AccScience Publishing / TD / Volume 2 / Issue 1 / DOI: 10.36922/td.318

A novel gene prognostic signature lymphocyte cytosolic protein 2 regulates melanoma progression by activating tumor-infiltrating CD8+ T-cells through the interferon regulatory factor 5 signaling pathway

Hongyin Sun1,2,3† Kui Deng4† Xingchen Zhou1,2† Dongsheng Cao5 Yan Cheng6 Xiang Chen1,2* Mingzhu Yin1,2*
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1 Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, China
2 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
3 Department of Pharmacy, Shantou University Medical College, Shantou University, Shantou, China
4 Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Rd, Cloud Town, Hangzhou, China
5 Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China
6 Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China
Tumor Discovery 2023, 2(1), 318
Submitted: 29 December 2022 | Accepted: 27 February 2023 | Published: 24 March 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

Cutaneous malignant melanoma is the most lethal skin cancer. The advent of immunotherapy has revolutionized the status of clinical therapies of melanoma, which brought new hope to these patients. However, only a small proportion of patients are responders. Therefore, the identification of novel prognostic and immune-related biomarkers is crucial to guide the development of melanoma clinical treatments. Herein, RNA-seq data of the cutaneous melanoma from public database were used for identifying prognostic gene signatures, and we found that lymphocyte cytosolic protein 2 (LCP2) was highly expressed in melanoma patient, which was associated with better prognosis for melanoma. Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses demonstrated that the differentially expressed genes are significantly involved in lysosome, B-cell receptor signaling pathways, Fc epsilon RI signaling pathway, and T-cell receptor signaling pathway, indicating that these signaling pathways play important roles in melanoma. LCP2 expression was positively correlated with CD8+ T-cell and the overall survival of melanoma patients, and this positive correlation was directly confirmed by fluorescence-activated cell sorting experiment. The in vivo experiment showed that LCP2 knockdown significantly promoted the melanoma progression and decreased interferon regulatory factor 5 (IRF5) expression. In conclusion, we identified that LCP2 is a possible prognostic gene signature for progression-free survival of melanoma patients and regulates melanoma progression by activating tumor-infiltrating CD8+ T-cells through the IRF5 signaling pathway, indicating that LCP2 could serve as a prognostic biomarker and therapeutic target in immunotherapy.

Cutaneous melanoma
Lymphocyte cytosolic protein 2
Prognostic gene signature
Interferon regulatory factor 5
General Program, the National Natural Science Foundation of China

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Conflict of interest
The authors declare no conflicts of interest.
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Tumor Discovery, Electronic ISSN: 2810-9775 Published by AccScience Publishing