Pancreatic cancer (PC) is a highly metastatic malignant tumor of the digestive system. Drug resistance frequently occurs during cancer treatment process. This study aimed to explore the link between chemoresistance and tumor metastasis in PC and its possible molecular and cellular mechanisms. A Metastasis and Chemoresistance Signature (MCS) scoring system was built and validated based on metastasis- and chemoresistance-related genes using gene expression data of PC, and the model was applied to single-cell RNA sequencing data. The influence of linker histone H1.2 (H1–2) on PC was explored through in vitro and in vivo experiments including proliferation, invasion, migration, drug sensitivity, rescue experiments and immunohistochemistry, emphasizing its regulation with c-MYC signaling pathway. A novel MCS scoring system accurately predicted PC patient survival and was linked to chemoresistance and epithelial-mesenchymal transition (EMT) in PC single-cell RNA sequencing data. H1–2 emerged as a significant prognostic factor, with its high expression indicating increased chemoresistance and EMT. This upregulation was mediated by c-MYC, which was also found to be highly expressed in PC tissues. The MCS scoring system offers insights into PC chemoresistance and metastasis potential. Targeting H1–2 could enhance therapeutic strategies and improve PC patient outcomes.

中文翻译：

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组蛋白H1.2在胰腺癌转移和化疗耐药中的作用

胰腺癌（PC）是一种高度转移的消化系统恶性肿瘤。癌症治疗过程中经常出现耐药现象。本研究旨在探讨PC化疗耐药与肿瘤转移之间的联系及其可能的分子和细胞机制。利用PC的基因表达数据，基于转移和化疗耐药相关基因构建并验证了转移和化疗耐药特征（MCS）评分系统，并将该模型应用于单细胞RNA测序数据。通过增殖、侵袭、迁移、药物敏感性、拯救实验和免疫组化等体外和体内实验探讨连接组蛋白H1.2（H1-2）对PC的影响，强调其通过c-MYC信号通路的调节。一种新型 MCS 评分系统准确预测 PC 患者的生存率，并与 PC 单细胞 RNA 测序数据中的化疗耐药性和上皮间质转化 (EMT) 相关。H1-2 成为一个重要的预后因素，其高表达表明化疗耐药性和 EMT 增加。这种上调是由 c-MYC 介导的，c-MYC 也被发现在 PC 组织中高表达。MCS 评分系统可深入了解 PC 化疗耐药性和转移潜力。针对 H1-2 可以增强治疗策略并改善 PC 患者的预后。