Hypoxic transcriptomes predict survival and tumor-infiltrating immune cell composition in cutaneous melanoma.

IF 1.5 4区 医学 Q3 DERMATOLOGY
Melanoma Research Pub Date : 2024-04-01 Epub Date: 2024-02-07 DOI:10.1097/CMR.0000000000000938
Michael J Diaz, Jessica Quach, Joanna Song, Silvija Milanovic, Jasmine T Tran, Lauren C Ladehoff, Sai Batchu, Patrick Whitman, Benajmin H Kaffenberger, Marjorie E Montanez-Wiscovich
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引用次数: 0

Abstract

Hypoxia has established associations with aggressive tumor phenotypes in many cancers. However, it is not currently understood whether tumor hypoxia levels map to distinct immune infiltrates in cutaneous melanoma, potentially unveiling novel therapeutic targets. To this end, we leveraged a previously identified seven-gene hypoxia signature to grade hypoxia levels of 460 cutaneous melanomas obtained from the Broad Institute GDAC Firehose portal. CIBERSORTx ( https://cibersortx.stanford.edu/ ) was employed to calculate the relative abundance of 22 mature human hematopoietic populations. Clinical outcomes and immune cell associations were assessed by computational means. Results indicated that patients with high-hypoxia tumors reported significantly worse overall survival and correlated with greater Breslow depth, validating the in-silico methodology. High-hypoxia tumors demonstrated increased infiltration of activated and resting dendritic cells, resting mast cells, neutrophils, and resting NK cells, but lower infiltration of gamma-delta T cells. These data suggest that high tumor hypoxia correlates with lower survival probability and distinct population differences of several tumor-infiltrating leukocytes in cutaneous melanomas.

缺氧转录组预测皮肤黑色素瘤的存活率和肿瘤浸润免疫细胞的组成。
缺氧与许多癌症的侵袭性肿瘤表型有关。然而,目前还不清楚肿瘤缺氧水平是否与皮肤黑色素瘤中不同的免疫浸润相关,从而可能揭示新的治疗靶点。为此,我们利用先前确定的七基因缺氧特征对从布罗德研究所 GDAC Firehose 门户网站获得的 460 例皮肤黑色素瘤的缺氧水平进行了分级。CIBERSORTx (https://cibersortx.stanford.edu/) 被用来计算 22 种成熟人类造血群体的相对丰度。通过计算手段评估了临床结果和免疫细胞关联。结果表明,高缺氧肿瘤患者的总生存率明显较低,且与布瑞斯洛深度相关,验证了室内方法学。高缺氧肿瘤显示活化和静止树突状细胞、静止肥大细胞、中性粒细胞和静止NK细胞浸润增加,但γ-δT细胞浸润较低。这些数据表明,肿瘤高缺氧与皮肤黑色素瘤较低的存活几率和几种肿瘤浸润白细胞明显的种群差异有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Melanoma Research
Melanoma Research 医学-皮肤病学
CiteScore
3.40
自引率
4.50%
发文量
139
审稿时长
6-12 weeks
期刊介绍: ​​​​​​Melanoma Research is a well established international forum for the dissemination of new findings relating to melanoma. The aim of the Journal is to promote the level of informational exchange between those engaged in the field. Melanoma Research aims to encourage an informed and balanced view of experimental and clinical research and extend and stimulate communication and exchange of knowledge between investigators with differing areas of expertise. This will foster the development of translational research. The reporting of new clinical results and the effect and toxicity of new therapeutic agents and immunotherapy will be given emphasis by rapid publication of Short Communications. ​Thus, Melanoma Research seeks to present a coherent and up-to-date account of all aspects of investigations pertinent to melanoma. Consequently the scope of the Journal is broad, embracing the entire range of studies from fundamental and applied research in such subject areas as genetics, molecular biology, biochemistry, cell biology, photobiology, pathology, immunology, and advances in clinical oncology influencing the prevention, diagnosis and treatment of melanoma.
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