Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (8): 34-43.doi: 10.6040/j.issn.1671-7554.0.2021.1339

Previous Articles     Next Articles

Construction of a prognostic risk model of pyroptosis-related genes in breast cancer based on database

HE Shiqing1, LI Wanwan1, DONG Shuqing1, MOU Jingyi1, LIU Yuying1, WEI Siyu1, LIU Zhao2, ZHANG Jiaxin2   

  1. 1.Xuzhou Medical University, Xuzhou 221004, Jiangsu, China;
    2. Department of Thyroid and Breast Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, Jingsu, China
  • Published:2022-07-27

Abstract: Objective To explore the prognostic value of pyroptosis-related differentially expressed genes(DEGs)in breast cancer and to construct a prognostic risk model. Methods Gene sequencing and clinical data of breast cancer were downloaded from The Cancer Genome Atlas(TCGA)and Gene Expression Ominibus(GEO)to screen for pyroptosis-related DEGs. A cluster analysis was performed on breast cancer patients. The model of TCGA cohort was established by the least absolute shrinkage and selection operator(LASSO)method, which was then evaluated with Kaplan-Meier survival curve, receiver operating characteristic curve(ROC), univariate and multivariate Cox regression independent prognostic factor analysis. The GEO cohort was used as the validation set. Enrichment of DGEs was analyzed with GO, KEGG, and ssGSEA. Results Pyroptosis-related DEGs were screened, cluster analysis showed that the overall survival(OS)of C2 group was prolonged, and the difference was statistically significant?(P=0.020). K-M survival analysis showed that OS was shortened in the high-risk group(P<0.001 in the TCGA cohort, P=0.018 in the GEO cohort). The area under the ROC curve(AUC)showed that the model had certain predictive ability. Univariate and multivariate Cox regression showed that age, M and N stage, and risk score were independent predictors of OS. GO, KEGG and ssGSEA analyses confirmed that pyroptosis-related DEGs were related to immune inflammatory factors and pathways. Conclusion This study constructed a prognostic risk model of breast cancer composed of 9 pyroptosis-related genes, which can provide reference for the risk and prognosis assessment of breast cancer patients.

Key words: Breast cancer, Pyroptosis, Immunity, Prognosis, Prediction model

CLC Number: 

  • R737.9
[1] Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021 [J]. CACancer J Clin, 2021, 71(1): 7-33.
[2] Britt KL, Cuzick J, Phillips KA. Key steps for effective breast cancer prevention [J]. NatRev Cancer, 2020, 20(8): 417-436.
[3] Barzaman K, Karami J, Zarei Z, et al. Breast cancer: biology, biomarkers, and treatments [J]. Int Immunopharmacol, 2020, 84: 106535. doi: 10.1016/j.intimp.2020.106535.
[4] Liu X, Lieberman J. A mechanistic understanding of pyroptosis: the fiery death triggered by invasive infection [J]. Adv Immunol 2017, 135: 81-117. doi: 10.1016/bs.ai.2017.02.002.
[5] 胡颖超, 杨硕. 细胞焦亡的研究进展[J]. 南京医科大学学报(自然科学版), 2021, 41(8): 1245-1251. HU Yingchao, YANG Shuo. Advance in research of phroptosis [J]. 2021, 41(8): 1245-1251.
[6] Tan Y, Chen Q, Li X, et al. Pyroptosis: a new paradigm of cell death for fighting against cancer [J]. J Exp Clin Cancer Res, 2021, 40(1): 153.
[7] Ni J, Peng Y, Yang FL, et al. Overexpression of CLEC3A promotes tumor progression and poor prognosis in breast invasive ductal cancer [J]. OncoTargets Ther, 2018, 11: 3303-12. doi: 10.2147/OTT.S161311.
[8] Bakaeean B, Gholamin M, Tabatabaee Yazdi SA, et al. Novel biomarkers aim at detecting metastatic sentinel lymph nodes in breast cancer [J]. Iran Biomed J, 2020, 24(3): 183-191.
[9] Ren C, Pan R, Hou L, et al. Suppression of CLEC3A inhibits osteosarcoma cell proliferation and promotes their chemosensitivity through the AKT1/mTOR/HIF1α signaling pathway [J]. Mol Med Rep, 2020, 21(4): 1739-1748.
[10] Tsunezumi J, Higashi S, Miyazaki K. Matrilysin(MMP-7)cleaves C-type lectin domain family 3 member A(CLEC3A)on tumor cell surface and modulates its cell adhesion activity [J]. J Cell Biochem, 2009, 106(4): 693-702.
[11] Miki M, Oono T, Fujimori N, et al. CLEC3A, MMP7, and LCN2 as novel markers for predicting recurrence in resected G1 and G2 pancreatic neuroendocrine tumors [J]. Cancer Med, 2019, 8(8): 3748-3760.
[12] Qi T, Qu J, Tu C, et al. Super-enhancer associated five-gene risk score model predicts overall survival in multiple myeloma patients [J]. Front Cell Dev Biol, 2020, 8: 596777. doi: 10.3389/fcell.2020.596777.
[13] Zhang G, Liu Y, Dong F, et al. Transcription/expression of KLRB1 gene as a prognostic indicator in human esophageal squamous cell carcinoma [J]. Comb Chem High Throughput Screen, 2020, 23(7): 667-674.
[14] Qin R, Cao L, Ye C, et al. A novel prognostic prediction model based on seven immune-related RNAs for predicting overall survival of patients in early cervical squamous cell carcinoma [J]. BMC Med Genomics, 2021, 14(1): 49.
[15] Ma C, Luo H, Cao J, et al. Identification of a novel tumor microenvironment-associated eight-gene signature for prognosis prediction in lung adenocarcinoma [J]. Front Mol Biosci, 2020, 7: 571641. doi: 10.3389/fmolb.2020.571641.
[16] Zheng M, Mullikin H, Hester A, et al. Development and validation of a novel 11-gene prognostic model for serous ovarian carcinomas based on lipid metabolism expression profile [J]. Int J Mol Sci, 2020, 21(23): 9169.
[17] Zhang Y, Di X, Chen G, et al. An immune-related signature that to improve prognosis prediction of breast cancer [J]. Am J Cancer Res, 2021, 11(4): 1267-1285.
[18] Park YJ, Ryu H, Choi G, et al. IL-27 confers a protumorigenic activity of regulatory T cells via CD39 [J]. Proc Natl Acad Sci U S A, 2019, 116(8): 3106-3111.
[19] Wang L, Liu J, Tai J, et al. A prospective study revealing the role of an immune-related eRNA, WAKMAR2, in breast cancer [J]. Sci Rep, 2021, 11(1): 15328.
[20] Ignacio RMC, Gibbs CR, Kim S, et al. Serum amyloid A predisposes inflammatory tumor microenvironment in triple negative breast cancer [J]. Oncotarget, 2019, 10(4): 511-526.
[21] Jiao J, Jiang L, Luo Y. N6-methyladenosine-related RNA signature predicting the prognosis of ovarian cancer [J]. Recent Pat Anticancer Drug Discov, 2021, 16(3): 407-416.
[22] Liang J, Zhao W, Tong P, et al. Comprehensive molecular characterization of inhibitors of apoptosis proteins(IAPs)for therapeutic targeting in cancer [J]. BMC Med Genomics, 2020, 13(1): 7.
[23] Cao C, Lin S, Zhi W, et al. LOXL2 expression status is correlated with molecular characterizations of cervical carcinoma and associated with poor cancer survival via epithelial-mesenchymal transition(EMT)phenotype [J]. Front Oncol, 2020, 10: 284. doi: 10.3389/fonc.2020.00284.
[24] Shahi P, Wang CY, Chou J, et al. GATA3 targets semaphorin 3B in mammary epithelial cells to suppress breast cancer progression and metastasis [J]. Oncogene, 2017, 36(40): 5567-5575.
[25] Milioli HH, Sousa KS, Kaviski R, et al. Comparative proteomics of primary breast carcinomas and lymph node metastases outlining markers of tumor invasion [J]. Cancer Genomics Proteomics, 2015, 12(2): 89-101.
[1] Yun LIN,Yanqiu XIE. Fertility protection and preservation in breast cancer patients [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 42-46.
[2] ZHENG Su, CHEN Shuhua, LI Hua, DENG Jie, CHEN Chunhong, WANG Xiaohui, FENG Weixing, HAN Xiaodi, ZHANG Yujia, LI Na, LI Mo, FANG Fang. Correlation between EEG variations and BASED evaluation of the efficacy of ACTH treatment in 54 cases of infantile spasms [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 91-96.
[3] WANG Lihui, GAO Min, KONG Beihua. Angiosarcoma of the uterus: a report of 2 cases and literature review [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 108-112.
[4] YANG Qifeng, ZHANG Ning. Sentinel lymph node biopsy of breast cancer in the era of precision medicine [J]. Journal of Shandong University (Health Sciences), 2022, 60(8): 1-5.
[5] ZHANG Yufeng, XU Min, XING Xiuli, PANG Shuguang, HU Keqing. Epidemiological characteristics of 689 patients with non-ST-segment elevation myocardial infarction [J]. Journal of Shandong University (Health Sciences), 2022, 60(7): 118-122.
[6] LI Linlin, WANG Kai. Prediction of hepatocellular carcinoma prognostic genes based on bioinformatics [J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 50-58.
[7] ZHAO Tingting, QI Yana, ZHANG Ying, YUAN Bing, HAN Mingyong. Mouse breast cancer induces changes of the microenvironment in pre-metastatic lung tissue [J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 24-29.
[8] SUN Zhenguo, TIAN Hui. Optimization of the procedures in minimally invasive esophagectomy: the Qilu practices [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 33-37.
[9] ZHU Yongcun, ZHAO Xiushi, SUN Nannan, YAO Zhigang, ZHOU Xingchen, MU Kun. Prostate clear cell adenocarcinomas: a report of 3 cases and literature review [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 102-107.
[10] SHI Xiaohan, LI Huayu, LI Feng. Prognostic factors of elderly patients with glioblastoma treated with Stupp treatment [J]. Journal of Shandong University (Health Sciences), 2022, 60(10): 42-48.
[11] FENG Haigang, LIU Guowen, CAO Hong. Effects and mechanism of interfering MAD2L1 gene expression on the apoptosis of breast cancer cells [J]. Journal of Shandong University (Health Sciences), 2022, 60(10): 9-16.
[12] CHU Zhuxiu, ZHAO Wenjing, LI Xiaoyan, KONG Xiaoli, MA Tingting, JIANG Liyu, YANG Qifeng. Significance of neoadjuvant chemotherapy and molecular marker changes in 218 women with breast cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 130-139.
[13] GE Shaohua, DING Tian, LIU Hongrui. Role and regulatory mechanism of type 2 immunity in tissue repair [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 51-56.
[14] WANG Zhe, LIU Yujie, MAO Qian, GUAN Peixia, BAO Qihan, LI Chengsheng, QIAO Xiaowei, PAN Qingzhong, WANG Suzhen. Evaluation of the efficacy of different regimens for early triple negative breast cancer based on the inverse probability of treatment weighting method [J]. Journal of Shandong University (Health Sciences), 2021, 59(8): 113-118.
[15] CHU Yan, LIU Duanrui, ZHU Wenshuai, FAN Rong, MA Xiaoli, WANG Yunshan, JIA Yanfei. Expressions of DNA methyltransferases in gastric cancer and their clinical significance [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 1-9.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] MA Qingyuan, PU Peidong, HAN Fei, WANG Chao, ZHU Zhoujun, WANG Weishan, SHI Chenhui. Effect of miR-27b-3p regulating SMAD1 on osteosarcoma cell proliferation, migration and invasion[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 32 -37 .
[2] SUO Dongyang, SHEN Fei, GUO Hao, LIU Lichang, YANG Huimin, YANG Xiangdong. Expression and mechanism of Tim-3 in animal model of drug-induced acute kidney injury[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 1 -6 .
[3] ZHANG Baowen, LEI Xiangli, LI Jinna, LUO Xiangjun, ZOU Rong. miR-21-5p targeted TIMP3 to inhibit proliferation and extracellular matrix accumulation of mesangial cells in Type II diabetic nephropathy mice[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 7 -14 .
[4] FU Jieqi, ZHANG Man, ZHANG Xiaolu, LI Hui, CHEN Hong. Molecular mechanism of Toll-like receptor 4 in the aggravation of blood lipid accumulation by inhibiting the peroxisome proliferator-activate receptor γ[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 24 -31 .
[5] LONG Tingting, XIE Ming, ZHOU Lu, ZHU Junde. Effect of Noggin protein on learning and memory abilities and the dentate gyrus structure after cerebral ischemia reperfusion injury in mice[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 15 -23 .
[6] LI Ning, LI Juan, XIE Yan, LI Peilong, WANG Yunshan, DU Lutao, WANG Chuanxin. Expression of LncRNA AL109955.1 in 80 cases of colorectal cancer and its effect on cell proliferation, migration and invasion[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 38 -46 .
[7] DING Xiangyun, YU Qingmei, ZHANG Wenfang, ZHUANG Yuan, HAO Jing. Correlation of the expression of insulin-like growth factor II in granulosa cells and ovulation induction outcomes of 84 patients with polycystic ovary syndrome[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 60 -66 .
[8] XU Yuxiang, LIU Yudong, ZHANG Peng, DUAN Ruisheng. A retrospective analysis of risk factors of cerebral microbleeds in 101 patients with cerebral small vessel disease[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 67 -71 .
[9] XIAO Juan, XIAO Qiang, CONG Wei, LI Ting, DING Shouluan, ZHANG Yuan, SHAO Chunchun, WU Mei, LIU Jianing, JIA Hongying. Comparison of diagnostic efficacy of two kinds of thyroid imagine reporting and data systems[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 53 -59 .
[10] SHI Shuang, LI Juan, MI Qi, WANG Yunshan, DU Lutao, WANG Chuanxin. Construction and application of a miRNAs prognostic risk assessment model of gastric cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 47 -52 .