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皮肤黑色素瘤中 mA-、mC-和 mA 相关调节因子的预后特征和免疫疗效。

Prognostic signature and immune efficacy of m A-, m C- and m A-related regulators in cutaneous melanoma.

机构信息

Department of Plastic Surgery of Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

Department of Plastic Surgery of Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

J Cell Mol Med. 2021 Sep;25(17):8405-8418. doi: 10.1111/jcmm.16800. Epub 2021 Jul 21.

Abstract

Cutaneous melanoma (CM) is an aggressive cancer; given that initial and specific signs are lacking, diagnosis is often late and the prognosis is poor. RNA modification has been widely studied in tumour progression. Nevertheless, little progress has been made in the signature of N -methyladenosine (m A), 5-methylcytosine (m C), N -methyladenosine (m A)-related regulators and the tumour microenvironment (TME) cell infiltration in CM. Our study identified the characteristics of m A-, m C- and m A-related regulators based on 468 CM samples from the public database. Using univariate, multivariate and LASSO Cox regression analysis, a risk model of regulators was established and validated by a nomogram on independent prognostic factors. The gene set variation analysis (GSVA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) clarified the involved functional pathways. A combined single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT approach revealed TME of regulator-related prognostic signature. The nine-gene signature stratified the patients into distinct risk subgroups for personalized prognostic assessment. Additionally, functional enrichment, immune infiltration and immunotherapy response analysis indicated that the high-risk group was correlated with T-cell suppression, while the low-risk group was more sensitive to immunotherapy. The findings presented here contribute to our understanding of the TME molecular heterogeneity in CM. Nine m A-, m C- and m A-related regulators may also be promising biomarkers for future research.

摘要

皮肤黑色素瘤(CM)是一种侵袭性癌症;由于缺乏初始和特定的迹象,诊断通常较晚,预后较差。RNA 修饰在肿瘤进展中得到了广泛的研究。然而,在 CM 中,N6-甲基腺苷(m A)、5-甲基胞嘧啶(m C)、m A 相关调节剂和肿瘤微环境(TME)细胞浸润的特征方面几乎没有取得进展。我们的研究基于公共数据库中的 468 个 CM 样本,确定了 m A、m C 和 m A 相关调节剂的特征。使用单变量、多变量和 LASSO Cox 回归分析,建立了一个基于独立预后因素的调节因子风险模型,并通过列线图进行了验证。基因集变异分析(GSVA)和京都基因与基因组百科全书(KEGG)阐明了涉及的功能途径。综合单样本基因集富集分析(ssGSEA)和 CIBERSORT 方法揭示了与调节因子相关预后特征的 TME。该九基因特征将患者分为不同的风险亚组,用于个性化预后评估。此外,功能富集、免疫浸润和免疫治疗反应分析表明,高危组与 T 细胞抑制有关,而低危组对免疫治疗更敏感。本研究结果有助于我们了解 CM 中 TME 的分子异质性。九个 m A、m C 和 m A 相关调节剂也可能成为未来研究的有前途的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4a/8419166/61a3e8cbe655/JCMM-25-8405-g008.jpg

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