Wang Ronglin, Guo Yongdong, Ma Peixiang, Song Yang, Min Jie, Zhao Ting, Hua Lei, Zhang Chao, Yang Cheng, Shi Jingjie, Zhu Liaoliao, Gan Dongxue, Li Shanshan, Li Junqiang, Su Haichuan
Department of Oncology, Tangdu Hospital, Air Force Medical University, Xi'an, China.
Front Oncol. 2022 Mar 31;12:851766. doi: 10.3389/fonc.2022.851766. eCollection 2022.
Pancreatic adenocarcinoma (PAAD) is one of the most malignant cancers and has a poor prognosis. As a critical RNA modification, 5-methylcytosine (mC) has been reported to regulate tumor progression, including PAAD progression. However, a comprehensive analysis of mC regulators in PAAD is lacking.
In the present study, PAAD datasets were obtained from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and ArrayExpress databases. The expression pattern of mC regulators were analyzed and patients were divided into different mC clusters according to consensus clustering based on mC regulators. Additionally, mC differentially expressed genes (DEGs) were determined using Limma package. Based on mC DEGs, patients were divided into mC gene clusters. Moreover, mC gene signatures were derived from mC DEGs and a quantitative indicator, the mC score, was developed from the mC gene signatures.
Our study showed that mC regulators were differentially expressed in patients with PAAD. The mC clusters and gene clusters based on mC regulators and mC DEGs were related to immune cell infiltration, immune-related genes and patient survival status, indicating that mC modification play a central role in regulating PAAD development partly by modulating immune microenvironment. Additionally, a quantitative indicator, the mC score, was also developed and was related to a series of immune-related indicators. Moreover, the mC score precisely predicted the immunotherapy response and prognosis of patients with PAAD.
In summary, we confirmed that mC regulators regulate PAAD development by modulating the immune microenvironment. In addition, a quantitative indicator, the mC score, was developed to predict immunotherapy response and prognosis and assisted in identifying PAAD patients suitable for tailored immunotherapy strategies.
胰腺腺癌（PAAD）是最具侵袭性的癌症之一，预后较差。作为一种关键的RNA修饰，5-甲基胞嘧啶（mC）已被报道可调节肿瘤进展，包括PAAD进展。然而，目前缺乏对PAAD中mC调节剂的全面分析。
在本研究中，从基因表达综合数据库（GEO）、癌症基因组图谱（TCGA）、国际癌症基因组联盟（ICGC）和ArrayExpress数据库中获取PAAD数据集。分析mC调节剂的表达模式，并根据基于mC调节剂的一致性聚类将患者分为不同的mC簇。此外，使用Limma软件包确定mC差异表达基因（DEG）。基于mC DEG，将患者分为mC基因簇。此外，从mC DEG中得出mC基因特征，并从mC基因特征中开发出一个定量指标，即mC评分。
我们的研究表明，mC调节剂在PAAD患者中差异表达。基于mC调节剂和mC DEG的mC簇和基因簇与免疫细胞浸润、免疫相关基因和患者生存状态相关，表明mC修饰部分通过调节免疫微环境在PAAD发展中起核心作用。此外，还开发了一个定量指标，即mC评分，它与一系列免疫相关指标相关。此外，mC评分准确预测了PAAD患者的免疫治疗反应和预后。
总之，我们证实mC调节剂通过调节免疫微环境来调节PAAD的发展。此外，还开发了一个定量指标，即mC评分，以预测免疫治疗反应和预后，并有助于识别适合定制免疫治疗策略的PAAD患者。
