Leveraging a cuproptosis-based signature to predict the prognosis and drug sensitivity of cutaneous melanoma

Abstract

Immunotherapy is a vital treatment for patients with cutaneous melanoma (CM), but effective predictors to guide clinical immunotherapy are lacking. Cuproptosis is a newly discovered mode of cell death related to tumorigenesis. Exploring the relationship between the mode of cuproptosis and the effect of immunotherapy on CM could better guide clinical management. We clustered all patients with CM in the Cancer Genome Atlas (TCGA) database based on cuproptosis-related genes (CRGs). Prognosis, immunotherapeutic effect, tumor microenvironment score, expression of CD274, CTLA4, and PDCD1, and abundance of CD8 + T infiltration in group A were higher than in group B. Using a combination of LASSO and COX regression analysis, we identified 10 molecules significant to prognosis from differentially expressed genes between the two groups and constructed a cuproptosis-related scoring system (CRSS). Compared with the American Joint Committee on Cancer (AJCC) staging system, CRSS more accurately stratified CM patient risk and guided immunotherapy. CRSS successfully stratified risk and predicted the effect of immunotherapy in 869 patients with eight CM immunotherapy datasets and multiple other tumor immunotherapy cohorts. The nomogram model, which combined AJCC stage and CRSS, greatly improved the ability and accuracy of prognosis prediction. In general, our cuproptosis-related scoring system and nomogram model accurately stratified risk in CM patients and effectively predicted prognosis and the effect of immunotherapy in CM patients.

Construction and validation of eight cuproptosis-related lncRNAs signature for predicting prognosis and immune response in melanoma

“…The study by Rodríguez et al provided insights into the mechanism governing the function of CD + T cells and DCs in the antitumor response, and they discovered that advanced stage III and IV melanoma had considerably lower densities of cDC1s and CD8 T cells [48]. There is other study that has also observed reduced tumorin ltrating CD8 + T cell values in SKCM patients [49]. This study's results on immune in ltration analysis align with those of Yang et al, who found decreased CD8 + T-cell in ltration of the high risk group in colorectal cancer patients [50].…”

Characterization of prognosis and immune infiltration by a novel glutamine metabolism-related model in cutaneous melanoma

“…Moreover, the expression level of a single gene may be affected by multiple factors, which may lead to unreliable prognostic prediction results of a single gene as an independent prognostic factor (Huang et al, 2021). Furthermore, previous studies have demonstrated the ability of multiple genes to effectively predict outcomes in melanoma patients (Xu et al, 2022;Liu et al, 2023). Consequently, our study then screened six OS-associated genes (IL-18, SEMA6A, PAEP, TNFRSF17, AIM2, and CXCL10) to establish risk score.…”

Stigmasterol and barasertib target cuproptosis-related prognostic model for the synergistic treatment of breast cancer.

“…These studies show the potential of cuproptosis as a promising research area for understanding the disease, although it is still poorly known in BRCA. Recent attempts have been made to construct CRG signatures to predict tumor prognosis and develop novel and effective treatments [17]. Copper ion carriers and chelators have the potential to be effective therapeutic options for tumor treatment, according to several research [18].…”