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Deciphering the Genetic Landscape of Perineural and Lymphovascular Invasion in Advanced Melanoma: Unearthing Prognostic Insights


Melanoma stands out as the subtype characterized by the highest potential for invasion and metastasis, leading to an exceptionally adverse clinical course. Prognosticating the disease, the recognition of perineural and lymphovascular invasions has demonstrated its predictive value. Thus, delving into the realm of cell signaling pathways assumes paramount significance in unraveling the intricate mechanisms that underlie cellular invasion. Moreover, this pursuit holds the potential to unearth novel prognostic biomarkers, thereby enriching our understanding of the ailment's trajectory.


This study aims to assess the correlation between genes implicated in immunometabolism and the occurrence of perineural and lymphovascular invasions among patients afflicted with advanced melanoma.


We conducted a comprehensive examination involving 52 patients diagnosed with advanced melanoma, specifically encompassing clinical stages III and IV. These patients were selected based on the availability of primary tumor samples preserved in paraffin blocks, with an emphasis on samples representing no less than 60% of tumor cells. The assessment encompassed a multifaceted approach. Initial histopathological scrutiny aimed to identify instances of lymphovascular invasion (IL) and perineural invasion (IP). Subsequently, RNA extraction was meticulously executed using the RNeasy Mini Kit from Qiagen. Employing cutting-edge NanoString technology, the Metabolic Pathways Panel by NanoString Technologies was employed for gene analysis. The quantitative gene count (GC) was then acquired using the nSolver Analysis Software version 3.0, a product of NanoString Technologies. In order to derive meaningful insights, rigorous statistical analyses were undertaken. Specifically, the T-Student test was applied utilizing the SPSS Software version 23.0. Notably, a significance threshold of p-value < 0.05 was adhered to, indicating statistically significant outcomes.


Perineural invasion (PI) was observed in 9.3% of cases, while lymphovascular invasion (LI) was detected in 22.2% of instances. Exploring the genetic underpinnings, a total of 35 genes exhibited associations with PI, and an additional 10 genes demonstrated correlations with LI. Intriguingly, a comparative analysis uncovered two genes that were linked to both of these parameters. In particular, the gene ARID1B exhibited elevated gene counts (GC) in the presence of LI (202.7 ± 51.8 vs 164.9 ± 51.5; p=0.030) as well as PI (248.7 ± 73.0 vs 165.6 ± 45.5; p=0.001). Similarly, the ACACA gene displayed augmented GC among patients with LI (35.3 ± 13.6 vs 28.0 ± 9.5; p=0.040) and PI (42.5 ± 13.6 vs 28.3 ± 9.8; p=0.005).


The ARID1B gene is intricately linked to epigenetic mechanisms, while the ACACA gene is associated with fatty acid metabolism. The intriguing convergence of these two genes with tissue invasion parameters introduces the intriguing prospect of unexplored signaling pathways that play a role in the mechanisms underlying melanoma invasion. This phenomenon hints at their promising potential as novel biomarkers within the realm of this cancer.


Immune system; Metabolism; Tumor biomarkers.

Financiador do resumo

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


Estudo Clínico - Tumores Cutâneos


LIDIA MARIA REBOLHO BATISTA ARANTES, Vinícius Gonçalves de Souza, Bruna Pereira Sorroche, Renan de Jesus Teixeira, Katiane Tostes, Gabriela Sarti Kinker, Ana Carolina Laus, Caio Augusto Dantas Pereira, Tiago da Silva Medina, Vinícius de Lima Vazquez