Anillin actin-binding protein expression correlates with poor prognosis for prostate cancer patients

doi:10.1016/j.ajur.2023.07.002

Asian Journal of Urology, 2024, 11 (4): 569-574 doi: 10.1016/j.ajur.2023.07.002

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Anillin actin-binding protein expression correlates with poor prognosis for prostate cancer patients

Shinichiro Yamamoto^a,b,Daisuke Obinata^b,Kenichi Takayama^a,Daigo Funakoshi^b,Kyoko Fujiwara^c,Makoto Hara^d,Satoru Takahashi^b,Satoshi Inoue^a,e,*(

)

^aDepartment of Systems Aging Science and Medicine, Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, Japan
^bDepartment of Urology, Nihon University School of Medicine, 30-1, Ooyaguchikamicho, Itabashi-ku, Tokyo, Japan
^cDepartment of Anatomy, Nihon University School of Dentistry, 1-8-13, Kanda Surugadai, Chiyoda-ku, Tokyo, Japan
^dDivision of Neurology, Department of Medicine, Nihon University School of Medicine, 30-1, Ooyaguchikamicho, Itabashi-ku, Tokyo, Japan
^eResearch Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama, Japan

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Abstract

Objective: Octamer transcription factor 1 (OCT1), a transcription factor that interacts with androgen receptor, is involved in prostate cancer (PCa) progression. The OCT1 target gene, Anillin actin-binding protein (ANLN), is highly expressed in castration-resistant PCa tissue; however, it remains unclear whether ANLN expression in hormone-sensitive PCa tissue could be used as a predictive biomarker for poor prognosis of patients. We aimed to investigate ANLN expression in PCa tissue obtained via radical prostatectomy and its correlation with clinical parameters.

Methods: Immunohistochemical staining for ANLN was performed on 86 PCa specimens, followed by evaluation using immunoreactivity (IR) scores. Prognosis was analyzed by the log-rank test using the Kaplan-Meier method to generate a cancer-specific survival curve. The correlations between ANLN IR and clinical parameters as well as OCT1 IR were analyzed using the Chi-squared test.

Results: The median IR score was 0 for ANLN. Accordingly, given the low median IR score, an IR score of ≥3 was defined as positive. There were 17 (19.8%) ANLN-positive cases, and these cases had a significantly poorer prognosis. Multivariate analysis revealed that the Gleason score, pathological tumor and lymph node stages, and positive ANLN expression were significant predictors of poor prognosis. Notably, patients with both positive ANLN and high OCT1 expression had a significantly decreased overall survival (p=0.001).

Conclusion: ANLN, which is a OCT1 target gene especially in castration-resistant PCa, is expressed in a small number of hormone-sensitive PCa cases. Both positive ANLN expression and high OCT1 expression are significantly correlated with poor prognosis for PCa patients.

Key words： Prostate cancer Androgen receptor Octamer transcription factor 1 Anillin actin-binding protein

Received: 16 February 2023 Available online: 20 October 2024

Corresponding Authors: * Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute for Geriatrics and Gerontology,35-2 Sakae-cho, Itabashi-ku, Tokyo, Japan.E-mail address: sinoue@tmig.or.jp (S. Inoue).

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	Shinichiro Yamamoto
	Daisuke Obinata
	Kenichi Takayama
	Daigo Funakoshi
	Kyoko Fujiwara
	Makoto Hara
	Satoru Takahashi
	Satoshi Inoue

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Cite this article:

Shinichiro Yamamoto,Daisuke Obinata,Kenichi Takayama, et al. Anillin actin-binding protein expression correlates with poor prognosis for prostate cancer patients[J]. Asian Journal of Urology, 2024, 11(4): 569-574.

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http://www.ajurology.com/EN/10.1016/j.ajur.2023.07.002 OR http://www.ajurology.com/EN/Y2024/V11/I4/569

Representative immunohistochemical staining images. (A) Negative immunoreactivity in cancerous region; (B) Positive immunoreactivity in cancerous region; (C) Negative immunoreactivity in non-cancerous region. The scale bar indicates 25 μm.

Distribution of IR scores for ANLN antibody. ANLN expression was negative in 80% of the localized prostate cancer cases (52 cases with an IR score of 0 and 17 cases with an IR score of 2), while 17 cases have positive ANLN expression with an IR score of 3 or higher. IR, immunoreactivity; ANLN, Anillin actin-binding protein. Note:th-re were no cases with an IR score of 1.

Correlation between ANLN expression and clinicopathological findings in patients with prostate cancer (n=86).

Univariate and multivariate Cox proportional hazard analyses of overall survival (n=86).

The Kaplan-Meier cancer-specific survival curves for predicting prognosis of the 86 localized PCa cases. (A) According to ANLN expression. (B) According to both ANLN and OCT1 expression. ANLN, Anillin actin-binding protein; IR, immunoreactivity; OCT1, octamer transcription factor 1. IR scores were obtained as the sum of the proportion (0, none; 1, <1%; 2, 1%-10%; 3, 11%-33%; 4, 34%-66%, and 5, ≥67%) and the intensity (0, none; 1, weak; 2, moderate; and 3, strong) of IR; IR scores of ≥3 and ≥7 were defined as positive ANLN and high OCT1 expression, respectively [4,6].

[1]	Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med 2004; 10:33-9. doi: 10.1038/nm972 pmid: 14702632
[2]	Takayama K, Inoue S. Transcriptional network of androgen receptor in prostate cancer progression. Int J Urol 2013; 20:756-68.
[3]	Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 2008; 26:1148-59.
[4]	Obinata D, Takayama K, Urano T, Murata T, Kumagai J, Fujimura T, et al. Oct1 regulates cell growth of LNCaP cells and is a prognostic factor for prostate cancer. Int J Cancer 2012; 130:1021-8. doi: 10.1002/ijc.26043 pmid: 21387309
[5]	Takayama KI, Suzuki Y, Yamamoto S, Obinata D, Takahashi S, Inoue S. Integrative genomic analysis of OCT1 reveals coordinated regulation of androgen receptor in advanced prostate cancer. Endocrinology 2019; 160:463-72.
[6]	Obinata D, Takada S, Takayama K, Urano T, Ito A, Ashikari D, et al. Abhydrolase domain containing 2, an androgen target gene, promotes prostate cancer cell proliferation and migration. Eur J Cancer 2016; 57:39-49. doi: 10.1016/j.ejca.2016.01.002 pmid: 26854828
[7]	Yamamoto S, Takayama KI, Obinata D, Fujiwara K, Ashikari D, Takahashi S, et al. Identification of new octamer transcription factor 1-target genes upregulated in castration-resistant prostate cancer. Cancer Sci 2019; 110:3476-85.
[8]	Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007; 39:175-91. doi: 10.3758/bf03193146 pmid: 17695343
[9]	Obinata D, Takayama K, Takahashi S, Inoue S. Crosstalk of the androgen receptor with transcriptional collaborators: potential therapeutic targets for castration-resistant prostate cancer. Cancers 2017; 9:22. https://doi.org/10.3390/cancers9030022.
[10]	Sharma NL, Massie CE, Ramos-Montoya A, Zecchini V, Scott HE, Lamb AD, et al. The androgen receptor induces a distinct transcriptional program in castration-resistant prostate cancer in man. Cancer Cell 2013; 23:35-47. doi: 10.1016/j.ccr.2012.11.010 pmid: 23260764
[11]	Obinata D, Funakoshi D, Takayama K, Hara M, Niranjan B, Teng L, et al. OCT1-target neural gene PFN2 promotes tumor growth in androgen receptor-negative prostate cancer. Sci Rep 2022; 12:6094. https://doi.org/10.1038/s41598-022-10099-x. doi: 10.1038/s41598-022-10099-x pmid: 35413990
[12]	Migita T, Takayama KI, Urano T, Obinata D, Ikeda K, Soga T, et al. ACSL3 promotes intratumoral steroidogenesis in prostate cancer cells. Cancer Sci 2017; 108:2011-21.
[13]	Obinata D, Takayama K, Fujiwara K, Suzuki T, Tsutsumi S, Fukuda N, et al. Targeting Oct1 genomic function inhibits androgen receptor signaling and castration-resistant prostate cancer growth. Oncogene 2016; 35:6350-8. doi: 10.1038/onc.2016.171 pmid: 27270436
[14]	Bakht MK, Yamada Y, Ku SY, Venkadakrishnan VB, Korsen JA, Kalidindi TM, et al. Landscape of prostate-specific membrane antigen heterogeneity and regulation in AR-positive and ARnegativemetastaticprostatecancer. NatCancer 2023; 4:699-715.