Comprehensive Analysis of Cuproptosis-Related Genes in Immune Infiltration and Prognosis in Melanoma

Abstract

Skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) is the most lethal skin cancer with increasing incidence. Regulated cell death plays an important role in tumorigenesis and serves as an important target for almost all treatment strategies. Cuproptosis is the most recently identified copper-dependent regulated cell death form that relies on mitochondria respiration. However, its role in tumorigenesis remains unknown. The correlation of cuproptosis-related genes with tumor prognosis is far to be understood, either. In the present study, we explored the correlation between cuproptosis-related genes with the prognosis of melanoma by accessing and analyzing a public database and found 11 out 12 genes were upregulated in melanoma tissues and three genes (LIPT1, PDHA1, and SLC31A1) have predictive value for the prognosis. The subgroup of melanoma patients with higher cuproptosis-related gene expression showed longer overall survival than those with lower gene expression. We chose LIPT1 for further exploration. LIPT1 expression was increased in melanoma biopsies and was an independent favorable prognostic indicator for melanoma patients. Moreover, LIPT1 expression was positively correlated with PD-L1 expression and negatively associated with Treg cell infiltration. The melanoma patients with higher LIPT1 expression showed longer overall survival than those with lower LIPT1 expression after receiving immunotherapy, indicating the prognostic predictive value of LIPT1. Finally, a pan-cancer analysis indicated that LIPT1 was differentially expressed in diverse cancers as compared to normal tissues and correlated with the expression of multiple immune checkpoints, especially PD-L1. It could serve as a favorable prognosis indicator in some cancer types. In conclusion, our study demonstrated the prognostic value of cuproptosis-related genes, especially LIPT1, in melanoma, and revealed the correlation between LIPT1 expression and immune infiltration in melanoma, thus providing new clues on the prognostic assessment of melanoma patients and providing a new target for the immunotherapy of melanoma.

The Prognostic Role of Cuproptosis in Head and Neck Squamous Cell Carcinoma Patients: A Comprehensive Analysis

“…We carried out the survival analyses using the values of the risk score and observed that a higher risk score was associated with a poor prognosis (p < 0:05, Figures 2(b), S1(a), and S1(b)), which was further validated using the CPTAC clinical data (Figure 2(c)). It has been reported the expression of CRGs may be correlated with disease grade in clear renal cell carcinoma, hepatocellular carcinoma, and melanoma [27][28][29]. In our study, the high-risk group was significantly related to a higher clinical T stage (Figure 2(d)), HPV -(Figure 2(e)), PD/SD (Figure 2(f)), higher pathologic T stage (Figure S1(c)), a higher number of positive lymph nodes (Figure S1(d)), and higher grade and shorter PFS (Figure S1(e)) in the TCGA cohort.…”

Construction of five cuproptosis-related lncRNA signature for predicting prognosis and immune activity in skin cutaneous melanoma

“…Besides, Shen et al identified 10 N6-methyladenosine (m6A)-related lncRNAs as significantly related to the prognosis of SKCM and further constructed a risk model by using bioinformatics analysis ( Shen et al, 2022 ). There is, however, no knowledge of the role of lncRNAs in cuproptosis of the SKCM, the latest results of Haozhen Lv et al showed that the three Cuproptosis-related genes, LIPT1, PDHA1, and SLC31A1, have a predictive effect on the prognosis of SKCM patients, which also gave us a hint for further research to a certain extent ( Lv et al, 2022 ). So, we decided to use bioinformatics analysis to uncover the relationship between cuproptosis, lncRNA, and SKCM.…”

Identification of a cuproptosis related chromatin regulators signature for lung adenocarcinoma

“…Cuproptosis, a novel cell death process distinct from any already known mechanisms, has recently been suggested and explored [5]. More research is being conducted to determine how and to what extent cuproptosis affects cancer progression [6,7]. In addition, former research has already confirmed that chromatin regulators (CRs) could be served for prognostic prediction in a variety of malignancies [8,9,10,11,12].…”