Research Paper|Volume 12, Issue 24|pp 24914—24939

Age-related transcriptome changes in melanoma patients with tumor-positive sentinel lymph nodes

Derek S. Menefee¹, Austin McMasters¹, Jianmin Pan², Xiaohong Li³, Deyi Xiao¹, Sabine Waigel⁴, Wolfgang Zacharias^4,⁵, Shesh N. Rai², Kelly M. McMasters¹, Hongying Hao¹

¹The Hiram C. Polk, Jr., MD. Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA
²Biostatistics and Bioinformatics Facility, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA
³Kentucky Biomedical Research Infrastructure Network Bioinformatics Core, University of Louisville School of Medicine, Louisville, KY 40202, USA
⁴Genomics Facility, University of Louisville School of Medicine, Louisville, KY 40292, USA
⁵Department of Medicine, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA

* Equal contribution

Received: May 28, 2020Accepted: December 9, 2020Published: December 29, 2020

https://doi.org/10.18632/aging.202435

Copyright: © 2020 Menefee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.