Department of Surgery, Suzhou Hospital of Anhui Medical University, Suzhou, PR China.
Department of Gastroenterology, Suzhou Hospital of Anhui Medical University, Suzhou, PR China.
Clinics (Sao Paulo). 2024 Aug 28;79:100481. doi: 10.1016/j.clinsp.2024.100481. eCollection 2024.
To comprehensively analyze the clinical significance of Immune Checkpoint-Related Genes (ICRGs) in Pancreatic Adenocarcinoma (PAAD).
PAAD tissues and normal pancreatic tissues were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, and 283 ICRGs were integrated by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome datasets. Unsupervised clustering was used to obtain potential ICRGs-based PAAD subtypes. Wilcoxon test was performed to screen Differentially Expressed ICRGs (DEICRGs), while cox regression analyses were utilized to identify prognosis-related ICRGs and clinicopathological factors, and construct the corresponding models. The Tumor Immune Microenvironment (TIME) was evaluated. Moreover, the authors performed enrichment analysis, Gene Set Enrichment Analysis (GSEA), and transcription factor regulatory networks to realize underlying mechanisms.
Three ICRGs-based PAAD subtypes were identified, and they were associated with three ESTIMATE scores, a Tumor Microenvironment (TMB) score, 14 therapeutic immune checkpoints, and infiltration levels of seven immune cells. On top of that, the authors constructed two signatures based on DEICRGs to predict the Overall Survival (OS) (Area Under the ROC Curve [AUC: 0.741∼0.778]) and Progression-Free Survival (PFS) (AUC: 0.746∼0.831) of patients. Two nomograms were established by combining clinical variables and signatures. In addition, the authors found higher infiltration of naïve B cells and CD8 T-cells in low-risk PAAD patients, and higher infiltration of suppressive immune cells and cancer-related signaling pathways in high-risk PAAD patients.
The present study suggested that ICRGs were associated with TIME formation and prognosis of PAAD patients, which may serve as novel clinical biomarkers and therapeutic targets.
全面分析免疫检查点相关基因（ICRGs）在胰腺导管腺癌（PAAD）中的临床意义。
从癌症基因组图谱（TCGA）和基因型组织表达（GTEx）数据库中获取 PAAD 组织和正常胰腺组织，通过京都基因与基因组百科全书（KEGG）和反应组数据集整合 283 个 ICRGs。采用无监督聚类获得潜在的基于 ICRGs 的 PAAD 亚型。采用 Wilcoxon 检验筛选差异表达的 ICRGs（DEICRGs），同时采用 cox 回归分析识别与预后相关的 ICRGs 和临床病理因素，并构建相应的模型。评估肿瘤免疫微环境（TIME）。此外，作者还进行了富集分析、基因集富集分析（GSEA）和转录因子调控网络分析，以实现潜在机制。
鉴定出三种基于 ICRGs 的 PAAD 亚型，它们与三个 ESTIMATE 评分、肿瘤微环境（TMB）评分、14 个治疗性免疫检查点以及七种免疫细胞的浸润水平相关。此外，作者构建了两个基于 DEICRGs 的signature，以预测患者的总生存期（OS）（AUC：0.741∼0.778）和无进展生存期（PFS）（AUC：0.746∼0.831）。通过结合临床变量和 signature 建立了两个 nomogram。此外，作者发现低风险 PAAD 患者中幼稚 B 细胞和 CD8 T 细胞的浸润较高，而高风险 PAAD 患者中抑制性免疫细胞和癌症相关信号通路的浸润较高。
本研究表明，ICRGs 与 PAAD 患者的 TIME 形成和预后相关，可能成为新的临床生物标志物和治疗靶点。
