Study on the gene related to bone metastasis of breast cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HE Gongjian ¹ ,  DU Zhenggui ²

1. Department of Breast, Thyroid, and Burn Disease, Guang’an People’s Hospital, Guang’an, Sichuan 638001, P. R. China;
2. Department of Breast Surgery, West China Hospital of Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

DU Zhenggui, Email: docduzg@163.com

Keywords：

breast cancer; bone metastasis; weighted gene co-expression network analysis; hub gene

DOI：

10.7507/1007-9424.201912069

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To find the hub genes related to bone metastasis of breast cancer by weighted geneco-expression network analysis (WGCNA) method, and provide theoretical support for the development of new targeted therapeutic drugs.Methods The basic clinical features of 286 breast cancer patients and the gene expression information of tumor specimens were downloaded from the GSE2034 dataset from the Gene Expression Omnibus. R software was used to analyze the gene microarray. The WGCNA package embedded in the R software was used for various analysis in weighted correlation network analysis. Cox proportional hazard regression was performed by using SPSS software.Results The top one quarter genes with the greatest variance variability were selected by WGCNA, and a total of 5 000 genes were used for further enrichment analysis. Finally, 15 gene co-expression modules were constructed, and the magenta module (r=0.94, P<0.001) was significantly positively correlated with bone metastasis of breast cancer. It was further found that six hub genes highly associated with bone metastasis in the magenta module were: Ral GTPase-activating protein subunitalpha-1 (RALGAPA1), B-cell antigen receptor complex-associated protein alpha chain (CD79A), immunoglobulin kappa chain C region (IGKC), arrestin beta 2 (ARRB2), differentially expressed in FDCP 6 homolog (DEF6), and immunoglobulin lambda variable 2 (IGLV2).Conclusion We found that RALGAPA1, CD79A, IGKC, ARRB2. DEF6, and IGLV2 may play an important role in bone metastasis of breast cancer.

Citation： HE Gongjian, DU Zhenggui. Study on the gene related to bone metastasis of breast cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(10): 1254-1258. doi: 10.7507/1007-9424.201912069 Copy

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19.	Sloan EK, Priceman SJ, Cox BF, <italic>et al</italic>. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res, 2010, 70(18): 7042-7052.
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21.	Binder N, Miller C, Yoshida M, <italic>et al</italic>. Def6 restrains osteoclastogenesis and inflammatory bone resorption. J Immunol, 2017, 198(9): 3436-3447.
22.	Zhang Y, He W, Zhang S. Seeking for correlative genes and signaling pathways with bone metastasis from breast cancer by integrated analysis. Front Oncol, 2019, 9: 138.
23.	Masannat J, Purayil HT, Zhang Y, <italic>et al</italic>. βarrestin2 mediates renal cell carcinoma tumor growth. Sci Rep, 2018, 8(1): 4879.
24.	Ren W, Wang T, He X, <italic>et al</italic>. β-arrestin2 promotes 5-FU-induced apoptosis <italic>via</italic> the NF-κB pathway in colorectal cancer. Oncol Rep, 2018, 39(6): 2711-2720.
25.	Sun WY, Hu SS, Wu JJ, <italic>et al</italic>. Down-regulation of β-arrestin2 promotes tumour invasion and indicates poor prognosis of hepatocellular carcinoma. Sci Rep, 2016, 6: 35609.
26.	Cong L, Qiu ZY, Zhao Y, <italic>et al</italic>. Loss of β-arrestin-2 and activation of CXCR2 correlate with lymph node metastasis in non-small cell lung cancer. J Cancer, 2017, 8(14): 2785-2792.

1. Kennecke H, Yerushalmi R, Woods R, <italic>et al</italic>. Metastatic behavior of breast cancer subtypes. J Clin Oncol, 2010, 28(20): 3271-3277.
2. Wang CY, Wu GY, Shen MJ, <italic>et al</italic>. Comparison of distribution characteristics of metastatic bone lesions between breast and prostate carcinomas. Oncol Lett, 2013, 5(1): 391-397.
3. Charhon SA, Chapuy MC, Delvin EE, <italic>et al</italic>. Histomorphometric analysis of sclerotic bone metastases from prostatic carcinoma special reference to osteomalacia. Cancer, 1983, 51(5): 918-924.
4. Tulotta C, Lefley DV, Freeman K, <italic>et al</italic>. Endogenous production of IL1B by breast cancer cells drives metastasis and colonization of the bone microenvironment. Clin Cancer Res, 2019, 25(9): 2769-2782.
5. Nakai Y, Okamoto K, Terashima A, <italic>et al</italic>. Efficacy of an orally active small-molecule inhibitor of RANKL in bone metastasis. Bone Res, 2019, 7: 1.
6. Cao Q, Chen X, Wu X, <italic>et al</italic>. Inhibition of UGT8 suppresses basal-like breast cancer progression by attenuating sulfatide-αVβ5 axis. J Exp Med, 2018, 215(6): 1679-1692.
7. Zhuang X, Zhang H, Li X, <italic>et al</italic>. Differential effects on lung and bone metastasis of breast cancer by Wnt signalling inhibitor DKK1. Nat Cell Biol, 2017, 19(10): 1274-1285.
8. Bakhtiarizadeh MR, Hosseinpour B, Shahhoseini M, <italic>et al</italic>. Weighted gene co-expression network analysis of endometriosis and identification of functional modules associated with its main hallmarks. Front Genet, 2018, 9: 453.
9. Giulietti M, Occhipinti G, Principato G, <italic>et al</italic>. Identification of candidate miRNA biomarkers for pancreatic ductal adenocarcinoma by weighted gene co-expression network analysis. Cell Oncol (Dordr), 2017, 40(2): 181-192.
10. Liang JW, Fang ZY, Huang Y, <italic>et al</italic>. Application of weighted gene co-expression network analysis to explore the key genes in Alzheimer’s disease. J Alzheimers Dis, 2018, 65(4): 1353-1364.
11. Yan C, Theodorescu D. RAL GTPases: biology and potential as therapeutic targets in cancer. Pharmacol Rev, 2018, 70(1): 1-11.
12. Chen Q, Quan C, Xie B, <italic>et al</italic>. GARNL1, a major RalGAP α subunit in skeletal muscle, regulates insulin-stimulated RalA activation and GLUT4 trafficking <italic>via</italic> interaction with 14-3-3 proteins. Cell Signal, 2014, 26(8): 1636-1648.
13. Wu Z, Owens C, Chandra N, <italic>et al</italic>. RalBP1 is necessary for metastasis of human cancer cell lines. Neoplasia, 2010, 12(12): 1003-1012.
14. Taubenberger AV. <italic>In vitro</italic> microenvironments to study breast cancer bone colonisation. Adv Drug Deliv Rev, 2014, 79-80: 135-144.
15. Luger D, Yang YA, Raviv A, <italic>et al</italic>. Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects. PLoS One, 2013, 8(10): e76115.
16. Harmer D, Falank C, Reagan MR. Interleukin-6 interweaves the bone marrow microenvironment, bone loss, and multiple myeloma. Front Endocrinol (Lausanne), 2019, 9: 788.
17. Groot Kormelink T, Powe DG, Kuijpers SA, <italic>et al</italic>. Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation. Oncotarget, 2014, 5(10): 3159-3167.
18. Khan MW, Keshavarzian A, Gounaris E, <italic>et al</italic>. PI3K/AKT signaling is essential for communication between tissue-infiltrating mast cells, macrophages, and epithelial cells in colitis-induced cancer. Clin Cancer Res, 2013, 19(9): 2342-2354.
19. Sloan EK, Priceman SJ, Cox BF, <italic>et al</italic>. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res, 2010, 70(18): 7042-7052.
20. Leibbrandt A, Penninger JM. RANKL/RANK as key factors for osteoclast development and bone loss in arthropathies. Adv Exp Med Biol, 2009, 649: 100-113.
21. Binder N, Miller C, Yoshida M, <italic>et al</italic>. Def6 restrains osteoclastogenesis and inflammatory bone resorption. J Immunol, 2017, 198(9): 3436-3447.
22. Zhang Y, He W, Zhang S. Seeking for correlative genes and signaling pathways with bone metastasis from breast cancer by integrated analysis. Front Oncol, 2019, 9: 138.
23. Masannat J, Purayil HT, Zhang Y, <italic>et al</italic>. βarrestin2 mediates renal cell carcinoma tumor growth. Sci Rep, 2018, 8(1): 4879.
24. Ren W, Wang T, He X, <italic>et al</italic>. β-arrestin2 promotes 5-FU-induced apoptosis <italic>via</italic> the NF-κB pathway in colorectal cancer. Oncol Rep, 2018, 39(6): 2711-2720.
25. Sun WY, Hu SS, Wu JJ, <italic>et al</italic>. Down-regulation of β-arrestin2 promotes tumour invasion and indicates poor prognosis of hepatocellular carcinoma. Sci Rep, 2016, 6: 35609.
26. Cong L, Qiu ZY, Zhao Y, <italic>et al</italic>. Loss of β-arrestin-2 and activation of CXCR2 correlate with lymph node metastasis in non-small cell lung cancer. J Cancer, 2017, 8(14): 2785-2792.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study on the gene related to bone metastasis of breast cancer

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