The Hiram C. Polk, Jr., MD. Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Biostatistics and Bioinformatics Facility, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Aging (Albany NY). 2020 Dec 29;12(24):24914-24939. doi: 10.18632/aging.202435.
Age is an important factor for determining the outcome of melanoma patients. Sentinel lymph node (SLN) status is also a strong predictor of survival for melanoma. Paradoxically, older melanoma patients have a lower incidence of SLN metastasis but a higher mortality rate when compared with their younger counterparts. The mechanisms that underlie this phenomenon remain unknown. This study uses three independent datasets of RNA samples from patients with melanoma metastatic to the SLN to identify age-related transcriptome changes in SLNs and their association with outcome. Microarray was applied to the first dataset of 97 melanoma patients. NanoString was performed in the second dataset to identify the specific immune genes and pathways that are associated with recurrence in younger versus older patients. qRT-PCR analysis was used in the third dataset of 36 samples to validate the differentially expressed genes (DEGs) from microarray and NanoString. These analyses show that FOS, NR4A, and ITGB1 genes were significantly higher in older melanoma patients with positive SLNs. IRAK3- and Wnt10b-related genes are the major pathways associated with recurrent melanoma in younger and older patients with tumor-positive SLNs, respectively. This study aims to elucidate age-related differences in SLNs in the presence of nodal metastasis.
年龄是决定黑色素瘤患者预后的一个重要因素。前哨淋巴结（SLN）状态也是黑色素瘤患者生存的有力预测指标。矛盾的是，与年轻患者相比，老年黑色素瘤患者 SLN 转移的发生率较低，但死亡率较高。其背后的机制尚不清楚。本研究使用黑色素瘤转移至 SLN 的患者的三个独立 RNA 样本数据集，以确定 SLN 中与年龄相关的转录组变化及其与预后的关系。对第一个 97 名黑色素瘤患者的数据集进行了微阵列分析。在第二个数据集，采用 NanoString 技术确定与年轻和老年患者复发相关的特定免疫基因和途径。对第三个数据集的 36 个样本进行 qRT-PCR 分析，以验证微阵列和 NanoString 中差异表达的基因（DEGs）。这些分析表明，在 SLN 阳性的老年黑色素瘤患者中，FOS、NR4A 和 ITGB1 基因明显较高。IRAK3 和 Wnt10b 相关基因分别是与 SLN 阳性的年轻和老年患者复发性黑色素瘤相关的主要途径。本研究旨在阐明存在淋巴结转移时 SLN 中的年龄相关差异。
