BATF2 gene expression in breast cancer samples and its association with clinical factors and patients' survival

Document Type : Original Article

Authors

1 PhD student in Veterinary Medicine, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

2 Assistant professor, Department of Genetics, School of Basic Sciences, Shahrekord University, Shahrekord, Iran.

Abstract

Introduction: BATF2 (Basic leucine zipper transcription factor 2) is related to some cancer types, and dysregulation of BATF2 expression is frequently detected in aggressive and metastatic cancers. The expression of BATF2 was revealed to inhibit the development of malignant tumor cells and decreased expression of BATF2 has been correlated to poor prognosis in different cancer. However, the role of BATF2 in breast cancer has been less known. Therefore, this study was performed with aim to investigate the BATF2 gene expression in breast cancer.
Methods: In this case-control study which was performed in 2016-2018, 40 formalin-fixed paraffin-embedded breast cancer tissues and 40 adjacent non-tumor tissues were evaluated. After total RNA extraction and cDNA synthesis, relative gene expression was accomplished by Real-Time PCR and evaluated by  method. Also, the association of gene expression with clinical factors and survival rate was evaluated. Data were analyzed by SPSS statistical software (version 22) and T and ANOVA tests. p < 0.05 was considered statistically significant.
Results: BATF2 expression was significantly decreased in the breast tumor tissues compared with the non-tumor tissues (P=0.0001). Consistent with these results, BATF2 expression was correlated with metastasis and high tumor grade (P= 0.008 and P=0.01, respectively). As well as, decreased BATF2 expression showed reduced overall survival when compared to those with high expression (P=0.03).
Conclusion: BATF2 plays a tumor-suppressor role in the development of breast cancer. Also, decreased BATF2 expression is associated with the metastasis as well as poor prognosis of cancer. Therefore, BATF2 may serve as a prognostic biomarker and potential therapeutic target for this disease. However, further investigation is needed to validate this claim.

Keywords


  1. Akram M, Iqbal M, Daniyal M, Khan AU. Awareness and current knowledge of breast cancer. Biol Res 2017; 50(1):33.
  2. DeSantis CE, Fedewa SA, Goding Sauer A, Kramer JL, Smith RA, Jemal A. Breast cancer statistics, 2015: Convergence of incidence rates between black and white women. CA Cancer J Clin 2016; 66(1):31-42.
  3. Knight JA, Fan J, Malone KE, John EM, Lynch CF, Langballe R, et al. Alcohol consumption and cigarette smoking in combination: A predictor of contralateral breast cancer risk in the WECARE study. Int J Cancer 2017; 141(5):916-24.
  4. McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ 2000; 321(7261):624-8.
  5. Karami F, Mehdipour P. A comprehensive focus on global spectrum of BRCA1 and BRCA2 mutations in breast cancer. Biomed Res Int 2013; 2013:928562.
  6. Vallejos CS, Gómez HL, Cruz WR, Pinto JA, Dyer RR, Velarde R, et al. Breast cancer classification according to immunohistochemistry markers: subtypes and association with clinicopathologic variables in a peruvian hospital database. Clin Breast Cancer 2010; 10(4):294-300.
  7. Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 2009; 101(10):736-50.
  8. Dunn BK, Wagner PD, Anderson D, Greenwald P. Molecular markers for early detection. Semin Oncol 2010; 37(3):224-42.
  9. DeVita VT, Hellman S, Rosenberg SA. Cancer: principles and practice of oncology. 6nd ed. Lippincott Williams & Wilkins; 2001.
  10. Su ZZ, Lee SG, Emdad L, Lebdeva IV, Gupta P, Valerie K, et al. Cloning and characterization of SARI (suppressor of AP-1, regulated by IFN). Proceedings of the National Academy of Sciences of the United States of America 2008; 105(52):20906-11.
  11. Betz BC, Jordan-Williams KL, Wang C, Kang SG, Liao J, Logan MR, et al. Batf coordinates multiple aspects of B and T cell function required for normal antibody responses. J Exp Med 2010; 207(5):933-42.
  12. Tussiwand R, Lee WL, Murphy TL, Mashayekhi M, KC W, Albring JC, et al. Compensatory dendritic cell development mediated by BATF–IRF interactions. Nature 2012; 490(7421):502-7.
  13. Kanemaru H, Yamane F, Fukushima K, Matsuki T, Kawasaki T, Ebina I, et al. Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages. Proc Natl Acad Sci U S A 2017; 114(35):E7331-E40.
  14. Wang C, Su Y, Zhang L, Wang M, You J, Zhao X, et al. The function of SARI in modulating epithelial-mesenchymal transition and lung adenocarcinoma metastasis. PloS One 2012; 7(9):e38046.
  15. Dai L, Cui X, Zhang X, Cheng L, Liu Y, Yang Y, et al. SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin. Nat Commun 2016; 7:11996.
  16. Liu ZB, Yang Y, Ye XG, Wang L, Tian PY, Zhang YY. Expression and significance of SARI and CCN1 in human colorectal carcinomas. Zhonghua Yi Xue Za Zhi 2011; 91(34):2397-401.
  17. Ma H, Liang X, Chen Y, Pan K, Sun J, Wang H, et al. Decreased expression of BATF2 is associated with a poor prognosis in hepatocellular carcinoma. Int J Cancer 2011; 128(4):771-7.
  18. Nurozpour Mamasani M, Reiisi S, Peymani M. Down-regulation of BACH2 in formalin-fixed paraffin-embedded breast cancer tissue as transcriptional regulation in cancer. Iran J Obstet Gynecol Infertil 2017; 20(10):105-113.
  19. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 2001; 25(4):402-8.
  20. Kurachi M, Barnitz RA, Yosef N, Odorizzi PM, DiIorio MA, Lemieux ME, et al. The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells. Nat Immunol 2014; 15(4):373-83.
  21. Roy S, Guler R, Parihar SP, Schmeier S, Kaczkowski B, Nishimura H, et al. Batf2/Irf1 induces inflammatory responses in classically activated macrophages, lipopolysaccharides, and mycobacterial infection. J Immunol 2015; 194(12):6035-44.
  22. Liu Z, Wei P, Yang Y, Cui W, Cao B, Tan C, et al. BATF2 deficiency promotes progression in human colorectal cancer via activation of HGF/MET signaling: a potential rationale for combining MET inhibitors with IFNs. Clin Cancer Res 2015; 21(7):1752-63.
  23. Dash R, Su ZZ, Lee SG, Azab B, Boukerche H, Sarkar D, et al. Inhibition of AP-1 by SARI negatively regulates transformation progression mediated by CCN1. Oncogene 2010; 29(31):4412-23.
  24. Yang W, Wu B, Ma N, Wang Y, Guo J, Zhu J, et al. BATF2 reverses multidrug resistance of human gastric cancer cells by suppressing Wnt/β-catenin signaling. In Vitro Cell Dev Biol Anim 2019: 55(6):445-52.
  25. Zhou RJ, Shi Z, Zhou K, Wang HD, Zhang GQ, Li XT, et al. Decreased SARI expression predicts poor prognosis of Chinese patients with non-small cell lung cancer. Int J Clin Exp Pathol 2013; 6(10):2056-63.
  26. Wen H, Chen Y, Hu Z, Mo Q, Tang J, Sun C. Decreased expression of BATF2 is significantly associated with poor prognosis in oral tongue squamous cell carcinoma. Oncol Rep 2014; 31(1):169-74.