鉴定转移性皮肤黑色素瘤中与代谢相关的基因组特征,用于预后和免疫治疗效果的评估。

Identification of a metabolism-linked genomic signature for prognosis and immunotherapeutic efficiency in metastatic skin cutaneous melanoma.

机构信息

Department of Oral and Maxillofacial Surgery, Kunming Medical University School and Hospital of Stomatology, Kunming, China.

Yunnan Key Laboratory of Stomatology, Kunming, China.

出版信息

Medicine (Baltimore). 2024 Jun 7;103(23):e38347. doi: 10.1097/MD.0000000000038347.

Abstract

Metastatic skin cutaneous melanoma (MSCM) is the most rapidly progressing/invasive skin-based malignancy, with median survival rates of about 12 months. It appears that metabolic disorders accelerate disease progression. However, correlations between metabolism-linked genes (MRGs) and prognosis in MSCM are unclear, and potential mechanisms explaining the correlation are unknown. The Cancer Genome Atlas (TCGA) was utilized as a training set to develop a genomic signature based on the differentially expressed MRGs (DE-MRGs) between primary skin cutaneous melanoma (PSCM) and MSCM. The Gene Expression Omnibus (GEO) was utilized as a validation set to verify the effectiveness of genomic signature. In addition, a nomogram was established to predict overall survival based on genomic signature and other clinic-based characteristics. Moreover, this study investigated the correlations between genomic signature and tumor micro-environment (TME). This study established a genomic signature consisting of 3 genes (CD38, DHRS3, and TYRP1) and classified MSCM patients into low and high-risk cohorts based on the median risk scores of MSCM cases. It was discovered that cases in the high-risk cohort had significantly lower survival than cases in the low-risk cohort across all sets. Furthermore, a nomogram containing this genomic signature and clinic-based parameters was developed and demonstrated high efficiency in predicting MSCM case survival times. Interestingly, Gene Set Variation Analysis results indicated that the genomic signature was involved in immune-related physiological processes. In addition, this study discovered that risk scoring was negatively correlated with immune-based cellular infiltrations in the TME and critical immune-based checkpoint expression profiles, indicating that favorable prognosis may be influenced in part by immunologically protective micro-environments. A novel 3-genomic signature was found to be reliable for predicting MSCM outcomes and may facilitate personalized immunotherapy.

摘要

转移性皮肤黑色素瘤(MSCM)是最具侵袭性和进展最快的皮肤恶性肿瘤,中位生存时间约为 12 个月。代谢紊乱似乎会加速疾病的进展。然而,代谢相关基因(MRGs)与 MSCM 预后之间的相关性尚不清楚,潜在的解释相关性的机制也不清楚。本研究利用癌症基因组图谱(TCGA)作为训练集,基于原发性皮肤黑色素瘤(PSCM)和 MSCM 之间差异表达的 MRGs(DE-MRGs),开发了基于基因组特征的基因签名。利用基因表达综合数据库(GEO)作为验证集,验证基因组特征的有效性。此外,还建立了一个列线图,根据基因组特征和其他临床特征预测总生存期。此外,本研究还探讨了基因组特征与肿瘤微环境(TME)之间的相关性。本研究建立了一个由 3 个基因(CD38、DHRS3 和 TYRP1)组成的基因组特征,并根据 MSCM 病例的中位风险评分,将 MSCM 患者分为低风险和高风险队列。结果发现,在所有队列中,高风险队列的病例的生存时间明显低于低风险队列的病例。此外,建立了一个包含该基因组特征和临床参数的列线图,该图在预测 MSCM 病例的生存时间方面表现出了较高的效率。有趣的是,基因集变异分析结果表明,该基因组特征与免疫相关的生理过程有关。此外,本研究还发现,风险评分与 TME 中的免疫细胞浸润和关键免疫检查点表达谱呈负相关,这表明有利的预后可能部分受到免疫保护微环境的影响。本研究发现了一个新的 3 个基因组特征,可用于预测 MSCM 患者的预后,为个性化免疫治疗提供了可能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c15/11155616/a4a65cb8b237/medi-103-e38347-g001.jpg

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