In Silico Study Predicts CCDC69 as a Novel Tumour Suppressor Gene in HER2+ Breast Cancer

Animesh Chowdhury (National Institute of Biomedical Genomics.)

Article ID: 1578

DOI: https://doi.org/10.30564/jhp.v1i2.1578

Abstract


Differential gene expression analysis using databases followed by overall survival (OS) analysis is currently used to identify different oncogenes and tumour suppressor genes. The present study identified coiled coiled domain containing protein 69 (CCDC69) as a tumour suppressor gene in breast cancer by differential gene expression analysis using TCGA dataset for breast adenocarcinoma (BRCA) followed by OS and relapse free survival (RFS) analysis using Kaplan Meier (KM) plotter tool. CCDC69 was observed to be down regulated in tumour of breast cancer patients in BRCA. Following OS analysis for different breast cancer sub-types, low expression of CCDC69 has been observed to be associated with poor survival in HER2+ breast cancer only. CCDC69 was also found to be down regulated in different HER2+ breast cancer cells by analysing Gene Expression Omnibus (GEO) database. Additionally, CCDC69 was found to be under expressed in single cell HER2 positive population, which is evident from the single cell expression ATLAS database. Furthermore, CCDC69 has been observed to be lowly expressed with overexpression of HER2 in breast cancer by co-expression study. The possible mechanism of CCDC69 down regulation in HER2+ breast cancer was resolved using P-SCAN tool. P-SCAN analysis suggested a group of transcription factors (TFs) among which androgen receptor (AR) has been selected as the probable TF that could play a role in CCDC69 down regulation in HER2+ breast cancer. Moreover, overexpression of AR has been observed in BRCA and HER2+ single cell population. AR has also been observed to be co-expressed positively with HER2, but negatively with CCDC69 in breast cancer. Down regulation of CCDC69 can be predicted to stabilize microtubule formation following stimulation of cell growth and cell migration leading to HER2+ breast cancer progression and metastasis.

  


Keywords


Tumor suppressor gene; Overall survival; Relapse free survival; Differential gene expression; Breast cancer

Full Text:

PDF

References


[1] McAnena, P.F., McGuire, A., Ramli, A., Curran, C., Malone, C., McLaughlin, R., Barry, K., Brown, J.A.L., Kerin, M.J., Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options, BMC Cancer, 2018, 18(18): 203.

[2] Edge, S.B., Compton, C.C., The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM, 2010, Ann. Surg. Oncol, 2010, 17: 1471–1474.

[3] Ke, X., Shen, L., Molecular targeted therapy of cancer: The progress and future prospect, Frontiers in Laboratory Medicine, 2017, 1: 69-77.

[4] Tang, Z., Li, C., Kang, B., Gao, G., Li, C., Zhang, Z., GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses, Nucleic Acids Res., 2017, 45: 98-102.

[5] An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients, Breast Cancer Res Treatment, 2010.

[6] Van, D.S., Vosa, U., Graaf, A., Franke, L., Magalhaes, J.P., Gene co-expression analysis for functional classification and gene-disease predictions, Brief Bioinform., 2018, 19: 575-592.

[7] Cui, L., Zhou, F., Chen, C., Wang, C.C., Overexpression of CCDC69 activates p14(ARF)/MDM2/p53 pathway and confers cisplatin sensitivity, J Ovarian Res., 2019, 12: 4.

[8] Clocchiatti, A., Ghosh, S., Procopio, M.G., Mazzeo, L., Bordignon, P., Ostano, P., Goruppi, S., Bottoni, G., Katarkar, A., Levesque, M., Kölblinger, P., Dummer, R., Neel, V., Özdemir, B.C., and Dotto, G.P., Androgen receptor functions as transcriptional repressor of cancer-associated fibroblast activation, J. Clin. Invest., 2018, 128: 5531-5548.

[9] Pal, D., Wu, D., Haruta, A., Matsumura, F., Wei, Q., Role of a novel coiled-coil domain-containing protein CCDC69 in regulating central spindle assembly, Cell Cycle., 2010, 9: 4117-4129.

[10] Fanale, D., Bronte, G., Passiglia, F., Calo, V., Castiglia, M., Piazza, D.F., Barraco, N., Cangemi, A., Catarella, M.T., Insalaco, L., Listì, A., Maragliano, R., Massihnia, D., Perez, A., Toia, F., Cicero, G., Bazan, V., Stabilizing versus destabilizing the microtubules: a double-edge sword for an effective cancer treatment option?, Anal. Cell. Pathol., 2015, 2015: 690916.

[11] Escuin, D., Kline, E.R., Giannakakou, P., Both microtubule-stabilizing and microtubule-destabilizing drugs inhibit hypoxia-inducible factor-1alpha accumulation and activity by disrupting microtubule function, Cancer. Res., 2005, 65: 9021-9028.


Refbacks

  • There are currently no refbacks.
Copyright © 2019 Animesh Chowdhury


Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.