Abstract
Simple SummaryThe present study selected four genes strongly related to autoimmunity. Their expression was found to be significantly altered in melanoma patients according to a multi-validation procedure carried out on 1948 patients. Such genes may represent suitable molecular targets to further investigate the role autoimmunity may play in melanoma setup and development. Our data suggest that autoimmunity may play a beneficial role in melanoma set up, at least to some extent.(1) Background. Immune response dysregulation plays a key role in melanoma, as suggested by the substantial prognosis improvement observed under immune-modulation therapy. Similarly, the role of autoimmunity is under large investigation in melanoma and other cancers. (2) Methods. Expression of 98 autoimmunity-related genes was investigated in 1948 individuals (1024 melanoma and 924 healthy controls). Data were derived from four independent databases, namely, GEO in the selection phase, and Ist Online, GEPIA2 and GENT2, in three sequential validation-steps. ROC analyses were performed to measure the ability to discriminate melanoma from controls. Principal Component Analysis (PCA) was used to combine expression data; survival analysis was carried out on the GEPIA2 platform. (3) Results. Expression levels of NOD2, BAX, IL-18 and ADRB2 were found to be significantly different in melanoma vs. controls and discriminate melanoma from controls in an extremely effective way, either as single molecules (AUC > 0.93 in all cases) or as a profile, according to the PCA analysis. Patients showing high-expression of NOD2 and of IL-18 also show a significant survival improvement as compared to low-expression patients. (4) Conclusions. Four genes strongly related to autoimmunity show a significant altered expression in melanoma samples, highlighting the role they may play in melanoma.
Highlights
Autoimmunity is activated when the immune system recognizes target cells as nonself
Expression levels of NOD2, BAX, IL-18 and ADRB2 were found to be significantly different in melanoma vs. controls and discriminate melanoma from controls in an extremely effective way, either as single molecules (AUC > 0.93 in all cases) or as a profile, according to the Principal Component Analysis (PCA) analysis
Four genes were identified and validated in all databases, showing a significantly altered expression in melanoma vs. controls, namely NOD2, BAX, IL-18 and ADRB2, NOD2 and IL-18 appear to be interesting from a prognostic point of view since their expression was found to be related to a significant survival improvement (Figure 7)
Summary
Autoimmunity is activated when the immune system recognizes target cells as nonself. Under normal conditions and activity, the immune system reacts towards foreign molecules that are potentially harmful; for example, against molecules associated with viruses, bacteria and parasites. Under such conditions, structures recognized as self undergo immune tolerance [1]. An autoimmune pathogenesis is not demonstrated in melanoma, a relation between the immune response to melanoma and the Cancers 2022, 14, 991 disorders has been investigated for several years [5]. An autoimm pathogenesis is not demonstrated in melanoma, a relation between the2imof m19une resp to melanoma and the presence of autoimmune reactions is reported in different stu [6–9]. T9o24thhiseaalitmhythceoenxtrporless)s, idoneroivfed from 98 genes wasinindveepsetingdaetendt dinat1a9s4et8s,inndaimviedlyuaGlsD(S11032745mdealtaanseotmfraompaGtieEnOtsdaantdab9a2s4e,hIeSaTltOhynline, GE controls), deraivneddGfEroNmT2fo. ur independent datasets, namely GDS1375 dataset from GEO database, IST Online, GEPIA2 and GENT2
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