干扰素-γ (IFN-γ) 是一种关键细胞因子，具有多种生物学功能，包括抗病毒防御、抗肿瘤活性、免疫调节和细胞过程调节。尽管如此，它在胰腺癌（PC）治疗中的作用仍然存在争议。因此，探讨干扰素-γ相关基因（IFN-γGs）在PC发育进程中的作用是值得探讨的。930个PC的转录组数据来源于TCGA、GEO、ICGC和ArrayExpress，其中93个IFN-γGs从 MSigDB 获取。我们研究了泛癌中 IFN-γG 的特性。随后，使用 NMF 算法将 930 名 PC 队列分为两个不同的亚组。然后，我们通过 GSVA 分析检查了这些亚群内癌症相关通路激活的差异。我们仔细检查了这两个亚群中的免疫浸润，并探讨了经典的分子靶药物敏感性变化。最后，我们使用 LASSO 和 Cox 回归分析设计并验证了一种新型 IFN-γ 相关预测模型。此外，我们还进行了 RT-qPCR 和免疫组织化学检测来验证预测模型中包含的 7 个靶基因的表达。我们展示了泛癌中 IFN-γG 的 CNV、SNV、甲基化、表达水平和预后特征。值得注意的是，与簇 1 相比，簇 2 表现出更好的预后结果和更高的免疫细胞浸润。我们还评估了经典分子靶向药物的 IC50 值，以建立 IFN-γG 表达水平和药物反应性之间的联系。此外，通过应用我们的预测模型，我们将 PC 患者分为高风险组和低风险组，确定了顺铂、多西紫杉醇、帕唑帕尼、米斯托林、埃博霉素.B、thapsigargin、bryostatin.1 和 AICAR 对高风险患者的潜在益处PC 患者，以及低风险组患者使用二甲双胍、roscovitine、salubrinal 和环巴明。通过HPA网站数据和PC细胞系和组织中的qRT-PCR检测进一步验证了这些模型基因的表达水平。本研究首次揭示了胰腺癌中IFN-γGs相关的分子亚群，揭示了胰腺癌中IFN-γGs的关键作用。 PC 进展中的 IFN-γG。此外，我们还建立了IFN-γGs相关的预测PC生存的预后模型，为探索IFN-γGs在PC中的精确机制提供了理论基础。版权所有©2023 Chen，Yuan，Guan，Shi，Sun，Wu，Ren 、夏、商。

Interferon-γ (IFN-γ) is a key cytokine with diverse biological functions, including antiviral defense, antitumor activity, immune regulation, and modulation of cellular processes. Nonetheless, its role in pancreatic cancer (PC) therapy remains debated. Therefore, it is worthwhile to explore the role of Interferon-γ related genes (IFN-γGs) in the progression of PC development.Transcriptomic data from 930 PC were sourced from TCGA, GEO, ICGC, and ArrayExpress, and 93 IFN-γGs were obtained from the MSigDB. We researched the characteristics of IFN-γGs in pan-cancer. Subsequently, the cohort of 930 PC was stratified into two distinct subgroups using the NMF algorithm. We then examined disparities in the activation of cancer-associated pathways within these subpopulations through GSVA analysis. We scrutinized immune infiltration in both subsets and probed classical molecular target drug sensitivity variations. Finally, we devised and validated a novel IFN-γ related prediction model using LASSO and Cox regression analyses. Furthermore, we conducted RT-qPCR and immunohistochemistry assays to validate the expression of seven target genes included in the prediction model.We demonstrated the CNV, SNV, methylation, expression levels, and prognostic characteristics of IFN-γGs in pan-cancers. Notably, Cluster 2 demonstrated superior prognostic outcomes and heightened immune cell infiltration compared to Clusters 1. We also assessed the IC50 values of classical molecular targeted drugs to establish links between IFN-γGs expression levels and drug responsiveness. Additionally, by applying our prediction model, we segregated PC patients into high-risk and low-risk groups, identifying potential benefits of cisplatin, docetaxel, pazopanib, midostaurin, epothilone.B, thapsigargin, bryostatin.1, and AICAR for high-risk PC patients, and metformin, roscovitine, salubrinal, and cyclopamine for those in the low-risk group. The expression levels of these model genes were further verified through HPA website data and qRT-PCR assays in PC cell lines and tissues.This study unveils IFN-γGs related molecular subsets in pancreatic cancer for the first time, shedding light on the pivotal role of IFN-γGs in the progression of PC. Furthermore, we establish an IFN-γGs related prognostic model for predicting the survival of PC, offering a theoretical foundation for exploring the precise mechanisms of IFN-γGs in PC.Copyright © 2023 Chen, Yuan, Guan, Shi, Sun, Wu, Ren, Xia and Shang.