Wang Qingqing, Zhou Shuning, Hu Xinyi, Wang Xianggang, Wu Xue, Huai Ziyou, Gao Yu, Li Shujing
School of Life Science, Bengbu Medical College, Bengbu 233030, China.
Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu 233030, China.
Life (Basel). 2023 Apr 30;13(5):1116. doi: 10.3390/life13051116.
Pancreatic cancer (PACA) is a highly malignant tumor with a poor prognosis. Recent studies have discovered substantial differences in the expression levels of several circadian genes in PACA samples compared to normal samples. The goal of this research was to find differentially expressed rhythm genes (DERGs) in PACA samples and determine their role in the development of PACA. A total of 299 DERGs were identified in PACA, including 134 downregulated genes and 165 upregulated genes. DERGs were significantly abundant in the metabolic pathway and immune response pathways, according to GO and KEGG analyses. Survival analyses showed that PACA patients who had higher expression levels of MBOAT2/CDA/LPCAT2/B4GALT5 had shorter overall survival times. Using cell assay verification, the mRNA levels of MBOAT2/CDA/LPCAT2/B4GALT5 in Patu-8988 and PNAC-1 cells were found to be significantly higher than those in HPDE6-C7 cells, which was in line with previous studies on PACA patient data. Through conducting univariate Cox analysis, it was determined that MBOAT2/CDA/LPCAT2/B4GALT5 expression, age and grade were all high-risk factors. The MBOAT2/CDA/LPCAT2/B4GALT5 genes were independently correlated with overall survival, according to the multivariate Cox analysis. The proportion of immune cells in PACA and normal samples significantly changed, according to the immune infiltration analysis. Furthermore, MBOAT2/CDA/LPCAT2/B4GALT5 expression levels were significantly related to the level of immune cell infiltration. The protein-protein interaction network of the MBOAT2/CDA/LPCAT2/B4GALT5 genes included 54 biological nodes and 368 interacting genes. In conclusion, the finding of these DERGs adds to the investigation of the molecular processes underlying the onset and progression of PACA. In the future, DERGs may serve as prognostic and diagnostic biomarkers as well as drug targets for chronotherapy in PACA patients.
胰腺癌（PACA）是一种预后较差的高度恶性肿瘤。最近的研究发现，与正常样本相比，PACA样本中几种昼夜节律基因的表达水平存在显著差异。本研究的目的是在PACA样本中寻找差异表达的节律基因（DERGs），并确定它们在PACA发生发展中的作用。在PACA中总共鉴定出299个DERGs，其中包括134个下调基因和165个上调基因。根据基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，DERGs在代谢途径和免疫反应途径中显著富集。生存分析表明，MBOAT2/CDA/LPCAT2/B4GALT5表达水平较高的PACA患者总生存时间较短。通过细胞试验验证，发现Patu-8988和PNAC-1细胞中MBOAT2/CDA/LPCAT2/B4GALT5的mRNA水平显著高于HPDE6-C7细胞，这与之前对PACA患者数据的研究一致。通过进行单变量Cox分析，确定MBOAT2/CDA/LPCAT2/B4GALT5表达、年龄和分级均为高危因素。根据多变量Cox分析，MBOAT2/CDA/LPCAT2/B4GALT5基因与总生存独立相关。根据免疫浸润分析，PACA和正常样本中免疫细胞的比例发生了显著变化。此外，MBOAT2/CDA/LPCAT2/B4GALT5表达水平与免疫细胞浸润水平显著相关。MBOAT2/CDA/LPCAT2/B4GALT5基因的蛋白质-蛋白质相互作用网络包括54个生物学节点和368个相互作用基因。总之，这些DERGs的发现为PACA发病和进展的分子机制研究增添了内容。未来，DERGs可能作为PACA患者的预后和诊断生物标志物以及时辰疗法的药物靶点。
