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Cancer Cell International

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Open Access 01-12-2022 | Gastric Cancer | Research

Comprehensive analyses reveal the carcinogenic and immunological roles of ANLN in human cancers

Authors: Yanlong Shi, Xinyu Ma, Menglu Wang, Sheng Lan, Haokun Jian, Yue Wang, Qian Wei, Fei Zhong

Published in: Cancer Cell International | Issue 1/2022

Abstract

Background

Anillin (ANLN) is an actin-binding protein that is essential for cell division and contributes to cell growth and migration. Although previous studies have shown that ANLN is related to carcinogenesis, no pan-cancer analyses of ANLN have been reported. Accordingly, in this study, we evaluated the carcinogenic roles of ANLN in various cancer types using online databases.

Methods

We evaluated the potential carcinogenic roles of ANLN using TIMER2 and Gene Expression Omnibus databases with 33 types of cancers. We further investigated the associations of ANLN with patient prognosis, genetic alterations, phosphorylation levels, and immune infiltration in multiple cancers using GEPIA2, cBioPortal, UACLAN, and TIMER2 databases. Additionally, the potential functions of ANLN were explored using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Reverse transcription quantitative polymerase chain reaction and immunohistochemistry were used to determine ANLN mRNA and protein expression in colorectal cancer (CRC), gastric cancer (GC), and hepatocellular carcinoma (HCC) cell lines.

Results

ANLN was overexpressed in various tumor tissues compared with corresponding normal tissues, and significant correlations between ANLN expression and patient prognosis, genetic alterations, phosphorylation levels, and immune infiltration were noted. Moreover, enrichment analysis suggested that ANLN functionally affected endocytosis, regulation of actin cytoskeleton, and oxytocin signaling pathways. Importantly, ANLN mRNA and protein expression levels were upregulated in gastrointestinal cancers, including CRC, GC, and HCC.

Conclusions

Our findings suggested that ANLN participated in tumorigenesis and cancer progression and may have applications as a promising biomarker of immune infiltration and prognosis in various cancers.

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Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. Ca-Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660.CrossRefPubMed

Torti D, Trusolino L. Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils. EMBO Mol Med. 2011;3(11):623–36. https://doi.org/10.1002/emmm.201100176.CrossRefPubMedPubMedCentral

Cui X, Zhang X, Liu M, Zhao C, Zhang N, Ren Y, Su C, Zhang W, Sun X, He J, et al. A pan-cancer analysis of the oncogenic role of staphylococcal nuclease domain-containing protein 1 (SND1) in human tumors. Genomics. 2020;112(6):3958–67. https://doi.org/10.1016/j.ygeno.2020.06.044.CrossRefPubMed

Ye W, Luo C, Liu F, Liu Z, Chen F. CD96 Correlates with Immune Infiltration and Impacts Patient Prognosis: A Pan-Cancer Analysis. Front Radiat Oncol. 2021;11:634617. https://doi.org/10.3389/fonc.2021.634617.CrossRef

Blum A, Wang P. Zenklusen JC: SnapShot: TCGA-Analyzed Tumors. Cell. 2018;173(2):530. https://doi.org/10.1016/j.cell.2018.03.059.CrossRefPubMed

Sang C, Chao C, Wang M, Zhang Y, Luo G, Zhang X. Identification and validation of hub microRNAs dysregulated in esophageal squamous cell carcinoma. Aging. 2020;12(10):9807–24. https://doi.org/10.18632/aging.103245.CrossRefPubMedPubMedCentral

Hall G, Lane BM, Khan K, Pediaditakis I, Xiao J, Wu G, Wang L, Kovalik ME, Chryst-Stangl M, Davis EE, et al. The Human FSGS-Causing ANLN R431C Mutation Induces Dysregulated PI3K/AKT/mTOR/Rac1 Signaling in Podocytes. J Am Soc Nephrol. 2018;29(8):2110–22. https://doi.org/10.1681/asn.2017121338.CrossRefPubMedPubMedCentral

Oegema K, Savoian MS, Mitchison TJ, Field CM. Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis. J Cell Biol. 2000;150(3):539–52. https://doi.org/10.1083/jcb.150.3.539.CrossRefPubMedPubMedCentral

Wang Z, Chen J, Zhong MZ, Huang J, Hu YP, Feng DY, Zhou ZJ, Luo X, Liu ZQ, Jiang WZ, et al. Overexpression of ANLN contributed to poor prognosis of anthracycline-based chemotherapy in breast cancer patients. Cancer Chemother Pharmacol. 2017;79(3):535–43. https://doi.org/10.1007/s00280-017-3248-2.CrossRefPubMed

10.

Wang A, Dai H, Gong Y, Zhang C, Shu J, Luo Y, Jiang Y, Liu W, Bie P. ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis. J Exp Clin Cancer Res. 2019;38(1):347. https://doi.org/10.1186/s13046-019-1340-7.CrossRefPubMedPubMedCentral

11.

Skrzypski M, Jassem E, Taron M, Sanchez JJ, Mendez P, Rzyman W, Gulida G, Raz D, Jablons D, Provencio M, et al. Three-gene expression signature predicts survival in early-stage squamous cell carcinoma of the lung. Clin Cancer Res. 2008;14(15):4794–9. https://doi.org/10.1158/1078-0432.Ccr-08-0576.CrossRefPubMed

12.

Jia H, Gao Z, Yu F, Guo H, Li B. Actin-binding protein anillin promotes the progression of hepatocellular carcinoma in vitro and in mice. Exp Ther Med. 2021;21(5):454. https://doi.org/10.3892/etm.2021.9885.CrossRefPubMedPubMedCentral

13.

Uhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, Benfeitas R, Arif M, Liu Z, Edfors F, et al. A pathology atlas of the human cancer transcriptome. Science. 2017;357:6352. https://doi.org/10.1126/science.aan2507.CrossRef

14.

Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, Li B, Liu XS. TIMER20 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020;48(1):W509–14. https://doi.org/10.1093/nar/gkaa407.CrossRefPubMedPubMedCentral

15.

Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47(W1):W556–60. https://doi.org/10.1093/nar/gkz430.CrossRefPubMedPubMedCentral

16.

Chen F, Chandrashekar DS, Varambally S, Creighton CJ. Pan-cancer molecular subtypes revealed by mass-spectrometry-based proteomic characterization of more than 500 human cancers. Nat Commun. 2019;10(1):5679. https://doi.org/10.1038/s41467-019-13528-0.CrossRefPubMedPubMedCentral

17.

Barakat A, Mittal A, Ricketts D, Rogers BA. Understanding survival analysis: actuarial life tables and the Kaplan-Meier plot. Br J Hosp Med. 2019;80(11):642–6. https://doi.org/10.12968/hmed.2019.80.11.642.CrossRef

18.

Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signaling. 2013;6(269):1. https://doi.org/10.1126/scisignal.2004088.CrossRef

19.

Bardou P, Mariette J, Escudié F, Djemiel C, Klopp C. jvenn: an interactive Venn diagram viewer. BMC Bioinf. 2014;15(1):293. https://doi.org/10.1186/1471-2105-15-293.CrossRef

20.

Chen RQ, Yang QK, Lu BW, Yi W, Cantin G, Chen YL, Fearns C, Yates JR 3rd, Lee JD. CDC25B mediates rapamycin-induced oncogenic responses in cancer cells. Cancer Res. 2009;69(6):2663–8. https://doi.org/10.1158/0008-5472.Can-08-3222.CrossRefPubMedPubMedCentral

21.

Lowery DM, Clauser KR, Hjerrild M, Lim D, Alexander J, Kishi K, Ong SE, Gammeltoft S, Carr SA, Yaffe MB. Proteomic screen defines the Polo-box domain interactome and identifies Rock2 as a Plk1 substrate. EMBO J. 2007;26(9):2262–73. https://doi.org/10.1038/sj.emboj.7601683.CrossRefPubMedPubMedCentral

22.

Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP. Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A. 2004;101(33):12130–5. https://doi.org/10.1073/pnas.0404720101.CrossRefPubMedPubMedCentral

23.

Dephoure N, Zhou C, Villén J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP. A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008;105(31):10762–7. https://doi.org/10.1073/pnas.0805139105.CrossRefPubMedPubMedCentral

24.

Domingues P, González-Tablas M, Otero Á, Pascual D, Miranda D, Ruiz L, Sousa P, Ciudad J, Gonçalves JM, Lopes MC, et al. Tumor infiltrating immune cells in gliomas and meningiomas. Brain Behav Immun. 2016;53:1–15. https://doi.org/10.1016/j.bbi.2015.07.019.CrossRefPubMed

25.

Steven A, Seliger B. The Role of Immune Escape and Immune Cell Infiltration in Breast Cancer. Breast Care. 2018;13(1):16–21. https://doi.org/10.1159/000486585.CrossRefPubMedPubMedCentral

26.

Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discovery. 2019;18(2):99–115. https://doi.org/10.1038/s41573-018-0004-1.CrossRefPubMed

27.

Piekny AJ, Maddox AS. The myriad roles of Anillin during cytokinesis. Cell Dev Biol. 2010;21(9):881–91. https://doi.org/10.1016/j.semcdb.2010.08.002.CrossRef

28.

Tuan NM, Lee CH. Role of anillin in tumour: from a prognostic biomarker to a novel target. Cancers. 2020;12(6):1600. https://doi.org/10.3390/cancers12061600.CrossRefPubMedCentral

29.

Zhou W, Wang Z, Shen N, Pi W, Jiang W, Huang J, Hu Y, Li X, Sun L. Knockdown of ANLN by lentivirus inhibits cell growth and migration in human breast cancer. Mol Cell Biochem. 2015;398(1–2):11–9. https://doi.org/10.1007/s11010-014-2200-6.CrossRefPubMed

30.

Pandi NS, Manimuthu M, Harunipriya P, Murugesan M, Asha GV, Rajendran S. In silico analysis of expression pattern of a Wnt/β-catenin responsive gene ANLN in gastric cancer. Gene. 2014;545(1):23–9. https://doi.org/10.1016/j.gene.2014.05.013.CrossRefPubMed

31.

Bailey MH, Tokheim C, Porta-Pardo E, Sengupta S, Bertrand D, Weerasinghe A, Colaprico A, Wendl MC, Kim J, Reardon B, et al. Comprehensive characterization of cancer driver genes and mutations. Cell. 2018;173(2):371-385.e318. https://doi.org/10.1016/j.cell.2018.02.060.CrossRefPubMedPubMedCentral

32.

Yang D, Khan S, Sun Y, Hess K, Shmulevich I, Sood AK, Zhang W. Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA. 2011;306(14):1557–65. https://doi.org/10.1001/jama.2011.1456.CrossRefPubMedPubMedCentral

33.

Cha S, Lee E, Won HH. Comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites. NPJ breast cancer. 2021;7(1):93. https://doi.org/10.1038/s41523-021-00303-y.CrossRefPubMedPubMedCentral

34.

Angelova M, Charoentong P, Hackl H, Fischer ML, Snajder R, Krogsdam AM, Waldner MJ, Bindea G, Mlecnik B, Galon J, et al. Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy. Genome Biol. 2015;16(1):64. https://doi.org/10.1186/s13059-015-0620-6.CrossRefPubMedPubMedCentral

35.

Ju Q, Li X, Zhang H, Yan S, Li Y, Zhao Y. NFE2L2 Is a potential prognostic biomarker and is correlated with immune infiltration in brain lower grade glioma: a pan-cancer analysis. Oxid Med Cell Longevity. 2020;2020:3580719. https://doi.org/10.1155/2020/3580719.CrossRef

36.

Peranzoni E, Lemoine J, Vimeux L, Feuillet V, Barrin S, Kantari-Mimoun C, Bercovici N, Guérin M, Biton J, Ouakrim H, et al. Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti-PD-1 treatment. Proc Natl Acad Sci U S A. 2018;115(17):E4041–50. https://doi.org/10.1073/pnas.1720948115.CrossRefPubMedPubMedCentral

37.

Anker JF, Naseem AF, Mok H, Schaeffer AJ, Abdulkadir SA, Thumbikat P. Multi-faceted immunomodulatory and tissue-tropic clinical bacterial isolate potentiates prostate cancer immunotherapy. Nat Commun. 2018;9(1):1591. https://doi.org/10.1038/s41467-018-03900-x.CrossRefPubMedPubMedCentral

38.

Fiori ME, Di Franco S, Villanova L, Bianca P, Stassi G, De Maria R. Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance. Mol Cancer. 2019;18(1):70. https://doi.org/10.1186/s12943-019-0994-2.CrossRefPubMedPubMedCentral

39.

Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M, Sevillano M, Palomo-Ponce S, Tauriello DV, Byrom D, et al. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 2015;47(4):320–9. https://doi.org/10.1038/ng.3225.CrossRefPubMed

40.

Watkins LR, Orlandi C. Orphan G Protein Coupled Receptors in Affective Disorders. Genes. 2020;11:6. https://doi.org/10.3390/genes11060694.CrossRef

41.

Schnaar RL, Lopez PH. Myelin-associated glycoprotein and its axonal receptors. J Neurosci Res. 2009;87(15):3267–76. https://doi.org/10.1002/jnr.21992.CrossRefPubMedPubMedCentral

42.

Cloake NC, Yan J, Aminian A, Pender MP, Greer JM. PLP1 Mutations in Patients with Multiple Sclerosis: Identification of a New Mutation and Potential Pathogenicity of the Mutations. J Neurosci Res. 2018;7:10. https://doi.org/10.3390/jcm7100342.CrossRef

43.

Yang XM, Cao XY, He P, Li J, Feng MX, Zhang YL, Zhang XL, Wang YH, Yang Q, Zhu L, et al. Overexpression of Rac GTPase Activating Protein 1 contributes to proliferation of cancer cells by reducing hippo signaling to promote cytokinesis. Gastroenterology. 2018;155(4):1233-1249.e1222. https://doi.org/10.1053/j.gastro.2018.07.010.CrossRefPubMed

44.

Imaoka H, Toiyama Y, Saigusa S, Kawamura M, Kawamoto A, Okugawa Y, Hiro J, Tanaka K, Inoue Y, Mohri Y, et al. RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer. Carcinogenesis. 2015;36(3):346–54. https://doi.org/10.1093/carcin/bgu327.CrossRefPubMed

45.

Kamijo K, Ohara N, Abe M, Uchimura T, Hosoya H, Lee JS, Miki T. Dissecting the role of Rho-mediated signaling in contractile ring formation. Mol Biol Cell. 2006;17(1):43–55. https://doi.org/10.1091/mbc.e05-06-0569.CrossRefPubMedPubMedCentral

46.

Nishimura Y, Yonemura S. Centralspindlin regulates ECT2 and RhoA accumulation at the equatorial cortex during cytokinesis. J Cell Sci. 2006;119(Pt 1):104–14. https://doi.org/10.1242/jcs.02737.CrossRefPubMed

Title: Comprehensive analyses reveal the carcinogenic and immunological roles of ANLN in human cancers
Authors: Yanlong Shi
Xinyu Ma
Menglu Wang
Sheng Lan
Haokun Jian
Yue Wang
Qian Wei
Fei Zhong
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Gastric Cancer
Hepatocellular Carcinoma
Gastric Cancer
Hepatocellular Carcinoma
Biomarkers
Colorectal Cancer
Colorectal Cancer
Published in: Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-022-02610-1

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Abstract

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