Xu Zi-Jin, Li Peng-Cheng, Wang Wen-Quan, Liu Liang
Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Surgery Training Base, Fudan University Shanghai Cancer Center Shanghai, China.
J Gastrointest Oncol. 2022 Dec;13(6):3193-3206. doi: 10.21037/jgo-22-333.
Pancreatic adenocarcinoma, the deadliest malignant cancer, has gradually become the third leading cause of cancer-related death. Multidisciplinary therapy has been difficult to implement because of the particularity of pancreatic adenocarcinoma. Research has increasingly indicated the significance of metabolic adaption in pancreatic adenocarcinoma. The difference in metabolism may influence immune cell infiltration in pancreatic adenocarcinoma. Novel immune-related metabolism biomarkers are needed to improve the therapeutic outcomes of existing targeted therapies.
We enrolled whole-genome sequencing data and clinical information about 168 pancreatic adenocarcinoma samples from The Cancer Genome Atlas (TCGA) database, other pancreatic adenocarcinoma samples, and clinical information from other cohorts. We used the gene set variation analysis (GSVA) package to calculate feature score, the weighted gene co-expression network analysis (WGCNA) and randomSurvivalForest package to screen hub genes, the ConsenClusterPlus package to classify subtypes, the pRRopthetic package to evaluate drug sensibility, the maftools package to analyze mutation information and the Seurat package to analyze single cell sequencing data.
We revealed the prognosis significance of Th2 cell infiltration, classified two subtypes based on hub genes, compared immune cell infiltration, substance metabolism, cellular processes, gene mutation, and copy number variation (CNV) between subtypes and explored the clinical and biological features of Th2 cell infiltration.
We displayed the poor prognosis significance of Th2 cell infiltration and the significant difference of simple nucleotide polymorphism, CNV, natural killer (NK) CD56 bright cell infiltration, substance metabolism, autophagy and necroptosis between subtypes. Additionally, we discovered the sensitivity difference of chemotherapy drug and the Th2 cell infiltration changes after chimeric antigen receptor T cells (CAR-T) cell therapy and radiotherapy and explored the differences between normal liver and metastatic liver tissues of pancreatic adenocarcinoma patients.
胰腺腺癌是最致命的恶性肿瘤，已逐渐成为癌症相关死亡的第三大主要原因。由于胰腺腺癌的特殊性，多学科治疗难以实施。研究越来越表明代谢适应在胰腺腺癌中的重要性。代谢差异可能影响胰腺腺癌中的免疫细胞浸润。需要新的免疫相关代谢生物标志物来改善现有靶向治疗的疗效。
我们收集了来自癌症基因组图谱（TCGA）数据库的168例胰腺腺癌样本的全基因组测序数据和临床信息、其他胰腺腺癌样本以及其他队列的临床信息。我们使用基因集变异分析（GSVA）软件包计算特征分数，使用加权基因共表达网络分析（WGCNA）和randomSurvivalForest软件包筛选枢纽基因，使用ConsenClusterPlus软件包进行亚型分类，使用pRRopthetic软件包评估药物敏感性，使用maftools软件包分析突变信息，使用Seurat软件包分析单细胞测序数据。
我们揭示了Th2细胞浸润的预后意义，基于枢纽基因分类出两种亚型，比较了亚型之间的免疫细胞浸润、物质代谢、细胞过程、基因突变和拷贝数变异（CNV），并探讨了Th2细胞浸润的临床和生物学特征。
我们展示了Th2细胞浸润的预后不良意义以及亚型之间单核苷酸多态性、CNV、自然杀伤（NK）CD56亮细胞浸润、物质代谢、自噬和坏死性凋亡的显著差异。此外，我们发现了化疗药物的敏感性差异以及嵌合抗原受体T细胞（CAR-T）细胞治疗和放疗后Th2细胞浸润的变化，并探讨了胰腺腺癌患者正常肝脏组织和转移肝脏组织之间的差异。
