Dados do Resumo

Título

Autophagy-related gene expression in cutaneous melanoma: insights into prognosis and therapeutic targets

Introdução

Cutaneous Melanoma (CM), ranked as the 19th most common cancer globally, has experienced a decline in mortality rates from 2013 to 2017, primarily attributed to advancements in precision medicine. Our research emphasizes the significance of autophagy, a cellular process implicated in cancer growth and resistance, in the prognosis and treatment of MC.

Objetivo

To contribute in the oncology field, we propose to identify critical autophagy-related genes that could be predictive biomarkers for disease recurrence or tumor progression.

Métodos

We used the Gene Expression Omnibus GPL1930 public database and Gene Expression Omnibus GSE17275 to analyze the expression profile of autophagy-related genes in 60 MC patients with primary (20/60 PCM) or metastatic (40/60 MCM) diseases. From the 4,494 genes evaluated, 253 were associated with autophagy or regulated by the transcription factor EB (TFEB), the principal factor in the CLEAR (Coordinated Lysosomal Expression and Regulation) gene network.

Resultados

Nine genes - CAMKK2, CDKN1B, HRAS, MCM2, MDM2, OPTN, PLCE1, PPP2R2C, and S100A9 - exhibited significant differential expression. In PCM patients, CAMKK2, MCM2, OPTN, PPP2R2C, and S100A9 were notably expressed. Conversely, CDKN1B, HRAS, and MDM2, believed to activate autophagy, were more significantly expressed in MCM patients. Significant associations were discovered between patient staging and the genes BECN1, IFNGR1, KEAP1, NDRG1, OPTN, PIK3CB, PLD2, PPP2R1B, PPP2R2C, SIRT2, and SMPD1. Based on the Breslow T index, a critical determinant of CM's diagnosis and prognosis, DLC1, EGFR, EP300, LEPR, and SYNPO2 genes were significantly associated. Notably, EGFR was significantly related to the Breslow index (p=0.031), and the autophagy initiator BECN1, whose expression is regulated by TFEB, was associated with tumor invasiveness (p=0.059). LGALS8, involved in the selective autophagy of damaged lysosomes, showed increased expression in MCM (1.6 fold-change, p<0.04). Similarly, OPTN, another protein involved in selective autophagy, was more expressed in PCM (1.8 fold-change, p<0.021) and significantly associated with CM's clinical staging (p=0.0026).

Conclusões

Our research underscores the potential of autophagy-related genes as predictive biomarkers for CM. This study paves the way for further investigations into the role of autophagy in cancer prognosis and treatment.

Palavras Chave

Autophagy-related genes; Primary and Metastatic disease