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      The value of cuproptosis-related differential genes in guiding prognosis and immune status in patients with skin cutaneous melanoma

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          Abstract

          Background: Skin cutaneous melanoma (SKCM) is one of the most common cutaneous malignancies, which incidence is increasing. Cuproptosis is a new type of programming cell death recently reported, which may affect the progression of SKCM.

          Method: The mRNA expression data of melanoma were obtained from the Gene Expression Omnibus and the Cancer Genome Atlas databases. We constructed a prognostic model according to the cuproptosis-related differential genes in SKCM. Finally, real-time quantitative PCR was performed to verify the expression of cuproptosis-related differential genes in patients with different stages of cutaneous melanoma.

          Results: We detected 767 cuproptosis-related differential genes based on 19 cuproptosis-related genes, and screened out 7 differential genes to construct a prognostic model, which including three high-risk differential genes (SNAI2, RAP1GAP, BCHE), and four low-risk differential genes (JSRP1, HAPLN3, HHEX, ERAP2). Kaplan-Meier analysis indicated that SKCM patients with low-risk differential genes signals had better prognosis. The Encyclopedia of Genomes results manifested that cuproptosis-related differential genes are not only involved in T cell receptor signaling channel, natural killer cell mediated cytotoxicity, but also chemokine signaling pathway and B cell receptor signaling pathway. In our risk scoring model, the receiver operating characteristic (ROC) values of the three-time nodes are 0.669 (1-year), 0.669 (3-year) and 0.685 (5-year), respectively. Moreover, the tumor burden mutational and immunology function, cell stemness characteristics and drug sensitivity have significant differences between low-risk group and high-risk group. The mRNA level of SNAI2, RAP1GAP and BCHE in stage Ⅲ+Ⅳ SKCM patients was significantly higher than that in stage Ⅰ+Ⅱ patients, while the level of JSRP1, HAPLN3, HHEX and ERAP2 in stage Ⅰ+Ⅱ SKCM patients was more remarkable higher than that in stage Ⅲ+Ⅳ SKCM patients.

          Conclusion: In summary, we suggest that cuproptosis can not only regulate the tumor immune microenvironment but also affect the prognosis of SKCM patients, and may offer a basic theory for SKCM patients survival studies and clinical decision-making with potentially therapeutic drugs.

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          Most cited references38

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

            This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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              Ferroptosis: an iron-dependent form of nonapoptotic cell death.

              Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon intracellular iron, but not other metals, and is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. We identify the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes. Indeed, erastin, like glutamate, inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)), creating a void in the antioxidant defenses of the cell and ultimately leading to iron-dependent, oxidative death. Thus, activation of ferroptosis results in the nonapoptotic destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                17 April 2023
                2023
                : 14
                : 1129544
                Affiliations
                Department of Plastic and Cosmetic Surgery , Xiangya Hospital , Central South University , Changsha, Hunan, China
                Author notes

                Edited by: Hongzhou Cai, Nanjing Medical University, China

                Reviewed by: Yan Han, People’s Liberation Army General Hospital, China

                Jingping Shi, Nanjing Medical University, China

                Binyu Song, Fourth Military Medical University, China

                *Correspondence: Zhexuan Li, lzxuan11733@ 123456163.com
                Article
                1129544
                10.3389/fphar.2023.1129544
                10149708
                37138850
                5dbfcdc7-19ea-4738-9356-aa229c2da0dd
                Copyright © 2023 Sun, Lei, Luo, Jiang and Li.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 December 2022
                : 03 April 2023
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                cuproptosis,prognostic model,skin cutaneous melanoma,bioinformatics,tumor mutational burden (tmb)

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