Biological Clock Genes are Crucial and Promising Biomarkers for the Therapeutic Targets and Prognostic Assessment in Gastric Cancer.

Bioinformatics Biological clock genes Gastric adenocarcinoma Genetic alterations Signaling pathways Tumor microenvironment

Journal

Journal of gastrointestinal cancer
ISSN: 1941-6636
Titre abrégé: J Gastrointest Cancer
Pays: United States
ID NLM: 101479627

Informations de publication

Date de publication:
01 Mar 2024
Historique:
accepted: 05 02 2024
medline: 1 3 2024
pubmed: 1 3 2024
entrez: 1 3 2024
Statut: aheadofprint

Résumé

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.

Sections du résumé

BACKGROUND BACKGROUND
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.
METHODS METHODS
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.
RESULTS RESULTS
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.
CONCLUSIONS CONCLUSIONS
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.

Identifiants

DOI: 10.1007/s12029-024-01028-4 PMID: 38427147
pubmed: 38427147
doi: 10.1007/s12029-024-01028-4
pii: 10.1007/s12029-024-01028-4
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Hainan Province Clinical Medical Center
ID : 2021818
Organisme : the specific research fund of The Innovation Platform for Academicians of Hainan Province
ID : 2022136
Organisme : Hainan Provincial Health Industry Research Project
ID : 22A200078
Organisme : Medical Innovation and Development Project of Lanzhou University
ID : lzuyxcx-2022-181

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Yonggang Tian (Y)

Department of Gastroenterology, Lanzhou University Second Hospital, Cuiyingmen No. 82, Chengguan District, Lanzhou, 730030, Gansu Province, China.

Yunqian Xie (Y)

The Gastroenterology Clinical Medical Center of Hainan Province, Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Hainan Province, Haikou City, China.

Feihu Bai (F)

The Gastroenterology Clinical Medical Center of Hainan Province, Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Hainan Province, Haikou City, China. baifeihu@sohu.com.

Jun Wang (J)

Department of Gastroenterology, 986 Hospital, Xijing Hospital, Air Force Military Medical University, No. 269, Youyi East Road, Xi'an, Shaanxi Province, 710089, China. wangjundoctor@aliyun.com.

Dekui Zhang (D)

Department of Gastroenterology, Lanzhou University Second Hospital, Cuiyingmen No. 82, Chengguan District, Lanzhou, 730030, Gansu Province, China. zhangdk8616@126.com.

Classifications MeSH