Meng Jinzhi, Huang Xing, Qiu Yue, Yu Miao, Lu Jinfeng, Yao Jun
Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.
Int J Gen Med. 2021 Sep 7;14:5345-5361. doi: 10.2147/IJGM.S328522. eCollection 2021.
Skin cutaneous melanoma (SKCM) is the most malignant tumor among skin cancers. Immunotherapy has shown a great role in the advantageous prognosis of SKCM. However, only a small percentage of people can benefit from immunotherapy. To date, there has been insufficient evidence to reveal the prognostic value of m6A in SKCM and its relationship with the infiltration of immune cells and the efficacy of immunotherapy.
Here, we synthetically analyzed 23 m6A regulators from SKCM samples collected from the TCGA and GEO databases. We defined three m6A modification patterns and constructed m6A scores using principal component analysis (PCA).
We found significant differences in overall survival (OS) and immune infiltration between different m6A subclusters. Besides, m6A score was positively correlated with regulatory T-cell and helper T-cell content, which may account for the association of high m6A scores with superior prognosis. Multivariate Cox regression analysis revealed that the m6A score was an independent prognostic indicator. Moreover, patients with high m6A scores showed a better response to immunotherapy, and this result was further validated in two independent immunotherapy cohorts receiving anti-PD-1/PD-L1 therapy.
The findings suggested the m6A score can screen suitable candidates for immunotherapy and can predict immunotherapy response. This analysis of different m6A patterns in a large sample of SKCM expanded our understanding of TME and provided new ideas for prognostic assessment and personalized immunotherapy strategies for SKCM patients.
皮肤黑色素瘤（SKCM）是皮肤癌中最恶性的肿瘤。免疫疗法在SKCM的良好预后中发挥了重要作用。然而，只有一小部分人能从免疫疗法中获益。迄今为止，尚无足够证据揭示m6A在SKCM中的预后价值及其与免疫细胞浸润和免疫疗法疗效的关系。
在此，我们综合分析了从TCGA和GEO数据库收集的SKCM样本中的23种m6A调节因子。我们定义了三种m6A修饰模式，并使用主成分分析（PCA）构建了m6A评分。
我们发现不同m6A亚群之间的总生存期（OS）和免疫浸润存在显著差异。此外，m6A评分与调节性T细胞和辅助性T细胞含量呈正相关，这可能解释了高m6A评分与较好预后之间的关联。多变量Cox回归分析显示，m6A评分是一个独立的预后指标。此外，m6A评分高的患者对免疫疗法表现出更好的反应，这一结果在两个接受抗PD-1/PD-L1治疗的独立免疫疗法队列中得到了进一步验证。
研究结果表明，m6A评分可以筛选出适合免疫疗法的患者，并能预测免疫疗法的反应。对大量SKCM样本中不同m6A模式的分析扩展了我们对肿瘤微环境的理解，并为SKCM患者的预后评估和个性化免疫治疗策略提供了新的思路。
