The prognostic implications of cuproptosis-related gene signature and the potential of PPIC as a promising biomarker in cutaneous melanoma

IF 3.9 3区 医学 Q2 CELL BIOLOGY Pigment Cell & Melanoma Research Pub Date : 2024-08-08 DOI:10.1111/pcmr.13185
Bin Zhou, Shanshan Sha, Qi Wang, Shuomin Sun, Juan Tao, Jinjin Zhu, Liyun Dong
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Abstract

Cutaneous melanoma is the most lethal of all skin tumors. Recently, cuproptosis, a novel form of cell death linked to oxidative phosphorylation, has emerged as an important factor. However, the precise role of cuproptosis in melanoma remains unclear. Our research explored the potential links between cuproptosis-related genes, prognosis, immune microenvironments, and melanoma treatments. Significantly, cuproptosis regulators showed remarkable differences between melanoma and normal tissues, establishing their relevance to melanoma. The newly developed cuproptosis-related gene signature (CGS) demonstrated a robust ability to predict overall survival (OS) in melanoma. We constructed a novel nomogram that combined clinical features with CGS to improve predictive accuracy. In addition, the study revealed correlations between CGS and immune cell populations, including CD8+T cells, Tfh cells, B cells, and myeloid-derived suppressor cells. Within the CGS, Peptidylprolyl isomerase C (PPIC) emerged as the most strongly associated with poor prognosis and drug resistance in melanoma. PPIC was identified as a promoter of melanoma progression, enhancing cell invasiveness while concurrently suppressing CD8+T cell activation. This comprehensive study not only elucidated the intricate connections between CGS, melanoma prognosis, immune microenvironment, and drug resistance but also provided compelling evidence supporting PPIC as a promising biomarker for predicting OS in melanoma treatment.

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杯突相关基因特征对预后的影响以及 PPIC 作为皮肤黑色素瘤生物标志物的潜力。
皮肤黑色素瘤是最致命的皮肤肿瘤。最近,一种与氧化磷酸化有关的新型细胞死亡形式--杯突症成为一个重要因素。然而,杯突效应在黑色素瘤中的确切作用仍不清楚。我们的研究探索了杯突症相关基因、预后、免疫微环境和黑色素瘤治疗之间的潜在联系。值得注意的是,杯突调节因子在黑色素瘤和正常组织之间表现出显著差异,从而确定了它们与黑色素瘤的相关性。新开发的杯突相关基因特征(CGS)显示出预测黑色素瘤总生存期(OS)的强大能力。我们构建了一个新的提名图,将临床特征与 CGS 结合起来,以提高预测的准确性。此外,研究还揭示了CGS与免疫细胞群(包括CD8+T细胞、Tfh细胞、B细胞和髓源性抑制细胞)之间的相关性。在CGS中,肽基脯氨酰异构酶C(PPIC)与黑色素瘤的不良预后和耐药性关系最为密切。PPIC 被确定为黑色素瘤进展的促进因子,在增强细胞侵袭性的同时抑制 CD8+T 细胞的活化。这项全面的研究不仅阐明了CGS、黑色素瘤预后、免疫微环境和耐药性之间错综复杂的联系,还提供了令人信服的证据,支持PPIC成为黑色素瘤治疗中预测OS的一种有前途的生物标志物。
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来源期刊
Pigment Cell & Melanoma Research
Pigment Cell & Melanoma Research 医学-皮肤病学
CiteScore
8.90
自引率
2.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders
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