Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, China.
Aging (Albany NY). 2023 Nov 2;15(21):11918-11939. doi: 10.18632/aging.205157.
Cutaneous melanoma (CM) is widely acknowledged as a highly aggressive form of malignancy that is associated with a considerable degree of morbidity and poor prognosis. Despite this recognition, the precise role of hypoxia-related long noncoding RNAs (HRLs) in the pathogenesis of CM remains an area of active research. This study sought to elucidate the contribution of HRLs in CM by conducting a thorough screening and extraction of hypoxia-related genes (HRGs). In particular, we conducted univariate and multivariate Cox regression analyses to assess the independence of the prognostic signature of HRLs. Our results demonstrated that a novel risk model could be established based on five prognostic HRLs. Remarkably, patients with low-risk scores exhibited significantly higher overall survival rates compared to their high-risk counterparts, as confirmed by Kaplan-Meier survival analysis. Furthermore, we utilized consensus clustering analysis to categorize CM patients into two distinct subtypes, which revealed marked differences in their prognosis and immune infiltration landscapes. Our nomogram results confirmed that the HRLs prognostic signature served as an independent prognostic indicator, offering an accurate evaluation of the survival probability of CM patients. Notably, our findings from ESTIMATE and ssGSEA analyses highlighted significant disparities in the immune infiltration landscape between low- and high-risk groups of CM patients. Additionally, IPS and TIDE results suggested that CM patients in different risk subtypes may exhibit favorable responses to immunotherapy. Enrichment analysis and GSVA results indicated that immune-related signaling pathways may mediate the role of HRLs in CM. Finally, our tumor mutation burden (TMB) results indicated that patients with low-risk scores had a higher TMB status. In summary, the establishment of a risk model based on HRLs in this study provided an accurate prognostic prediction and correlated with the immune infiltration landscape of CM, thereby providing novel insights for the future clinical management of this disease.
皮肤黑色素瘤（CM）被广泛认为是一种高度侵袭性的恶性肿瘤，具有相当高的发病率和较差的预后。尽管如此，缺氧相关长非编码 RNA（HRLs）在 CM 发病机制中的确切作用仍然是一个活跃的研究领域。本研究通过对缺氧相关基因（HRGs）进行全面筛选和提取，旨在阐明 HRLs 在 CM 中的作用。特别是，我们进行了单变量和多变量 Cox 回归分析，以评估 HRLs 预后特征的独立性。我们的研究结果表明，可以基于五个预后 HRLs 建立一个新的风险模型。值得注意的是，低风险评分的患者的总生存率明显高于高风险评分的患者，这一点通过 Kaplan-Meier 生存分析得到了证实。此外，我们利用共识聚类分析将 CM 患者分为两个不同的亚型，这揭示了它们在预后和免疫浸润景观方面的显著差异。我们的列线图结果证实，HRLs 预后特征是一个独立的预后指标，为 CM 患者的生存概率提供了准确的评估。值得注意的是，我们从 ESTIMATE 和 ssGSEA 分析中得出的结果强调了 CM 患者低风险和高风险组之间在免疫浸润景观方面的显著差异。此外，IPS 和 TIDE 结果表明，不同风险亚型的 CM 患者可能对免疫治疗有较好的反应。富集分析和 GSVA 结果表明，免疫相关信号通路可能介导 HRLs 在 CM 中的作用。最后，我们的肿瘤突变负担（TMB）结果表明，低风险评分患者的 TMB 状态更高。总之，本研究建立的基于 HRLs 的风险模型为 CM 提供了准确的预后预测，并与 CM 的免疫浸润景观相关，为该疾病的未来临床管理提供了新的见解。
