seems to be associated with a bad survival rate. As for the innate immunity, we observed a decrease of intermediate monocytes in patients with SP-Mel and in XP. We highlight an alteration in the immune response in XP patients. We identified candidate biomarkers involved in the tumorigenesis, and in the survival of patients with melanoma. Intermediate monocyte's in patients at risk could be a prognostic biomarker for melanoma outcome.

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