Integrated analysis reveals prognostic value and progression-related role of AMIGO2 in prostate cancer

Zhaodong Han; Yuanfa Feng; Yulin Deng; Zhenfeng Tang; Shanghua Cai; Yangjia Zhuo; Yingke Liang; Jianheng Ye; Zhouda Cai; Shuai Yang; Yuxiang Liang; Chi Tin Hon; Jiahong Chen; Weide Zhong

doi:10.21037/tau-21-1148

Integrated analysis reveals prognostic value and progression-related role of AMIGO2 in prostate cancer

Transl Androl Urol. 2022 Jul;11(7):914-928. doi: 10.21037/tau-21-1148.

Authors

Zhaodong Han^#¹, Yuanfa Feng^#^{1

2}, Yulin Deng^#^{1

2}, Zhenfeng Tang^{1

2}, Shanghua Cai², Yangjia Zhuo¹, Yingke Liang¹, Jianheng Ye¹, Zhouda Cai¹, Shuai Yang³, Yuxiang Liang¹, Chi Tin Hon⁴, Jiahong Chen⁵, Weide Zhong^{1

2

4}

Affiliations

¹ Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
² Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
³ Department of Urology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
⁴ Macau Institute of Systems Engineering, Macau University of Science and Technology, Avenida Wai Long, Macau, China.
⁵ Department of Urology, Huizhou Municipal Central Hospital, Huizhou, China.

^# Contributed equally.

Abstract

Background: Even though emerging studies supplied evidence that Adhesion Molecule with Ig Like Domain family 2 (AMIGO2) plays a critical role in numerous cancers, comprehensive analysis of the prognostic value and significant role of AMIGO2 in prostate cancer (PCa) have not been described.

Methods: Differentially expressed analysis, survival analysis and univariate cox regression analysis were first performed to explore the diagnostic and prognostic role of AMIGO2 in various cancers, especially in PCa. Tissue microarray were used to examined the association between AMGIO2 and clinical features. Multivariate cox regression analysis, concordance index, nomogram construction, the receiver operator characteristic curve and calibration curves were further used to discover the effects of AMIGO2 on recurrence-free survival (RFS) and clinicopathological characteristics, including age, Gleason score (GS) and tumor stage. Genetic and Epigenetic Alterations analysis were further conducted to explore the potential effect of AMIGO2 in PCa and examined by biological function analysis and in vitro experiments.

Results: AMIGO2 was associated with poor RFS (P<0.05) and differentially expressed (P<0.05) in multiple cancer type, especially in PCa. Besides, decreasing the expression of AMIGO2 inhibited PCa cell proliferation and colony formation in vitro. In addition, AMIGO2 was a reliable prognostic marker providing additional information (C-index: 0.7) that supplement the currently used prognosis evaluation system, e.g., T stage (C-index: 0.62) and GS (C-index: 0.65). A novel nomogram was established based on AMIGO2, tumor stage and GS with accuracies (areas under curve) of 0.70, 0.78 and 0.82 for predicting 3-, 5- and 7-year RFS, respectively. Bioinformatic analysis and in vitro examination also suggested that AMIGO2 might involve in the progression of PCa tumors inducing epithelial mesenchymal transition (EMT).

Conclusions: We identified AMIGO2 as a pan-cancer gene that could not only be a prognostic biomarker in various cancers, especially in PCa, but may functionally promoting PCa progression via EMT and mediating docetaxel resistance, suggesting AMIGO2 as a potential target for future treatment of PCa.

Keywords: AMIGO2; Prostate cancer (PCa); prognosis; progression; recurrence-free survival (RFS).