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肝癌患者中CLOCK、BMAL1、CRY1、CRY2、PER1、PER2、PER3和NPAS2蛋白基因变化的生物信息学分析

Bioinformatic analysis of genetic changes CLOCK, BMAL1, CRY1, CRY2, PER1, PER2, PER3, and NPAS2 proteins in HCC patients.

作者信息

Ayan Durmus, Cagatay Ak

机构信息

Department of Medical Biochemistry, Nigde Training and Research Hospital, Nigde, Turkiye.

Department of Medical Biochemistry, Nigde Omer Halisdemir University, School of Medicine, Nigde, Turkiye.

出版信息

Hepatol Forum. 2023 Sep 20;4(3):108-117. doi: 10.14744/hf.2023.2023.0009. eCollection 2023.

DOI:10.14744/hf.2023.2023.0009
PMID:37822309
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10564247/
Abstract

BACKGROUND AND AIM

Genes related to the circadian rhythm control various biological processes. The aim of this study was to comprehensively investigate the mutational and mRNA profile of core circadian rhythm genes in hepatocellular cancer (HCC) samples.

MATERIALS AND METHODS

In this study, the gene profile of a total of 369 patients with HCC was examined over the data obtained from the cancer genome atlas database through-cBioPortal. The effects of mutations on protein were examined by scoring the Polymorphism Phenotyping v2, Mutation Assessor, and SIFT-databases. While the association of genes with other genes was determined with the GeneMANIA-database, the association of expression levels in the genes with overall survival (OS) was evaluated with the Kaplan-Meier Plot database.

RESULTS

As a result of the analyses, there were a total of 25 mutations. Decreased expression levels of PER1 (1.3e-05), PER3 (p=0.046), and CRY2 (p=1.8e-06) genes were found statistically associated with shorter OS. It was also found that increased expression levels of the PER2 (p=0.045) gene were associated with longer OS, and increased expression levels of the NPAS2 (p=9e-04) gene were associated with shorter OS.

CONCLUSION

In particular, changes in the PER1, PER2, CRY2, and NPAS2 genes may provide possible molecular targets in chemotherapy and immunotherapy for HCC patients.

摘要

背景与目的

与昼夜节律相关的基因控制着各种生物过程。本研究的目的是全面调查肝细胞癌（HCC）样本中核心昼夜节律基因的突变情况和mRNA谱。

材料与方法

在本研究中，通过cBioPortal从癌症基因组图谱数据库获取的数据，检查了总共369例HCC患者的基因谱。通过对多态性表型分析v2、突变评估器和SIFT数据库进行评分，研究突变对蛋白质的影响。使用GeneMANIA数据库确定基因与其他基因的关联，使用Kaplan-Meier Plot数据库评估基因表达水平与总生存期（OS）的关联。

结果

分析结果显示，共有25个突变。发现PER1（1.3e-05）、PER3（p=0.046）和CRY2（p=1.8e-06）基因的表达水平降低与较短的OS在统计学上相关。还发现PER2（p=0.045）基因表达水平升高与较长的OS相关，NPAS2（p=9e-04）基因表达水平升高与较短的OS相关。

结论

特别是，PER1、PER2、CRY2和NPAS2基因的变化可能为HCC患者的化疗和免疫治疗提供可能的分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/0bf399b30e60/hf-4-108-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/fbd99d496eb1/hf-4-108-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/1e8b11bda394/hf-4-108-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/e9c2479e6d5d/hf-4-108-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/434cb45374e8/hf-4-108-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/4faf2213191c/hf-4-108-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/0bf399b30e60/hf-4-108-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/fbd99d496eb1/hf-4-108-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/7e3457d27042/hf-4-108-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/1e8b11bda394/hf-4-108-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/e9c2479e6d5d/hf-4-108-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/434cb45374e8/hf-4-108-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/4faf2213191c/hf-4-108-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfb/10564247/0bf399b30e60/hf-4-108-g007.jpg

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4
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