基于TCGA数据库代谢相关基因构建乳腺癌预后模型

doi:10.11904/j.issn.1002-3070.2022.01.007

Abstract

Abstract: Objective The aims of this study were to construct a breast cancer metabolism-related prognostic model based on the TCGA database,and to reveal the relationship between metabolism and breast cancer prognosis.Methods Metabolism related genes were retrieved from KEGG database,and limma package was used to screen metabolism-related differential genes of 1109 breast cancer samples and 113 normal controls in the TCGA database.The 70% of samples were randomly selected as the training set,and the remaining 30% of the samples were used as the validation set.Univariate Cox regression was used to screen prognosis-related genes,a metabolism-related prognostic model was constructed based on glmnet package,and the model was validated by univariate and multivariate Cox regression.Results In this study,168 metabolically related differential genes were screened.After survival filtering and overfitted genes were removed,13 metabolically related genes were finally used for the construction of prognostic model,including NMNAT2、NT5E、QPRT、UGP2、MTHFD2、TSTA3、TYMP、ALDH2、ALDH1A1、IDO1、IL4I1、INPP1 and ENPP6.Survival analysis showed that the survival time of patients in the high-risk group was significantly longer than that in the low-risk group(P＜0.05).Univariate and multivariate Cox regression results indicated that the risk score of the constructed metabolism related prognostic model was an independent prognostic factor for breast cancer patients.Conclusion The prognostic model constructed in this study revealed the relationship between metabolism and breast cancer prognosis,and provided a new perspective for breast cancer diagnosis and research of breast cancer.

Key words: Breast cancer, Metabolism-related genes, Prediction model, Gene signature, Prognosis

CLC Number:

R737.9

LI Weihua, ZHANG Guangfeng, MA Lili, HE Pin, WANG Wen, LI Dingfu. Construction of a breast cancer prognostic model based on metabolism-related genes in the TCGA database[J]. Journal of Practical Oncology, 2022, 36(1): 37-43.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/10.11904/j.issn.1002-3070.2022.01.007

http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/Y2022/V36/I1/37

References

1 Siegel RL,Miller KD,Jemal A.Cancer statistics,2020[J].CA Cancer J Clin,2020,70(1):7-30.
2 Provenzano E,Ulaner GA,Chin SF.Molecular classification of breast cancer[J].PET Clin,2018,13(3):325-338.
3 Wang X,Sun C,Huang X et al.The advancing roles of exosomes in breast cancer[J].Front Cell Dev Biol,2021,9:731062.
4 Zhao L,Mao Y,Zhao Y et al.Role of multifaceted regulators in cancer glucose metabolism and their clinical significance[J].Oncotarget,2016,7(21):31572-31585.
5 Im YK,Najyb O,Gravel SP et al.Interplay between ShcA signaling and PGC-1alpha triggers targetable metabolic vulnerabilities in breast cancer[J].Cancer Res,2018,78(17):4826-4838.
6 Reznik E,Sander C.Extensive decoupling of metabolic genes in cancer[J].PLoS Comput Biol,2015,11(5):e1004176.
7 Lukacs M,Gilley J,Zhu Y et al.Severe biallelic loss-of-function mutations in nicotinamide mononucleotide adenylyltransferase 2(NMNAT2)in two fetuses with fetal akinesia deformation sequence[J].Exp Neurol,2019,320:112961.
8 Liu Z,Cheng Y,Luan Y et al.Short-term tamoxifen treatment has long-term effects on metabolism in high-fat diet-fed mice with involvement of Nmnat2 in POMC neurons[J].FEBS Lett,2018,592(19):3305-3316.
9 Jeong YJ,Oh HK,Choi HR et al.Methylation of the NT5E gene Is associated with poor prognostic factors in breast cancer[J].Diagnostics(Basel),2020,10(11):939.
10 Nevedomskaya E,Perryman R,Solanki S et al.A systems oncology approach identifies NT5E as a key metabolic regulator in tumor cells and modulator of platinum sensitivity[J].J Proteome Res,2016,15(1):280-290.
11 Youn HS,Kim TG,Kim MK,et al.Structural insights into the quaternary catalytic mechanism of hexameric human quinolinate phosphoribosyltransferase,a key enzyme in de novo NAD biosynthesis[J].Sci Rep,2016,6:19681.
12 Yue Z,Shusheng J,Hongtao S et al.Silencing DSCAM-AS1 suppresses the growth and invasion of ER-positive breast cancer cells by downregulating both DCTPP1 and QPRT[J].Aging(Albany NY),2020,12(14):14754-14774.
13 Mohammad MA,Hadsell DL,Haymond MW.Gene regulation of UDP-galactose synthesis and transport:potential rate-limiting processes in initiation of milk production in humans[J].Am J Physiol Endocrinol Metab,2012,303(3):365-376.
14 Nilsson R,Jain M,Madhusudhan N,et al.Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer[J].Nat Commun,2014,5:3128.
15 Becker DJ,Lowe JB.Fucose:biosynthesis and biological function in mammals[J].Glycobiology,2003,13(7):41-53.
16 Sun Y,Liu X,Zhang Q,et al.Oncogenic potential of TSTA3 in breast cancer and its regulation by the tumor suppressors miR-125a-5p and miR-125b[J].Tumour Biol,2016,37(4):4963-4972.
17 Marangoni E,Laurent C,Coussy F et al.Capecitabine efficacy is correlated with TYMP and RB1 expression in PDX established from triple-negative breast cancers[J].Clin Cancer Res,2018,24(11):2605-2615.
18 Ugai T,Milne RL,Ito H,et al.The functional ALDH2 polymorphism is associated with breast cancer risk:A pooled analysis from the breast cancer association consortium[J].Mol Genet Genomic Med,2019,7(6):e707.
19 Yang D,Krois CR,Huang P,et al.Raldh1 promotes adiposity during adolescence independently of retinal signaling[J].PLoS One,2017,12(11):e0187669.
20 Liu C,Qiang J,Deng Q,et al.ALDH1A1 activity in tumor-initiating cells remodels myeloid-derived suppressor cells to promote breast cancer progression[J].Cancer Res,2021,81(23):5919-5934.
21 Feng X,Tang R,Zhang R,et al.A comprehensive analysis of IDO1 expression with tumour-infiltrating immune cells and mutation burden in gynaecologic and breast cancers[J].J Cell Mol Med,2020,24(9):5238-5248.
22 Xu T,Liu J,Xia Y,et al.Integrated analysis reveals the participation of IL4I1,ITGB7,and FUT7 in reshaping the TNBC immune microenvironment by targeting glycolysis[J].Ann Med,2021,53(1):916-928.
23 Li SR,Gyselman VG,Lalude O,et al.Transcription of the inositol polyphosphate 1-phosphatase gene(INPP1)is upregulated in human colorectal cancer[J].Mol Carcinog,2000,27(4):322-329.
24 Sakagami H,Aoki J,Natori Y,et al.Biochemical and molecular characterization of a novel choline-specific glycerophosphodiester phosphodiesterase belonging to the nucleotide pyrophosphatase/phosphodiesterase family[J].J Biol Chem,2005,280(24):23084-23093.

[1]	WANG Yuping, SI Meili, SUN Xiaoxia, GUO Yulin. High expression of HPIP in endometrial carcinoma and its significance in the analysis of survival and prognosis [J]. Journal of Practical Oncology, 2022, 36(1): 44-48.
[2]	CAO Shiyu, JIANG Yongdong. The influence of gene expression,polygene detection and biomarkers on the prognosis of Luminal A-like breast cancer [J]. Journal of Practical Oncology, 2022, 36(1): 89-93.
[3]	WANG Lina, WANG Le, JIN Hong, LI Qi, CHENG Haiyan. The expression of UBQLN1 in cervical cancer and its effect on prognosis [J]. Journal of Practical Oncology, 2021, 35(6): 506-510.
[4]	CHEN Yixin, SUN Yihua, CHENG Yangyang, HE Kaitong, GUO Ting. Relationship between preoperative inflammation-related indicators and prognosis of patients with resectable gastric cancer [J]. Journal of Practical Oncology, 2021, 35(6): 517-522.
[5]	LUO Bo, ZHANG Qu, ZHENG Hongmei, LIANG Xinjun, ZHOU Xiaomei, WU Xinhong. Efficacy and prognosis of SRT combined with lapatinib in the treatment of HER2-positive breast cancer brain metastasis [J]. Journal of Practical Oncology, 2021, 35(6): 523-528.
[6]	SHI Runze, LI Zhigao. Research progress of precision medical strategy for different subtypes of triple negative breast cancer [J]. Journal of Practical Oncology, 2021, 35(6): 529-533.
[7]	LI Xiang, HU Yang, ZHANG Qingyuan. Research progress of tumor mutational burden as an emerging biomarker for breast cancer immunotherapy [J]. Journal of Practical Oncology, 2021, 35(6): 568-571.
[8]	ZHOU Tianhong, GU Xiuying, YAO Fang, SONG Shuming. Analysis for screening results of breast cancer in Urumqi from 2014 to 2018 [J]. Journal of Practical Oncology, 2021, 35(5): 391-395.
[9]	LU Junrong, WANG Huiwen, HE Dongfeng. Significance of high expression of SALL4 in clinicopathological and prognostic judgment of esophageal squamous cell carcinoma [J]. Journal of Practical Oncology, 2021, 35(5): 420-425.
[10]	MA Buhuan¹, LIU Caixia². Research progress of Jagged1 promoting the occurrence,development and distant metastasis of breast cancer [J]. Journal of Practical Oncology, 2021, 35(5): 452-457.
[11]	QIN Chao, LI Jiang, ZHENG Yadi, WANG Fei, CAO Wei, XU Yongjie, YU Yiwen, ZHAO Liang, YU Xinyang, CHEN Hongda, REN Jiansong, WANG Yong, LI Jing, LI Ni, CHEN Wanqing. Analysis of screening compliance and related factors in high-risk populations of breast cancer in Chinese cities [J]. Journal of Practical Oncology, 2021, 35(4): 291-296.
[12]	GUO Lanwei, ZHANG Shaokai, LIU Shuzheng, ZHENG Liyang, CHEN Qiong, CAO Xiaoqin, SUN Xibin, ZHANG Jiangong. Analysis of compliance with breast cancer screening and its influencing factors in urban areas of Henan province [J]. Journal of Practical Oncology, 2021, 35(4): 307-313.
[13]	YU Youlin, YU Junlin, HU Chaohua, SHEN Xiongshan, LI Weimin, LU Ting, YANG Feng, YANG Qingqing, LIU Chenhao. Analysis for clinical prognostic value of LAYN in thyroid cancer and its influence on infiltration of immune cells [J]. Journal of Practical Oncology, 2021, 35(4): 357-364.
[14]	LIU Wen, QIAO Wenbo. Clinical research status of programmed cell death protein-1 and its ligand in colorectal cancer [J]. Journal of Practical Oncology, 2021, 35(4): 370-375.
[15]	DONG Xiaoping, ZHANG Xue, GUO Dongli, HE Yutong. Research progress on the related factors affecting the prognosis of squamous cell carcinoma of lung [J]. Journal of Practical Oncology, 2021, 35(4): 380-385.

Construction of a breast cancer prognostic model based on metabolism-related genes in the TCGA database

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments