张昱 任瑞平 万鹏 贺晓兰

摘要：目的 构建整合胰腺导管腺癌（PDAC）分子亚型和免疫相关基因的风险评估模型。方法 以GSE71729数据集（n=145）为训练集，整合PDAC鳞状和非鳞状亚型之间差异表达基因和差异免疫相关基因构建调控网络，筛选发挥主调控鳞状亚型的5个免疫标志基因。基于患者生存信息和免疫标志基因构建整合免疫评分（IIS）模型来预测PDAC患者的临床预后，并在5个验证集（n=758）中检验其预测效能。结果 根据IIS将PDAC患者分为高危组和低危组。在训练集和验证集中，高危组患者的总体生存期均短于低危组（P均<0.001）。多变量Cox回归分析显示IIS是PDAC的独立预后因子（HR=2.16，95%CI=1.50～3.10，P<0.001）。结论 IIS可用于PDAC患者的危险分层，并可能成为PDAC潜在的预后标志物。

关键词：胰腺导管腺癌；免疫相关基因；预后

中图分类号： R735.9  文献标识码： A  文章编号：1000-503X（2024）03-0354-07

DOI：10.3881/j.issn.1000-503X.15736

Construction and Evaluation of a Prognostic Risk Prediction Model of Pancreatic Ductal Adenocarcinoma Based on Immune-Related Genes

ZHANG Yu，REN Ruiping，WAN Peng，HE Xiaolan

Cancer Radiotherapy and Chemotherapy Center，The Affiliated Peoples Hospital of Ningbo University，Ningbo，Zhejiang 315040，China

Corresponding author：ZHANG Yu Tel：0574-87017563，E-mail：zy95589034@163.com

ABSTRACT：Objective To construct a risk prediction model by integrating the molecular subtypes of pancreatic ductal adenocarcinoma （PDAC） and immune-related genes.Methods With GSE71729 data set （n=145） as the training set，the differentially expressed genes and differential immune-related genes between the squamous and non-squamous subtypes of PDAC were integrated to construct a regulatory network，on the basis of which five immune marker genes regulating the squamous subtype were screened out.An integrated immune score （IIS） model was constructed based on patient survival information and immune marker genes to predict the clinical prognosis of PDAC patients，and its predictive performance was tested with 5 validation sets （n=758）.Results PDAC patients were assigned into high risk and low risk groups according to the IIS.In both training and validation sets，the overall survival of patients in the high risk group was shorter than that in the low risk group （both P<0.001）.The multivariable Cox regression showed that IIS was an independent prognostic factor for PDAC （HR=2.16，95%CI=1.50-3.10，P<0.001）.Conclusion IIS can be used for risk stratification of PDAC patients and may become a potential prognostic marker for PDAC.

Key words：pancreatic ductal adenocarcinoma；immune-related gene；prognosis

Acta Acad Med Sin，2024，46（3）：354-360

胰腺导管腺癌（pancreatic ductal adenocarcinoma，PDAC）是一种常见的消化道恶性肿瘤，占胰腺癌组织学类型的90%以上，是全球第七大癌症相关死亡原因［1］，在我国其患病人数呈逐年上升趋势［2］。尽管近些年PDAC的治疗策略有所改进，但其预后情况仍然十分严峻，5年存活率仅为9%［3］。由于患者个体差异及疾病的异质性，手术和化疗的治疗效果存在差异［4-5］。对PDAC患者进行危险分层，有助于制订精准和个体化的治疗方案，改善患者预后和临床转归。高通量测序技术的不断进步，为揭示基因表达和修饰特性提供了有力支持，从而能够更有效地开发与PDAC预后评估紧密相关的生物标志物［6-8］。根据表达谱聚类结果，PDAC可分为鳞状亚型、胰腺祖细胞亚型、免疫原性亚型和内/外分泌腺异常分化亚型，其中鳞状亚型约占31%，侵袭转移能力强，预后相对较差，中位生存期仅为13.3个月［9］。……