Supplementary Material for: Tropomyosin-Related Kinase Receptor and Neurotrophin Expression in Cutaneous Melanoma Is Associated with a Poor Prognosis and Decreased Survival

<b><i>Objective:</i></b> Normally, activation of tropomyosin-related kinase (TRK) receptors by neurotrophins (NTs) stimulates intracellular pathways involved in cell survival and proliferation. Dysregulation of NT/TRK signaling may affect neoplasm prognosis. Data on NT and TRK expression in melanomas are limited, and it is unclear whether NT/TRK signaling pathways are involved in the origin and progression of this neoplasm. <b><i>Methods:</i></b> We examined whether NT/TRK expression differs across different cutaneous melanoma grades and subtypes, and whether it is associated with melanoma prognosis and survival. A cross-sectional study was performed in which the expression of TrkA, TrkB, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) was analyzed by immunohistochemistry of 154 melanoma samples. We investigated NT/TRK expression associations with prognostic factors for melanoma, relapse-free survival (RFS), and overall survival (OS). <b><i>Results:</i></b> Of the 154 melanoma samples, 77 (55.4%) were TrkA immunopositive, 81 (58.3%) were TrkB immunopositive, 113 (81.3%) were BDNF immunopositive, and 104 (75.4%) were NGF immunopositive. We found NT/TRK expression associated strongly with several clinical prognostic factors, including the tumor-node-metastasis stage (<i>p</i> &lt; 0.001), histological subtype (<i>p</i> &lt; 0.001), and Clark level (<i>p</i> &lt; 0.05), as well as with a worse OS (<i>p</i> &lt; 0.05 for all, except TrkB) and RFS (<i>p</i> &lt; 0.05 for all). <b><i>Conclusions:</i></b> Our results show strong associations of NT/TRK expression with melanoma stage progression and a poor prognosis.

<b><i>研究目的：</i></b> 正常情况下，神经营养因子（neurotrophins, NTs）激活原肌球蛋白受体激酶（tropomyosin-related kinase, TRK）后，可刺激参与细胞存活与增殖的细胞内通路。神经营养因子/TRK信号通路失调可能影响肿瘤预后。目前关于黑色素瘤中神经营养因子与TRK表达的相关数据较为有限，且尚不清楚神经营养因子/TRK信号通路是否参与该肿瘤的起源与进展。
<b><i>研究方法：</i></b> 本研究旨在探讨神经营养因子/TRK的表达在不同皮肤黑色素瘤分级与亚型之间是否存在差异，以及其与黑色素瘤预后及生存情况的相关性。本研究采用横断面研究设计，通过免疫组化方法检测154例黑色素瘤样本中TrkA、TrkB、神经生长因子（nerve growth factor, NGF）以及脑源性神经营养因子（brain-derived neurotrophic factor, BDNF）的表达水平。我们分析了神经营养因子/TRK表达与黑色素瘤预后因素、无复发生存期（relapse-free survival, RFS）以及总生存期（overall survival, OS）的关联。
<b><i>研究结果：</i></b> 在154例黑色素瘤样本中，77例（55.4%）呈TrkA免疫阳性，81例（58.3%）呈TrkB免疫阳性，113例（81.3%）呈BDNF免疫阳性，104例（75.4%）呈NGF免疫阳性。我们发现神经营养因子/TRK的表达与多项临床预后因素显著相关，包括肿瘤-淋巴结-转移分期（<i>p</i> < 0.001）、组织学亚型（<i>p</i> < 0.001）以及克拉克分级（<i>p</i> < 0.05）；同时其表达还与更差的总生存期（除TrkB外，所有指标<i>p</i> < 0.05）以及无复发生存期（所有指标<i>p</i> < 0.05）相关。
<b><i>研究结论：</i></b> 本研究结果显示，神经营养因子/TRK的表达与黑色素瘤分期进展及不良预后存在显著关联。