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单细胞 RNA 测序揭示了甲下和足底黑色素瘤之间的肿瘤异质性和免疫微环境。

Single-cell RNA sequencing unveils tumor heterogeneity and immune microenvironment between subungual and plantar melanoma.

机构信息

Fourth Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.

Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou, China.

出版信息

Sci Rep. 2024 Mar 25;14(1):7039. doi: 10.1038/s41598-024-57640-8.

DOI:10.1038/s41598-024-57640-8
PMID:38528036
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10963724/
Abstract

Acral melanoma (AM) is a subtype of melanoma with high prevalence in East Asians. AM is characterized by greater aggressiveness and lower survival rates. However, there are still fewer studies on immune mechanisms of AM especially subungual melanoma (SM) versus non-subungual melanoma (NSM). In order to explore tumor heterogeneity and immune microenvironment in different subtypes of AM, we applied single-cell RNA sequencing to 24,789 single cells isolated from the SM and plantar melanoma (PM) patients. Aspects of tumor heterogeneity, melanocytes from PM and SM had significant differences in gene expression, CNV and pathways in which tumor-associated such as NF-kb and Wnt were involved. Regarding the immune microenvironment, PM contained more fibroblasts and T/NK cells. The EPHA3-EFNA1 axis was expressed only in cancer-associated fibroblast (CAF) and melanocytes of PM, and the TIGIT-NECTIN2 axis was expressed in both AM subtypes of T/NK cells and melanocytes. Altogether, our study helps to elucidate the tumor heterogeneity in AM subpopulations and provides potential therapeutic targets for clinical research.

摘要

肢端黑色素瘤（AM）是一种黑色素瘤亚型，在东亚地区发病率较高。AM 的特点是侵袭性更强，生存率更低。然而，针对 AM 的免疫机制，特别是亚甲黑素瘤（SM）与非亚甲黑素瘤（NSM）的研究仍然较少。为了探索不同 AM 亚型中的肿瘤异质性和免疫微环境，我们对 24789 个来自 SM 和足底黑素瘤（PM）患者的单细胞进行了单细胞 RNA 测序。在肿瘤异质性方面，PM 和 SM 的黑色素细胞在基因表达、CNV 和肿瘤相关途径（如 NF-kb 和 Wnt）方面存在显著差异。在免疫微环境方面，PM 含有更多的成纤维细胞和 T/NK 细胞。EPHA3-EFNA1 轴仅在 PM 的癌相关成纤维细胞（CAF）和黑色素细胞中表达，而 TIGIT-NECTIN2 轴在 AM 的 T/NK 细胞和黑色素细胞亚型中均有表达。总的来说，我们的研究有助于阐明 AM 亚群中的肿瘤异质性，并为临床研究提供潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/0662414e9bf8/41598_2024_57640_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/0cd7296d5b16/41598_2024_57640_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/b1f413e97dc8/41598_2024_57640_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/e2632fc66f79/41598_2024_57640_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/2720d7bdb4dc/41598_2024_57640_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/ca19a7fec5ac/41598_2024_57640_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/0662414e9bf8/41598_2024_57640_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/0cd7296d5b16/41598_2024_57640_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/b1f413e97dc8/41598_2024_57640_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/e2632fc66f79/41598_2024_57640_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/2720d7bdb4dc/41598_2024_57640_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/ca19a7fec5ac/41598_2024_57640_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18c/10963724/0662414e9bf8/41598_2024_57640_Fig6_HTML.jpg

相似文献

[1]
Single-cell RNA sequencing unveils tumor heterogeneity and immune microenvironment between subungual and plantar melanoma.

Sci Rep. 2024-3-25

[2]
Mapping the single-cell landscape of acral melanoma and analysis of the molecular regulatory network of the tumor microenvironments.

Elife. 2022-7-27

[3]
Prognostic value of genetic aberrations and tumor immune microenvironment in primary acral melanoma.

J Transl Med. 2023-2-4

[4]
Melanomas of the palm, sole, and nailbed: a clinicopathologic study.

Cancer. 1980-12-1

[5]
Hyperplastic melanocytes with chromosomal aberrations in surrounding skin of subungual melanoma: fluorescence in situ hybridisation analysis using whole-slide digital imaging.

Histopathology. 2022-12

[6]
Scattered atypical melanocytes with hyperchromatic nuclei in the nail matrix: diagnostic clue for early subungual melanoma in situ.

J Cutan Pathol. 2016-1

[7]
Prognostic Significance of Subungual Anatomic Site in Acral Lentiginous Melanoma.

Arch Pathol Lab Med. 2021-8-1

[8]
Identification of tumor-intrinsic drivers of immune exclusion in acral melanoma.

J Immunother Cancer. 2023-10

[9]
Early malignant melanoma manifested as longitudinal melanonychia: subungual melanoma may arise from suprabasal melanocytes.

Br J Dermatol. 2000-8

[10]
Acral lentiginous melanoma: Basic facts, biological characteristics and research perspectives of an understudied disease.

Pigment Cell Melanoma Res. 2021-1

引用本文的文献

[1]
The malignant signature gene of cancer-associated fibroblasts serves as a potential prognostic biomarker for colon adenocarcinoma patients.

Front Immunol. 2025-4-17

[2]
Single-cell transcriptomic landscape deciphers intratumoral heterogeneity and subtypes of acral and mucosal melanoma.

Clin Cancer Res. 2025-4-7

本文引用的文献

[1]
ERK hyperactivation serves as a unified mechanism of escape in intrinsic and acquired CDK4/6 inhibitor resistance in acral lentiginous melanoma.

Oncogene. 2024-2

[2]
Identification of tumor-intrinsic drivers of immune exclusion in acral melanoma.

J Immunother Cancer. 2023-10

[3]
Inhibition of EphA3 Expression in Tumour Stromal Cells Suppresses Tumour Growth and Progression.

Cancers (Basel). 2023-9-20

[4]
TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation.

Nat Commun. 2023-8-18

[5]
TIGIT, a novel immune checkpoint therapy for melanoma.

Cell Death Dis. 2023-7-26

[6]
The Ephrin tyrosine kinase a3 (EphA3) is a novel mediator of RAGE-prompted motility of breast cancer cells.

J Exp Clin Cancer Res. 2023-7-12

[7]
Studying TIGIT activity against tumors through the generation of knockout mice.

Oncoimmunology. 2023

[8]
Single-cell Characterization of the Cellular Landscape of Acral Melanoma Identifies Novel Targets for Immunotherapy.

Clin Cancer Res. 2022-5-13

[9]
Single-cell RNA sequencing reveals cell heterogeneity and transcriptome profile of breast cancer lymph node metastasis.

Oncogenesis. 2021-10-5

[10]
Activation of Fibroblasts in Skin Cancer.

J Invest Dermatol. 2022-4

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