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

Tumor discovery Pub Date : 2023-03-24 DOI:10.36922/td.318
Hongyin Sun, Kui Deng, Xin Zhou, Dongsheng Cao, Yong Cheng, Xiang Chen, Mingzhu Yin
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Abstract

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.
一个新的基因预后标志淋巴细胞胞浆蛋白2通过干扰素调节因子5信号通路激活肿瘤浸润的CD8+ t细胞来调节黑色素瘤的进展
皮肤恶性黑色素瘤是最致命的皮肤癌。免疫疗法的出现彻底改变了黑色素瘤的临床治疗现状,给这些患者带来了新的希望。然而,只有一小部分患者有反应。因此,鉴定新的预后和免疫相关生物标志物对指导黑色素瘤临床治疗的发展至关重要。本文利用公共数据库中皮肤黑色素瘤的RNA-seq数据鉴定预后基因特征,发现淋巴细胞胞浆蛋白2 (LCP2)在黑色素瘤患者中高表达,与黑色素瘤预后较好相关。京都基因基因组百科和基因本体分析表明,差异表达基因显著参与溶酶体、b细胞受体信号通路、Fc epsilon RI信号通路和t细胞受体信号通路,表明这些信号通路在黑色素瘤中发挥重要作用。LCP2表达与CD8+ t细胞及黑色素瘤患者总体生存率呈正相关,荧光活化细胞分选实验直接证实了这种正相关关系。体内实验表明,LCP2敲低可显著促进黑色素瘤的进展,降低干扰素调节因子5 (IRF5)的表达。总之,我们发现LCP2可能是黑色素瘤患者无进展生存的预后基因标志,并通过IRF5信号通路激活肿瘤浸润的CD8+ t细胞来调节黑色素瘤的进展,这表明LCP2可以作为免疫治疗的预后生物标志物和治疗靶点。
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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