Development and validation of a tissue-based DNA methylation risk-score model to predict the prognosis of surgically resected pancreatic cancer patients.
Development and validation of a tissue-based DNA methylation risk-score model to predict the prognosis of surgically resected pancreatic cancer patients.
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开发和验证基于组织的 DNA 甲基化风险评分模型，以预测手术切除的胰腺癌患者的预后
DOI：
10.21037/gs-22-517
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发表时间：
2022-10
期刊：
影响因子：
1.8
通讯作者：
Zhang, Zixiang
中科院分区：
文献类型：
--
作者：
Yang, Jian;Tang, Yuchen;Wang, Jie;Yu, Chengqing;Li, Haoran;Li, Ye;Zhou, Jian;Zhang, Zixiang;Zhang, Zixiang
背景胰腺癌（PC）是一种高度恶性的肿瘤，生存率低.预测手术切除的PC患者的生存率具有挑战性。预后分期工具可能有助于指导治疗，也有助于治疗后监测。本研究旨在建立基于组织的DNA甲基化风险评分模型，以预测胰腺癌手术切除患者的预后。方法对苏州大学附属第一医院50例I~II期胰腺癌患者进行单中心回顾性研究。从每个患者获得肿瘤和邻近的正常组织，并进行基于捕获的靶向甲基化分析。结果肿瘤组织与癌旁远距离组织相比，共有1,162个DNA甲基化区块（DMBs）发生了差异甲基化（P <0.05）。最小绝对收缩和选择算子（LASSO）和逐步回归分析揭示了甲基化特征（风险评分）和总生存期（OS）之间的显著相关性。在生存分析中，高风险组患者的OS显著低于低风险组患者[P ≤ 0.001; 1年时的曲线下面积（AUC）为0.789; 2年时的AUC为0.852]。还使用来自癌症基因组图谱胰腺导管腺癌（TCGA-PDAC）数据集的166名PC患者的临床和甲基化数据来验证风险评分。高风险组患者的OS显著低于低风险组（P = 0.004; 1年时的AUC，0.677; 3年时的AUC，0.611）。当考虑临床参数时，风险评分是考克斯回归分析中唯一的独立预后参数（P <0.001）。此外，低风险患者的免疫浸润水平较高，抗肿瘤免疫激活，对吉西他滨和紫杉醇的敏感性增加。相比之下，高风险患者的KRAS突变率较低，从顺铂中获益更多。结论在我们的研究中，我们构建并验证了一个基于组织的DNA甲基化风险评分模型，以预测预后并识别手术时具有高死亡风险的PC患者。该模型可能为临床医生提供一种基于组织的预后评估工具，以帮助他们做出治疗决策。
Background Pancreatic cancer (PC) is a highly malignant tumor associated with low survival rates. It is challenging to predict the survival of surgically resected patients with PC. A prognostic staging tool could be beneficial to guide treatments and also aid post-treatment surveillance. This study aimed to identify tissue-based DNA methylation risk-score model to predict the prognosis of surgically resected pancreatic cancer patients. Methods We performed a monocentric, retrospective study that included 50 patients with stage I–II PC from The First Affiliated Hospital of Soochow University (SU cohort). Both tumor and adjacent normal tissues were obtained from each patient and subjected to capture-based targeted methylation profiling. Results In total, 1,162 DNA methylation blocks (DMBs) were differentially methylated in tumor tissues compared with adjacent long-distance tissues (P<0.05). Least Absolute Shrinkage and Selection Operator (LASSO) and stepwise regression analyses revealed a significant correlation between the methylation signature (risk score) and overall survival (OS). Patients in the high-risk group showed significantly poorer OS than those in the low-risk group in the survival analysis [P≤0.001; area under curve (AUC) at 1 year, 0.789; AUC at 2 years, 0.852]. The risk score was also validated using clinical and methylation data of 166 PC patients from The Cancer Genome Atlas pancreatic ductal adenocarcinoma (TCGA-PDAC) dataset. Patients in the high-risk group showed significantly poorer OS than those in the low-risk group (P=0.004; AUC at 1 years, 0.677; AUC at 3 years, 0.611). When clinical parameters were considered, the risk score was the only independent prognostic parameter (P<0.001) in the Cox regression analysis. Furthermore, low-risk patients had higher levels of immune infiltration, anti-tumor immune activation, and increased sensitivity to gemcitabine and paclitaxel. In contrast, high-risk patients had lower KRAS mutation rates and benefited more from cisplatin. Conclusions In our study, we constructed and validated a tissue-based DNA methylation risk-score model to predict prognosis and identify PC patients with a high mortality risk at the time of surgery. This model might provide a tissue-based prognostic assessment tool for clinicians to aid their treatment decision-making.
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影响因子：
3.1
作者：
Cui, Xian-Ping;Qin, Cheng-Kun;Tian, Xing-Song
通讯作者：
Tian, Xing-Song
影响因子：
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作者：
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影响因子：
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影响因子：
78.8
作者：
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通讯作者：
van Engeland, Manon
影响因子：
3.2
作者：
Ferrone, Cristina R.;Brennan, Murray F.;Allen, Peter J.
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