Dados do Trabalho

Título

Exploring Gene Candidates Linked to Prognostic Histopathological Markers in Melanoma Patients

Introdução

Melanoma is a clinical condition with significant morbidity and mortality, accounting for about 90% of skin cancer-related deaths. Faced with a rapidly progressing disease, numerous studies have been conducted aiming to identify potential prognostic biomarkers that enable the early detection of cases with a higher risk of unfavorable progression, with immunometabolism being a potential target of study.

Objetivo

Identifying genes involved in immunometabolic processes associated with histopathological prognostic markers in melanoma patients.

Métodos

Fifty-two melanoma patients were selected, with samples of primary tissue embedded in paraffin containing a minimum representation of 60% tumor cells. The material underwent hematoxylin and eosin staining for the analysis of Breslow thickness (BT), mitotic index (MI), and ulceration. RNA extraction was carried out using the RNeasy Mini Kit (Qiagen). The material was subjected to nCounter NanoString technology using the Metabolic Pathways Panel (NanoString Technologies). The results were captured in nSolverAnalysis Software v. 3.0 (NanoString Technologies), with compensation of the counts of target genes (TG) by housekeeping genes. Statistical analyses were performed using T-Student tests and Pearson's correlation in SPSS Software v.23.0, with a p-value < 0.05 considered significant. The study was approved by the Research Ethics Committee (1772/2019).

Resultados

In the case series, an average Breslow thickness (BT) of 8.5 mm (±8.1), a mitotic index (MI) of 8.5 mitoses/mm³ (±7.9), and the presence of ulceration in 63.0% of cases were identified. Out of the 748 genes evaluated, 161 genes were associated with BT, 27 with ulceration, and 64 with MI. Among these, 3 genes were highlighted for their association with all three parameters. A lower gene count (GC) of CCL19 was observed in cases with higher BT (r=-0.430; p=0.002) and MI (r=-0.324; p=0.026), with a lower count in cases with ulceration (123.8 ± 108.6 vs 237.9 ± 190.8, p=0.028). A lower GC of INMT was also identified in the presence of higher BT (r=-0.368; p=0.009) and MI (r=-0.367; p=0.011), with a lower count in patients with ulcerated lesions (27.9 ± 18.2 vs 39.7 ± 20.4, p=0.037). Furthermore, a higher GC of NDUFB11 was identified in cases with higher BT (r=0.400; p=0.004) and MI (r=0.308; p=0.035), with a higher count in the presence of ulceration (222.7 ± 63.6 vs 195.3 ± 29.9, p=0.039).

Conclusões

The genes CCL19, INMT, and NDUFB11 emerge as potential targets in the prognostic assessment of patients with advanced melanoma, highlighting the importance of evaluating immune, epigenetic, and metabolic pathways, respectively, for the characterization of the tumor microenvironment and melanoma genesis.

Palavras-chave

Immune System; Metabolism; Tumor Biomarkers.

Financiador do resumo

Fundação de Amparo à Pesquisa do Estado de São Paulo (# 19/07111-9) e Programa de Auxílio e Incentivo aos Pesquisadores do Hospital do Câncer de Barretos.