Wu Zhixuan, Yang Xuejia, Yuan Ziwei, Guo Yangyang, Wang Xiaowu, Qu Liangchen
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, 318000, China.
Heliyon. 2024 Aug 22;10(17):e36615. doi: 10.1016/j.heliyon.2024.e36615. eCollection 2024 Sep 15.
Gastric cancer (GC) is considered a global health crisis due to the scarcity of early diagnostic methods. Numerous studies have substantiated the involvement of histone acetylation imbalance in the progression of diverse tumor types. The potential roles of long non-coding RNA (lncRNA) in improving prognostic, predictive as well as therapeutic approaches in cancers have made it a major hotspot in recent years. Nevertheless, existent studies have never concerned the prognostic and clinical value of histone acetylation-related lncRNAs (HARlncs) in GC. Based on the aforementioned rationale, we developed a prognostic model incorporating four HARlncs-AC114730.1, AL445250.1, LINC01778, and AL163953.1-which demonstrated potential as an independent predictor of prognosis. Subsequently, GC patients were stratified into high-risk and low-risk groups. The low-risk group exhibited significantly higher overall survival (OS) compared to the high-risk group. Based on the analyses of the tumor microenvironment (TME) and immune responses, significant differences were observed between the two risk groups in terms of immune cell infiltration, immune checkpoint (ICP) expression, and other TME alterations. Furthermore, the sensitivity of GC patients to some chemotherapeutic drugs and the discrepant biological behaviors of three tumor clusters were studied in this model. In summary, we developed an effective HARlncs model with the objective of offering novel prognostic prediction methods and identifying potential therapeutic targets for GC patients.
由于早期诊断方法匮乏，胃癌（GC）被视为全球健康危机。众多研究证实组蛋白乙酰化失衡参与了多种肿瘤类型的进展。长链非编码RNA（lncRNA）在改善癌症的预后、预测及治疗方法方面的潜在作用使其成为近年来的一个主要热点。然而，现有研究从未关注过组蛋白乙酰化相关lncRNAs（HARlncs）在GC中的预后和临床价值。基于上述原理，我们开发了一个包含四个HARlncs（AC114730.1、AL445250.1、LINC01778和AL163953.1）的预后模型，该模型显示出作为独立预后预测指标的潜力。随后，将GC患者分为高风险组和低风险组。与高风险组相比，低风险组的总生存期（OS）显著更长。基于肿瘤微环境（TME）和免疫反应分析，在免疫细胞浸润、免疫检查点（ICP）表达及其他TME改变方面，两个风险组之间存在显著差异。此外，在该模型中研究了GC患者对某些化疗药物的敏感性以及三个肿瘤簇不同的生物学行为。总之，我们开发了一个有效的HARlncs模型，旨在为GC患者提供新的预后预测方法并确定潜在的治疗靶点。
