Tian Yonggang, Xie Yunqian, Bai Feihu, Wang Jun, Zhang Dekui
Department of Gastroenterology, Lanzhou University Second Hospital, Cuiyingmen No. 82, Chengguan District, Lanzhou, 730030, Gansu Province, China.
The Gastroenterology Clinical Medical Center of Hainan Province, Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Hainan Province, Haikou City, China.
J Gastrointest Cancer. 2024 Jun;55(2):900-912. doi: 10.1007/s12029-024-01028-4. Epub 2024 Mar 1.
Gastric cancer is one of the major public health problems worldwide. Circadian rhythm disturbances driven by circadian clock genes play a role in the development of cancer. However, whether circadian clock genes can serve as potential therapeutic targets and prognostic biomarkers for gastric cancer remains elusive.
In this study, we comprehensively analyzed the potential relationship between circadian clock genes and gastric cancer using online bioinformatics databases such as GEPIA, cBioPortal, STRING, GeneMANIA, Metascape, TIMER, TRRUST, and GEDS.
Biological clock genes are expressed differently in human tumors. Compared with normal tissues, only PER1, CLOCK, and TIMELESS expression differences were statistically significant in gastric cancer (p < 0.05). PER1 (p = 0.0169) and CLOCK (p = 0.0414) were associated with gastric cancer pathological stage (p < 0.05). Gastric cancer patients with high expression of PER1 (p = 0.0028) and NR1D1 (p = 0.016) had longer overall survival, while those with high expression of PER1 (p = 0.042) and NR1D1 (p = 0.016) had longer disease-free survival. The main function of the biological clock gene is related to the circadian rhythms and melatonin metabolism and effects. CLOCK, NPAS2, and KAT2B were key transcription factors for circadian clock genes. In addition, we also found important correlations between circadian clock genes and various immune cells in the gastric cancer microenvironment.
This study may establish a new gastric cancer prognostic indicator based on the biological clock gene and develop new drugs for the treatment of gastric cancer using biological clock gene targets.
胃癌是全球主要的公共卫生问题之一。由生物钟基因驱动的昼夜节律紊乱在癌症发展中起作用。然而，生物钟基因是否可作为胃癌的潜在治疗靶点和预后生物标志物仍不清楚。
在本研究中，我们使用GEPIA、cBioPortal、STRING、GeneMANIA、Metascape、TIMER、TRRUST和GEDS等在线生物信息学数据库全面分析了生物钟基因与胃癌之间的潜在关系。
生物钟基因在人类肿瘤中的表达存在差异。与正常组织相比，仅PER1、CLOCK和TIMELESS在胃癌中的表达差异具有统计学意义（p < 0.05）。PER1（p = 0.0169）和CLOCK（p = 0.0414）与胃癌病理分期相关（p < 0.05）。PER1（p = 0.0028）和NR1D1（p = 0.016）高表达的胃癌患者总生存期较长，而PER1（p = 0.042）和NR1D1（p = 0.016）高表达的患者无病生存期较长。生物钟基因的主要功能与昼夜节律、褪黑素代谢及作用有关。CLOCK、NPAS2和KAT2B是生物钟基因的关键转录因子。此外，我们还发现生物钟基因与胃癌微环境中的各种免疫细胞之间存在重要相关性。
本研究可能基于生物钟基因建立新的胃癌预后指标，并利用生物钟基因靶点开发治疗胃癌的新药。
