Department of Frontier Health Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan.
Faculty of Physical Education, Qu Jing Normal University, Yun Nan, P.R. China.
Anticancer Res. 2024 Oct;44(10):4233-4250. doi: 10.21873/anticanres.17254.
BACKGROUND/AIM: Pancreatic cancer is the fourth leading cause of cancer-related death in both men and women worldwide. The 5-year relative survival rate for pancreatic ductal adenocarcinoma (PDAC) is 10%, which is the lowest among all cancers. This study aimed to find more effective targets to improve the diagnosis, prognostic prediction, and treatment of PDAC.
Three datasets were selected from the GEO database. Correlation analysis was used to screen the datasets and samples. Differentially expressed genes were identified using GEO2R. Metascape was used to perform pathway and process enrichment analysis. Survival analysis using the GEPIA2 and Kaplan-Meier plotter databases was conducted to filter hub genes. Principal component analysis and LASSO regression analyses were used to further filter the key genes. Gene expression in PDAC and normal tissues and in different pathological stages was analyzed using the GEPIA2 database. Thereafter, gene expression was detected in three PDAC and HPDE cell lines using real-time polymerase chain reaction.
LPAR5, CYP2C18, SERPINH1, ACSL5, and HCAR3 exhibited higher transcription levels in PDAC tissues compared to matched normal tissues, whereas the PNLIP expression was lower. LPAR5, CYP2C18, SERPINH1 and ACSL5 were markedly upregulated in stage IV PDAC. LPAR5, CYP2C18, SERPINH1 and ACSL5 were upregulated in PDAC cell lines. Further verification suggested that the expression levels of these four genes were closely related to histological type, pathologic stage, therapeutic effects and prognosis of pancreatic cancer.
LPAR5, CYP2C18, SERPINH1 and ACSL5 may serve as potential diagnostic, prognostic, and therapeutic targets for PDAC.
背景/目的：胰腺癌是全球男性和女性癌症相关死亡的第四大主要原因。胰腺导管腺癌 (PDAC) 的 5 年相对生存率为 10%，是所有癌症中最低的。本研究旨在寻找更有效的靶点，以改善 PDAC 的诊断、预后预测和治疗。
从 GEO 数据库中选择了三个数据集。使用相关性分析筛选数据集和样本。使用 GEO2R 鉴定差异表达基因。使用 Metascape 进行通路和过程富集分析。使用 GEPIA2 和 Kaplan-Meier plotter 数据库进行生存分析，以筛选枢纽基因。使用主成分分析和 LASSO 回归分析进一步筛选关键基因。使用 GEPIA2 数据库分析 PDAC 和正常组织以及不同病理阶段的基因表达。然后，使用实时聚合酶链反应检测三种 PDAC 和 HPDE 细胞系中的基因表达。
与匹配的正常组织相比，LPAR5、CYP2C18、SERPINH1、ACSL5 和 HCAR3 在 PDAC 组织中表现出更高的转录水平，而 PNLIP 的表达水平较低。LPAR5、CYP2C18、SERPINH1 和 ACSL5 在 IV 期 PDAC 中显著上调。LPAR5、CYP2C18、SERPINH1 和 ACSL5 在 PDAC 细胞系中上调。进一步验证表明，这四个基因的表达水平与胰腺癌的组织学类型、病理分期、治疗效果和预后密切相关。
LPAR5、CYP2C18、SERPINH1 和 ACSL5 可能成为 PDAC 的潜在诊断、预后和治疗靶点。
