Functional polymorphisms in circadian positive feedback loop genes predict postsurgical prognosis of gastric cancer
Abstract Background Circadian positive feedback loop (CPFL) genes (CLOCK, BAML1, and NPAS2) have been implicated in cancer initiation and progression. The purpose of this study was to explore the effects of single‐nucleotide polymorphisms (SNPs) in CPFL genes on prognosis of gastric cancer (GC) pati...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-04-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.2050 |
| _version_ | 1797387180776095744 |
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| author | Yibing Chen Dandan Wang Yucen Song Xiaofei Zhang Zhihui Jiao Juqin Dong Lin Lü Zhengzhi Zou Wei Du Falin Qu |
| author_facet | Yibing Chen Dandan Wang Yucen Song Xiaofei Zhang Zhihui Jiao Juqin Dong Lin Lü Zhengzhi Zou Wei Du Falin Qu |
| author_sort | Yibing Chen |
| collection | DOAJ |
| description | Abstract Background Circadian positive feedback loop (CPFL) genes (CLOCK, BAML1, and NPAS2) have been implicated in cancer initiation and progression. The purpose of this study was to explore the effects of single‐nucleotide polymorphisms (SNPs) in CPFL genes on prognosis of gastric cancer (GC) patients. Methods Nine functional SNPs from the three CPFL genes were genotyped in a cohort of 704 GC patients undergoing resection. Multivariate Cox regression model and Kaplan‐Meier curve were used for prognosis analysis. Results Among the nine SNPs, rs11133399 in CLOCK, rs1044432 and rs2279284 in BAML1 were significantly associated with GC overall survival and recurrence‐free survival. The unfavorable genotypes of these SNPs showed a cumulative effect on GC prognosis. Multivariate assessment model indicated that these SNPs, in conjunction with clinical variables, enhanced the power to predict GC prognosis. In addition, survival tree analysis revealed the genotype of rs11133399 as a primary risk factor contributing to the prognosis of GC patients. Functional assays showed that the G allele in rs11133399 significantly enhanced luciferase reporter activity than A allele. Immunohistochemical analysis further demonstrated that the genotype of rs11133399 was significantly associated with the expression level of CLOCK in GC tissues, suggesting that this SNP might affect the prognosis of GC through its influence on the expression of CLOCK gene. Conclusions Our data indicate that SNPs in CPFL genes might contribute to the clinical outcome of GC through their impact on gene expression. Further studies are needed to elucidate its underlying molecular mechanisms. |
| first_indexed | 2024-03-08T22:20:09Z |
| format | Article |
| id | doaj.art-48e66731659d46d8bdd0fab30ee9e142 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-08T22:20:09Z |
| publishDate | 2019-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-48e66731659d46d8bdd0fab30ee9e1422023-12-18T12:55:50ZengWileyCancer Medicine2045-76342019-04-01841919192910.1002/cam4.2050Functional polymorphisms in circadian positive feedback loop genes predict postsurgical prognosis of gastric cancerYibing Chen0Dandan Wang1Yucen Song2Xiaofei Zhang3Zhihui Jiao4Juqin Dong5Lin Lü6Zhengzhi Zou7Wei Du8Falin Qu9Genetic and Prenatal Diagnosis Center First Affiliated Hospital Zhengzhou University Zhengzhou ChinaShandong Medicinal Biotechnology Centre, Key Laboratory for Rare & Uncommon Diseases of Shandong Province Back and Neck Pain Hospital, Shandong Academy of Medical Sciences Jinan ChinaGenetic and Prenatal Diagnosis Center First Affiliated Hospital Zhengzhou University Zhengzhou ChinaDepartment of Medical Oncology First Affiliated Hospital Zhengzhou University Zhengzhou ChinaGenetic and Prenatal Diagnosis Center First Affiliated Hospital Zhengzhou University Zhengzhou ChinaCell‐Gene Therapy Translational Medicine Research Center The Third Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Medical Oncology Guangzhou First People's Hospital Guangzhou Medical University Guangzhou ChinaMOE Key Laboratory of Laser Life Science and Institute of Laser Life Science College of Biophotonics South China Normal University Guangzhou ChinaDepartment of Neurosurgery First Affiliated Hospital Zhengzhou University Zhengzhou ChinaDepartment of General Surgery Tangdu Hospital Fourth Military Medical University Xi'an ChinaAbstract Background Circadian positive feedback loop (CPFL) genes (CLOCK, BAML1, and NPAS2) have been implicated in cancer initiation and progression. The purpose of this study was to explore the effects of single‐nucleotide polymorphisms (SNPs) in CPFL genes on prognosis of gastric cancer (GC) patients. Methods Nine functional SNPs from the three CPFL genes were genotyped in a cohort of 704 GC patients undergoing resection. Multivariate Cox regression model and Kaplan‐Meier curve were used for prognosis analysis. Results Among the nine SNPs, rs11133399 in CLOCK, rs1044432 and rs2279284 in BAML1 were significantly associated with GC overall survival and recurrence‐free survival. The unfavorable genotypes of these SNPs showed a cumulative effect on GC prognosis. Multivariate assessment model indicated that these SNPs, in conjunction with clinical variables, enhanced the power to predict GC prognosis. In addition, survival tree analysis revealed the genotype of rs11133399 as a primary risk factor contributing to the prognosis of GC patients. Functional assays showed that the G allele in rs11133399 significantly enhanced luciferase reporter activity than A allele. Immunohistochemical analysis further demonstrated that the genotype of rs11133399 was significantly associated with the expression level of CLOCK in GC tissues, suggesting that this SNP might affect the prognosis of GC through its influence on the expression of CLOCK gene. Conclusions Our data indicate that SNPs in CPFL genes might contribute to the clinical outcome of GC through their impact on gene expression. Further studies are needed to elucidate its underlying molecular mechanisms.https://doi.org/10.1002/cam4.2050circadian genegastric cancerprognosissingle‐nucleotide polymorphism |
| spellingShingle | Yibing Chen Dandan Wang Yucen Song Xiaofei Zhang Zhihui Jiao Juqin Dong Lin Lü Zhengzhi Zou Wei Du Falin Qu Functional polymorphisms in circadian positive feedback loop genes predict postsurgical prognosis of gastric cancer Cancer Medicine circadian gene gastric cancer prognosis single‐nucleotide polymorphism |
| title | Functional polymorphisms in circadian positive feedback loop genes predict postsurgical prognosis of gastric cancer |
| title_full | Functional polymorphisms in circadian positive feedback loop genes predict postsurgical prognosis of gastric cancer |
| title_fullStr | Functional polymorphisms in circadian positive feedback loop genes predict postsurgical prognosis of gastric cancer |
| title_full_unstemmed | Functional polymorphisms in circadian positive feedback loop genes predict postsurgical prognosis of gastric cancer |
| title_short | Functional polymorphisms in circadian positive feedback loop genes predict postsurgical prognosis of gastric cancer |
| title_sort | functional polymorphisms in circadian positive feedback loop genes predict postsurgical prognosis of gastric cancer |
| topic | circadian gene gastric cancer prognosis single‐nucleotide polymorphism |
| url | https://doi.org/10.1002/cam4.2050 |
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