Research Paper Volume 12, Issue 24 pp 24914—24939
Age-related transcriptome changes in melanoma patients with tumor-positive sentinel lymph nodes
- 1 The Hiram C. Polk, Jr., MD. Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA
- 2 Biostatistics and Bioinformatics Facility, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA
- 3 Kentucky Biomedical Research Infrastructure Network Bioinformatics Core, University of Louisville School of Medicine, Louisville, KY 40202, USA
- 4 Genomics Facility, University of Louisville School of Medicine, Louisville, KY 40292, USA
- 5 Department of Medicine, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA
Received: May 28, 2020 Accepted: December 9, 2020 Published: December 29, 2020
https://doi.org/10.18632/aging.202435How to Cite
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.
Abbreviations
CI: Confidence interval; DEGs: Differentially expressed genes; FC: Fold changes; FCO: Fold change outlier; FOS: FBJ murine osteosarcoma viral oncogene homolog; GEO: Gene Expression Omnibus; IRAK3: Interleukin-1 receptor-associated kinase 3; ITGB1: Integrin subunit beta 1; ITGBL1: Integrin subunit beta like 1; NR4A2: Nuclear receptor subfamily 4, group A, member 2; PPAR: Peroxisome proliferator-activated receptor; QC/QA: Quality control/quantity assessment; qRT-PCR: Quantitative reverse transcriptase polymerase chain reaction; recurno: Without recurrence; recuryes: Recurrence; SLN: Sentinel lymph node; SMT: Sunbelt melanoma trial; TERT: Telomerase reverse transcriptase; Tregs: T regulatory cells; yr60-: <60 years old; yr60+: ≥60 years old.