Identification of AUNIP as a candidate diagnostic and prognostic biomarker for oral squamous cell carcinoma
Zongcheng Yang, Xiuming Liang, Yue Fu, Yingjiao Liu, Lixin Zheng, Fen Liu, Tongyu Li, Xiaolin Yin, Xu Qiao, Xin Xu, Zongcheng Yang, Xiuming Liang, Yue Fu, Yingjiao Liu, Lixin Zheng, Fen Liu, Tongyu Li, Xiaolin Yin, Xu Qiao, Xin Xu
Abstract
Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors worldwide. Patients with poorly differentiated OSCC often exhibit a poor prognosis. AUNIP (Aurora Kinase A and Ninein Interacting Protein), also known as AIBp, plays a key role in cell cycle and DNA damage repair. However, the function of AUNIP in OSCC remains elusive.
Methods: The differentially expressed genes (DEGs) were obtained using R language. Receiver operating characteristic curve analysis was performed to identify diagnostic markers for OSCC. The effectiveness of AUNIP in diagnosing OSCC was evaluated by machine learning. AUNIP expression was analyzed in publicly available databases and clinical specimens. Bioinformatics analysis and in vitro experiments were conducted to explore biological functions and prognostic value of AUNIP in OSCC.
Findings: The gene integration analysis revealed 90 upregulated DEGs. One candidate biomarker, AUNIP, for the diagnosis of OSCC was detected, and its expression gradually increased along with malignant differentiation of OSCC. Bioinformatics analysis demonstrated that AUNIP could be associated with tumor microenvironment, human papillomavirus infection, and cell cycle in OSCC. The suppression of AUNIP inhibited OSCC cell proliferation and resulted in G0/G1 phase arrest in OSCC cells. The survival analysis showed that AUNIP overexpression predicted poor prognosis of OSCC patients.
Interpretation: AUNIP could serve as a candidate diagnostic and prognostic biomarker for OSCC and suppression of AUNIP may be a potential approach to preventing and treating OSCC. FUND: Taishan Scholars Project in Shandong Province (ts201511106) and the National Natural Science Foundation of China (Nos. 61603218).
Keywords: AUNIP; Biomarker; Oral squamous cell carcinoma; Receiver operating characteristic curve; Survival analysis; Weighted gene co-expression network analysis.
Conflict of interest statement
The authors declare no conflicts of interest.
Copyright © 2019. Published by Elsevier B.V.
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References
- Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
- Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.
- Shi J., Bao X., Liu Z., Zhang Z., Chen W., Xu Q. Serum miR-626 and miR-5100 are promising prognosis predictors for Oral squamous cell carcinoma. Theranostics. 2019;9(4):920–931.
- Huang T.H., Li K.Y., Choi W.S. Lymph node ratio as prognostic variable in oral squamous cell carcinomas: systematic review and meta-analysis. Oral Oncol. 2019;89:133–143.
- Gharat S.A., Momin M., Bhavsar C. Oral squamous cell carcinoma: current treatment strategies and nanotechnology-based approaches for prevention and therapy. Crit Rev Ther Drug Carrier Syst. 2016;33(4):363–400.
- Zhao X., Sun S., Zeng X., Cui L. Expression profiles analysis identifies a novel three-mRNA signature to predict overall survival in oral squamous cell carcinoma. Am J Cancer Res. 2018;8(3):450–461.
- Yen C.J., Tsou H.H., Hsieh C.Y. Sequential therapy of neoadjuvant biochemotherapy with cetuximab, paclitaxel, and cisplatin followed by cetuximab-based concurrent bioradiotherapy in high-risk locally advanced oral squamous cell carcinoma: final analysis of a phase 2 clinical trial. Head Neck. 2019;41(6):1703–1712.
- Gan C.P., Sam K.K., Yee P.S. IFITM3 knockdown reduces the expression of CCND1 and CDK4 and suppresses the growth of oral squamous cell carcinoma cells. Cell Oncol (Dordr) 2019;42(4):477–490.
- Li J.M., Tseng C.W., Lin C.C. Upregulation of LGALS1 is associated with oral cancer metastasis. Ther Adv Med Oncol. 2018;10 1758835918794622.
- Hussein A.A., Forouzanfar T., Bloemena E. A review of the most promising biomarkers for early diagnosis and prognosis prediction of tongue squamous cell carcinoma. Br J Cancer. 2018;119(6):724–736.
- Rivera C., Oliveira A.K., Costa R.A.P., De Rossi T., Paes Leme A.F. Prognostic biomarkers in oral squamous cell carcinoma: a systematic review. Oral Oncol. 2017;72:38–47.
- Liu X., Wu J., Zhang D. Identification of potential key genes associated with the pathogenesis and prognosis of gastric cancer based on integrated bioinformatics analysis. Front Genet. 2018;9:265.
- Ni M., Liu X., Wu J. Identification of candidate biomarkers correlated with the pathogenesis and prognosis of non-small cell lung cancer via integrated bioinformatics analysis. Front Genet. 2018;9:469.
- Lieu A.S., Cheng T.S., Chou C.H. Functional characterization of AIBp, a novel Aurora-a binding protein in centrosome structure and spindle formation. Int J Oncol. 2010;37(2):429–436.
- Chou C.H., Loh J.K., Yang M.C. AIBp regulates mitotic entry and mitotic spindle assembly by controlling activation of both Aurora-A and Plk1. Cell Cycle. 2015;14(17):2764–2776.
- Lou J., Chen H., Han J. AUNIP/C1orf135 directs DNA double-strand breaks towards the homologous recombination repair pathway. Nat Commun. 2017;8(1):985.
- Foy J.P., Bertolus C., Ortiz-Cuaran S. Immunological and classical subtypes of oral premalignant lesions. Oncoimmunology. 2018;7(12)
- Wang Y., Fan H., Zheng L. Biological information analysis of differentially expressed genes in oral squamous cell carcinoma tissues in GEO database. J BUON. 2018;23(6):1662–1670.
- Wang R., Zhou X., Wang H. Integrative analysis of gene expression profiles reveals distinct molecular characteristics in oral tongue squamous cell carcinoma. Oncol Lett. 2019;17(2):2377–2387.
- Bai S., Zhang P., Zhang J.C. A gene signature associated with prognosis and immune processes in head and neck squamous cell carcinoma. Head Neck. 2019;41(8):2581–2590.
- Chabanais J., Labrousse F., Chaunavel A., Germot A., Maftah A. POFUT1 as a promising novel biomarker of colorectal cancer. Cancers (Basel) 2018;10(11)
- Yoshihara K., Shahmoradgoli M., Martinez E. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612.
- Hosmer D.W., Lemeshow S., Sturdivant R.X. 3rd ed. Wiley; Hoboken, New Jersey: 2013. Applied logistic regression.
- Müller A.C., Guido S. 1st ed. O'Reilly Media, Inc; Sebastopol, CA: 2016. Introduction to machine learning with Python: A guide for data scientists.
- Azim H.A., Jr., Peccatori F.A., Brohee S. RANK-ligand (RANKL) expression in young breast cancer patients and during pregnancy. Breast Cancer Res. 2015;17:24.
- Beckerman P., Qiu C., Park J. Human kidney tubule-specific gene expression based dissection of chronic kidney disease traits. EBioMedicine. 2017;24:267–276.
- Tang J., Kong D., Cui Q. Prognostic genes of breast cancer identified by gene co-expression network analysis. Front Oncol. 2018;8:374.
- Rosen E.Y., Wexler E.M., Versano R. Functional genomic analyses identify pathways dysregulated by progranulin deficiency, implicating Wnt signaling. Neuron. 2011;71(6):1030–1042.
- Carnielli C.M., Macedo C.C.S., De Rossi T. Combining discovery and targeted proteomics reveals a prognostic signature in oral cancer. Nat Commun. 2018;9(1):3598.
- Wang S., Yin S., Zhang Z.L., Su X., Xu Z.F. Quality of life after oral cancer resection and free flap reconstruction. J Oral Maxillofac Surg. 2019;77(8):1724–1732.
- Kansy K., Hoffmann J., Alhalabi O. Subjective and objective appearance of head and neck cancer patients following microsurgical reconstruction and associated quality of life horizontal line a cross-sectional study. J Craniomaxillofac Surg. 2018;46(8):1275–1284.
- Sequeira I., Neves J.F., Carrero D. Immunomodulatory role of keratin 76 in oral and gastric cancer. Nat Commun. 2018;9(1):3437.
- Wang Y., Guo W., Li Z. Role of the EZH2/miR-200 axis in STAT3-mediated OSCC invasion. Int J Oncol. 2018;52(4):1149–1164.
- Keshavarzi M., Darijani M., Momeni F. Molecular imaging and oral cancer diagnosis and therapy. J Cell Biochem. 2017;118(10):3055–3060.
- Baykul T., Yilmaz H.H., Aydin U., Aydin M.A., Aksoy M., Yildirim D. Early diagnosis of oral cancer. J Int Med Res. 2010;38(3):737–749.
- Murphy J., Isaiah A., Wolf J.S., Lubek J.E. Quality of life factors and survival after total or extended maxillectomy for sinonasal malignancies. J Oral Maxillofac Surg. 2015;73(4):759–763.
- Yang B., Chen Z., Huang Y., Han G., Li W. Identification of potential biomarkers and analysis of prognostic values in head and neck squamous cell carcinoma by bioinformatics analysis. Onco Targets Ther. 2017;10:2315–2321.
- Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674.
- Otto T., Sicinski P. Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer. 2017;17(2):93–115.
- Zhang P., Kawakami H., Liu W. Targeting CDK1 and MEK/ERK overcomes apoptotic resistance in BRAF-mutant human colorectal cancer. Mol Cancer Res. 2018;16(3):378–389.
- Peltanova B., Raudenska M., Masarik M. Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review. Mol Cancer. 2019;18(1):63.
- Huertas P., Cortes-Ledesma F., Sartori A.A., Aguilera A., Jackson S.P. CDK targets Sae2 to control DNA-end resection and homologous recombination. Nature. 2008;455(7213):689–692.
- Chapman J.R., Taylor M.R., Boulton S.J. Playing the end game: DNA double-strand break repair pathway choice. Mol Cell. 2012;47(4):497–510.
- Kanao R., Masutani C. Regulation of DNA damage tolerance in mammalian cells by post-translational modifications of PCNA. Mutat Res. 2017;803–805:82–88.
- Fakhry C., Blackford A.L., Neuner G. Association of oral human papillomavirus DNA persistence with cancer progression after primary treatment for oral cavity and oropharyngeal squamous cell carcinoma. JAMA Oncol. 2019;5(7):985–992.
- Slebos R.J., Yi Y., Ely K. Gene expression differences associated with human papillomavirus status in head and neck squamous cell carcinoma. Clin Cancer Res. 2006;12(3):701–709. Pt 1.
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