Circadian rhythm related genes signature in glioma for drug resistance prediction: a comprehensive analysis integrating transcriptomics and machine learning

被引：0

作者：

Liao, Junbo ^{[1
,2
,3
]}

Duan, Yingxing ^{[4
]}

Xu, Xiangwang ^{[1
,2
,3
]}

Liu, Yaxue ^{[1
,2
,3
]}

Zhan, Chaohong ^{[1
,2
,3
]}

Xiao, Gelei ^{[1
,2
,3
]}

机构：

[1] Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Peoples R China

[2] Cent South Univ, Xiangya Hosp, Diag & Treatment Ctr Hydrocephalus, Changsha, Peoples R China

[3] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China

[4] Cent South Univ, XiangYa Hosp, Dept Radiol, Changsha 410008, Hunan, Peoples R China

来源：

DISCOVER ONCOLOGY | 2025年 / 16卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Glioma; Circadian rhythm; Chemotherapy; Drug resistance; Innate immune; MICROGLIA; INSOMNIA; TUMORS;

D O I：

10.1007/s12672-025-01863-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundGliomas, 24% of all primary brain tumors, have diverse histology and poor survival rates, with about 70% recurring due to acquired or de novo resistance. Insomnia in patients is correlated strongly with circadian rhythm disruptions. The correlation between circadian rhythm disorders and drug resistance of some tumors has been proved. However, the precise mechanism underlying the relationship between glioma and circadian rhythm disorders has not been elucidated.MethodsCircadian rhythm-related genes (CRRGs) were identified using the least absolute shrinkage and selection operator (LASSO) regression, and stochastic gradient descent (SGD) was performed to form a circadian rhythm-related score (CRRS) model. The studies of immune cell infiltration, genetic variations, differential gene expression pattern, and single cell analysis were performed for exploring the mechanisms of chemotherapy resistance in glioma. The relationship between CRRGs and chemosensitivity was also confirmed by IC 50 (half maximal inhibitory concentration) analysis.ResultSignatures of 16 CRRGs were screened out and identified. Based on the CRRS model, an optimal comprehensive nomogram was created, exhibiting a favorable potential for predicting drug resistance in samples. Immune infiltration, cell-cell communication, and single cell analysis all indicated that high CRRS group was closely related to innate immune cells. IC50 analysis showed that CRRG knockdown enhanced the chemosensitivity of glioma.ConclusionA significant correlation between CRRGs, drug resistance of glioma, and innate immune cells was found, which might hold a significant role in the drug resistance of glioma.

引用

页数：23

共 91 条

[11] Timing gone awry: distinct tumour suppressive and oncogenic roles of the circadian clock and crosstalk with hypoxia signalling in diverse malignancies [J].

Chang, Wai Hoong ;

Lai, Alvina G. .

JOURNAL OF TRANSLATIONAL MEDICINE, 2019, 17

[12] Clock Genes and Altered Sleep-Wake Rhythms: Their Role in the Development of Psychiatric Disorders [J].

Charrier, Annaelle ;

Olliac, Bertrand ;

Roubertoux, Pierre ;

Tordjman, Sylvie .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (05)

[13] Sleep pattern, healthy lifestyle and colorectal cancer incidence [J].

Chen, Jie ;

Chen, Nanqian ;

Huang, Tao ;

Huang, Ninghao ;

Zhuang, Zhenhuang ;

Liang, Hailun .

SCIENTIFIC REPORTS, 2022, 12 (01)

[14] Circadian Regulator CLOCK Recruits Immune-Suppressive Microglia into the GBM Tumor Microenvironment [J].

Chen, Peiwen ;

Hsu, Wen-Hao ;

Chang, Andrew ;

Tan, Zhi ;

Lan, Zhengdao ;

Zhou, Ashley ;

Spring, Denise J. ;

Lang, Frederick F. ;

Wang, Y. Alan ;

DePinho, Ronald A. .

CANCER DISCOVERY, 2020, 10 (03) :371-381

[15] Prognosis and Immunotherapy Significances of a Cancer-Associated Fibroblasts-Related Gene Signature in Gliomas [J].

Chen, Zhimin ;

Zhuo, Shenghua ;

He, Guiying ;

Tang, Jingzhi ;

Hao, Weijie ;

Gao, Wei-Qiang ;

Yang, Kun ;

Xu, Huiming .

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2021, 9

[16] Health-related quality of life in glioma patients in China [J].

Cheng, Jin-xiang ;

Liu, Bo-lin ;

Zhang, Xiang ;

Lin, Wei ;

Zhang, Yong-qiang ;

Liu, Wei-ping ;

Zhang, Jian-ning ;

Lin, Hong ;

Wang, Rui ;

Yin, Hong .

BMC CANCER, 2010, 10

[17] Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial [J].

Chiocca, E. Antonio ;

Yu, John S. ;

Lukas, Rimas V. ;

Solomon, Isaac H. ;

Ligon, Keith L. ;

Nakashima, Hiroshi ;

Triggs, Daniel A. ;

Reardon, David A. ;

Wen, Patrick ;

Stopa, Brittany M. ;

Naik, Ajay ;

Rudnick, Jeremy ;

Hu, Jethro L. ;

Kumthekar, Priya ;

Yamini, Bakhtiar ;

Buck, Jill Y. ;

Demars, Nathan ;

Barrett, John A. ;

Gelb, Arnold B. ;

Zhou, John ;

Lebel, Francois ;

Cooper, Laurence J. N. .

SCIENCE TRANSLATIONAL MEDICINE, 2019, 11 (505)

[18] Immunotherapy for Glioblastoma: Adoptive T-cell Strategies [J].

Choi, Bryan D. ;

Maus, Marcela V. ;

June, Carl H. ;

Sampson, John H. .

CLINICAL CANCER RESEARCH, 2019, 25 (07) :2042-2048

[19] Microglia in the Brain Tumor Microenvironment [J].

Cole, Allison P. ;

Hoffmeyer, Eric ;

Chetty, Senthilnath Lakshmana ;

Cruz-Cruz, Joselyn ;

Hamrick, Forrest ;

Youssef, Osama ;

Cheshier, Samuel ;

Mitra, Siddhartha S. .

TUMOR MICROENVIRONMENT: HEMATOPOIETIC CELLS, PT B, 2020, 1273 :197-208

[20] A survey of best practices for RNA-seq data analysis [J].

Conesa, Ana ;

Madrigal, Pedro ;

Tarazona, Sonia ;

Gomez-Cabrero, David ;

Cervera, Alejandra ;

McPherson, Andrew ;

Szczesniak, Michal Wojciech ;

Gaffney, Daniel J. ;

Elo, Laura L. ;

Zhang, Xuegong ;

Mortazavi, Ali .

GENOME BIOLOGY, 2016, 17

← 1 2 3 4 5 6 7 8 9 10 →