Anillin is a prognostic factor and is correlated with genovariation in pancreatic cancer based on databases analysis

Nie,Yuanhua; Zhao,Zhiqiang; Chen,Minxue; Ma,Fulin; Fan,Yong; Kang,Yingxin; Kang,Boxiong; Wang,Chen

doi:10.3892/ol.2020.12368

Anillin is a prognostic factor and is correlated with genovariation in pancreatic cancer based on databases analysis

Authors:
- Yuanhua Nie
- Zhiqiang Zhao
- Minxue Chen
- Fulin Ma
- Yong Fan
- Yingxin Kang
- Boxiong Kang
- Chen Wang
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Affiliations: Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730030, P.R. China
Published online on: December 10, 2020 https://doi.org/10.3892/ol.2020.12368
Article Number: 107
Copyright: © Nie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pancreatic cancer has a low survival rate globally. Anillin (ANLN) is involved in the pathogenesis of pancreatic cancer (PC). The present study used databases and reverse transcription‑quantitative PCR to investigate the association between ANLN expression, clinical variables and the survival rate of patients with pancreatic cancer. Gene expression of ANLN in normal and cancer tissues was analyzed using data from The Cancer Genome Atlas, Oncomine and Gene Expression database of Normal and Tumor tissues 2 and ANOVA, and the association between ANLN mRNA expression and ANLN genovariation was analyzed using cBioPortal. The association between ANLN expression and the survival, clinical, pathological and prognostic characteristics of PC was analyzed using Kaplan‑Meier (K‑M) survival analysis, Kruskal Wallis and Mann Whitney‑U tests, and logistic and Cox regression models. Gene Set Enrichment Analysis (GSEA) revealed the molecular pathways underpinning ANLN function in PC. Overexpression of ANLN was observed in PC cells (normal vs. tumor, P<0.01) and tissues (normal vs. tumor, P=0.008). Enhanced ANLN expression was associated with high tumor grade (grade 1 vs. grade 3, odds ratio: 5.662, P<0.001). However, ANLN expression was not associated with other clinical features (all P>0.05). K‑M analysis suggested that increased ANLN expression was associated with poor survival (P=0.002). Univariate and multivariate analysis revealed the ANLN is an independent prognostic factor for PC (P<0.001). GSEA demonstrated the p53, cell cycle, DNA replication, mismatch repair, nucleotide excision repair and PC pathways were associated with low expression of ANLN. Overall, ANLN is more highly expressed in PC compared with in normal tissue, and is associated with poor differentiation. The expression of ANLN may be a novel prognostic marker of poor survival. Finally, ANLN exert its functions in PC through the p53, cell cycle, DNA replication, mismatch repair and nucleotide excision repair and pathways.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	McGuigan A, Kelly P, Turkington RC, Jones C, Coleman HG and McCain RS: Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol. 24:4846–4861. 2018. View Article : Google Scholar : PubMed/NCBI
3	American Cancer Society, . Cancer Facts & Figures 2020. American Cancer Society, Inc.; Atlanta, GA: 2020, simplehttps://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2020.htmlFebruary. 2020
4	Mizrahi JD, Surana R, Valle JW and Shroff RT: Pancreatic cancer. Lancet. 395:2008–2020. 2020. View Article : Google Scholar : PubMed/NCBI
5	Avgerinos DV and Björnsson J: Malignant neoplasms: Discordance between clinical diagnoses and autopsy findings in 3,118 cases. Apmis. 109:774–780. 2010. View Article : Google Scholar
6	Bosetti C, Bertuccio P, Negri E, La Vecchia CL, Zeegers MP and Boffetta P: Pancreatic cancer: Overview of descriptive epidemiology. Mol Carcinog. 51:3–13. 2012. View Article : Google Scholar : PubMed/NCBI
7	Lambe M, Eloranta S, Wigertz A and Blomqvist P: Pancreatic cancer; reporting and long-term survival in Sweden. Acta Oncol. 50:1220–1227. 2011. View Article : Google Scholar : PubMed/NCBI
8	Oberstein PE and Olive KP: Pancreatic cancer: Why is it so hard to treat? Therap Adv Gastroenterol. 6:321–337. 2013. View Article : Google Scholar : PubMed/NCBI
9	Sens MA, Zhou XD, Weiland T and Cooley AM: Unexpected neoplasia in autopsies: Potential implications for tissue and organ safety. Arch Pathol Lab Med. 133:1923–1931. 2009.PubMed/NCBI
10	Uzunparmak B and Sahin IH: Pancreatic cancer microenvironment: A current dilemma. Clin Transl Med. 8:2019. View Article : Google Scholar : PubMed/NCBI
11	Field CM and Alberts BM: Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex. J Cell Biol. 131:165–178. 1995. View Article : Google Scholar : PubMed/NCBI
12	Oegema K, Savoian MS, Mitchison TJ and Field CM: Functional analysis of a human homologue of the drosophila actin binding protein anillin suggests a role in cytokinesis. J Cell Biol. 150:539–552. 2000. View Article : Google Scholar : PubMed/NCBI
13	Gould GW: Animal cell cytokinesis: The role of dynamic changes in the plasma membrane proteome and lipidome. Semin Cell Dev Biol. 53:64–73. 2016. View Article : Google Scholar : PubMed/NCBI
14	Goyal A, Takaine M, Simanis V and Nakano K: Dividing the spoils of growth and the cell cycle: The fission yeast as a model for the study of cytokinesis. Cytoskeleton (Hoboken). 68:69–88. 2011. View Article : Google Scholar : PubMed/NCBI
15	D'Avino PP: How to scaffold the contractile ring for a safe cytokinesis-lessons from Anillin-related proteins. J Cell Sci. 122:1071–1079. 2009. View Article : Google Scholar : PubMed/NCBI
16	Song K, Russo G and Krauss M: Septins as modulators of endo-lysosomal membrane traffic. Front Cell Dev Biol. 4:1242016. View Article : Google Scholar : PubMed/NCBI
17	Suzuki C, Daigo Y, Ishikawa N, Kato T, Hayama S, Ito T, Tsuchiya E and Nakamura Y: ANLN plays a critical role in human lung carcinogenesis through the activation of RHOA and by involvement in the phosphoinositide 3-kinase/AKT pathway. Cancer Res. 65:11314–11325. 2005. View Article : Google Scholar : PubMed/NCBI
18	Wang G, Shen W, Cui L, Chen W, Hu X and Fu J: Overexpression of Anillin (ANLN) is correlated with colorectal cancer progression and poor prognosis. Cancer Biomark. 16:459–465. 2016. View Article : Google Scholar : PubMed/NCBI
19	Zeng S, Yu X, Ma C, Song R, Zhang Z, Zi X, Chen X, Wang Y, Yu Y, Zhao J, et al: Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma. Sci Rep. 7:31512017. View Article : Google Scholar : PubMed/NCBI
20	Olakowski M, Tyszkiewicz T, Jarzab M, Król R, Oczko-Wojciechowska M, Kowalska M, Kowal M, Gala GM, Kajor M, Lange D, et al: NBL1 and anillin (ANLN) genes over-expression in pancreatic carcinoma. Folia Histochem Cytobiol. 47:249–255. 2009. View Article : Google Scholar : PubMed/NCBI
21	Wang Z, Chen J, Zhong MZ, Huang J, Hu YP, Feng DY, Zhou ZJ, Luo X, Liu ZQ, Jiang WZ and Zhou WB: Overexpression of ANLN contributed to poor prognosis of anthracycline-based chemotherapy in breast cancer patients. Cancer Chemother Pharmacol. 79:535–543. 2017. View Article : Google Scholar : PubMed/NCBI
22	Tamura K, Furihata M, Tsunoda T, Ashida S, Takata R, Obara W, Yoshioka H, Daigo Y, Nasu Y, Kumon H, et al: Molecular features of hormone-refractory prostate cancer cells by genome-wide gene expression profiles. Cancer Res. 67:5117–5125. 2007. View Article : Google Scholar : PubMed/NCBI
23	Park SJ, Yoon BH, Kim SK and Kim SY: GENT2: An updated gene expression database for normal and tumor tissues. BMC Med Genomics. 12 (Suppl 5):1012019. View Article : Google Scholar : PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
25	Team R: RStudio: Integrated Development for R, 2015. RStudio, Inc.; Boston, MA: 2015, simplehttp://www.rstudio.com PubMed/NCBI
26	Long X, Zhou W, Wang Y and Liu S: Prognostic significance of ANLN in lung adenocarcinoma. Oncol Lett. 16:1835–1840. 2018.PubMed/NCBI
27	Sadi AM, Wang DY, Youngson BJ, Miller N, Boerner S, Done SJ and Leong WL: Clinical relevance of DNA microarray analyses using archival formalin-fixed paraffin-embedded breast cancer specimens. Bmc Cancer. 11:2532011. View Article : Google Scholar : PubMed/NCBI
28	Wang S, Mo Y, Midorikawa K, Zhang Z, Huang G, Ma N, Zhao W, Hiraku Y, Oikawa S and Murata M: The potent tumor suppressor miR-497 inhibits cancer phenotypes in nasopharyngeal carcinoma by targeting ANLN and HSPA4L. Oncotarget. 6:35893–35907. 2015. View Article : Google Scholar : PubMed/NCBI
29	Weinberger P, Ponny SR, Xu H, Bai S, Smallridge R, Copland J and Sharma A: Cell Cycle M-Phase genes are highly upregulated in anaplastic thyroid carcinoma. Thyroid. 27:236–252. 2016. View Article : Google Scholar : PubMed/NCBI
30	Xia L, Su X, Shen J, Meng Q, Yan J, Zhang C, Chen Y, Wang H and Xu M: ANLN functions as a key candidate gene in cervical cancer as determined by integrated bioinformatic analysis. Cancer Manag Res. 10:663–670. 2018. View Article : Google Scholar : PubMed/NCBI
31	Wang A, Dai H, Gong Y, Zhang C, Shu J, Luo Y, Jiang Y, Liu W and Bie P: ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis. J Exp Clin Cancer Res. 38:3472019. View Article : Google Scholar : PubMed/NCBI
32	Zeng S: The mechanism of ANLN in the carcinogenesis of bladder cancer. PhD dissertationChinese People's Liberation Army Naval Medical University Shanghai 211 Engineering College, Shanghai, China2017.
33	Liu L, Wang J, Sun G, Wu Q, Ma J, Zhang X, Huang N, Bian Z, Gu S, Xu M, et al: m⁶A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma. Mol Cancer. 18:1882019. View Article : Google Scholar : PubMed/NCBI
34	Ghoshal K, Majumder S, Li Z, Dong X and Jacob ST: Suppression of metallothionein gene expression in a rat hepatoma because of promoter-specific DNA methylation. J Biol Chem. 275:539–547. 2000. View Article : Google Scholar : PubMed/NCBI
35	Nigg EA: Mitotic kinases as regulators of cell division and its checkpoints. 2:21–32. 2001.
36	Kiyomitsu T and Cheeseman IM: Cortical dynein and asymmetric membrane elongation coordinately position the spindle in anaphase. Cell. 154:391–402. 2013. View Article : Google Scholar : PubMed/NCBI
37	Brinkley BR: Managing the centrosome numbers game: From chaos to stability in cancer cell division. Trends Cell Biol. 11:18–21. 2001. View Article : Google Scholar : PubMed/NCBI