Table1_Type 1 T Helper Cell-Based Molecular Subtypes and Signature Are Associated with Clinical Outcome in Pancreatic Ductal Adenocarcinoma.docx

Lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC) is shown to be related with poor prognosis. To construct an immune-related gene prognostic risk model for PDAC and clarify the molecular and immune characteristics and the benefit of immune checkpoint inhibitor (ICI) therapy in prognostic risk model-defined subgroups of PDAC, we analyze the association between the density of immune cell infiltration and lymph node metastatic status and further study the potential role of immune cells, immune cell–related genes, and immunotherapy outcomes in PDAC patients using bioinformatics models and machine learning methods. Based on The Cancer Genome Atlas (TCGA), PACA-AU and PACA-CA data sets, 62 immune-related hub genes were identified by weighted gene co-expression network analysis (WGCNA). Four genes were selected to construct a molecular subtype identification based on the type 1 T helper cell–related hub genes by using the Cox regression method. We found that lower type 1 T helper cell abundance was correlated with prolonged survival in PDAC patients. Further, prognostic risk score model constructed with the type 1 T helper cell-related signature showed high accuracy in predicting overall survival and response to immunotherapy. This study might improve the understanding of the role of type 1 T helper cells in PDAC patients and aid in the development of immunotherapy and personalized treatments for these patients.

胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）的淋巴结转移已被证实与不良预后相关。为构建胰腺导管腺癌的免疫相关基因预后风险模型，并明确其分子与免疫特征，以及该预后风险模型划分的胰腺导管腺癌亚群的免疫检查点抑制剂（immune checkpoint inhibitor, ICI）治疗获益情况，我们分析了免疫细胞浸润密度与淋巴结转移状态之间的关联，并进一步借助生物信息学模型与机器学习方法，探究免疫细胞、免疫细胞相关基因以及免疫治疗结局在胰腺导管腺癌患者中的潜在作用。基于癌症基因组图谱（The Cancer Genome Atlas, TCGA）、PACA-AU及PACA-CA数据集，我们通过加权基因共表达网络分析（weighted gene co-expression network analysis, WGCNA）筛选出62个免疫相关核心基因。利用Cox回归法，基于1型辅助性T细胞（type 1 T helper cell）相关核心基因，选取4个基因构建分子亚型识别模型。我们发现，1型辅助性T细胞丰度较低与胰腺导管腺癌患者更长的生存期相关。进一步研究显示，基于1型辅助性T细胞特征构建的预后风险评分模型，在预测总生存期与免疫治疗响应方面具有较高准确度。本研究或可加深对1型辅助性T细胞在胰腺导管腺癌患者中作用的理解，并助力这类患者免疫治疗与个性化治疗方案的开发。