Ubiquitin-related lncRNAs: The new tool for prognosis prediction in prostate cancer

Xiang Liu; Wangli Mei; Liang Jin; Xianchao Sun; Zhen Zhou; Shiyong Xin; Liqun Huang; Guosheng Yang; Jinyou Wang; Lin Ye

doi:10.3389/fonc.2022.948113

Ubiquitin-related lncRNAs: The new tool for prognosis prediction in prostate cancer

Front Oncol. 2022 Sep 13:12:948113. doi: 10.3389/fonc.2022.948113. eCollection 2022.

Authors

Xiang Liu^{1

2}, Wangli Mei^{2

3}, Liang Jin^{2

3}, Xianchao Sun², Zhen Zhou¹, Shiyong Xin², Liqun Huang², Guosheng Yang², Jinyou Wang⁴, Lin Ye²

Affiliations

¹ Department of Urology, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai, China.
² Department of Urology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
³ Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
⁴ Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Abstract

Objective: To establish a ubiquitin-related long noncoding ribonucleic acids (lncRNAs) prognosis prediction model for prostate cancer (Pca).

Methods: Data were acquired through The Cancer Genome Atlas (TCGA) database. Ubiquitin-related differentially expressed genes (DEGs) and lncRNAs in Pca were filtered out. UBE2S was selected as the representative gene and validated in vitro. Progression-free survival (PFS) predictive signature was established with ubiquitin-related lncRNAs screened by Cox regression analyses and internally validated. A nomogram was constructed to assess the prognosis of Pca patients. Gene enrichment analysis was performed to explore functional differences based on risk stratification. Between different risk groups, immune status and drug sensitivity were contrasted.

Results: A total of 254 ubiquitin-related genes were screened. UBE2S was shown to promote the proliferation of Pca cells in vitro. The predictive signature was established based on six ubiquitin-related lncRNAs and validated. The prognosis of Pca patients was worse with an increasing risk score. The area under the curve (AUC) of the signature was higher than that of clinicopathological variables (0.806 vs 0.504-0.701). The AUC was 0.811 for 1-year PFS, 0.807 for 3-year PFS, and 0.790 for 5-year PFS. The calibration curves of risk score-based nomogram demonstrated high consistency. By contrasting the expression of immune function, cells, and checkpoints, we found that the signature was closely related to immunity. The high-risk patients were more sensitive to gemcitabine, cisplatin, bortezomib, etc. and resistant to bicalutamide.

Conclusion: The ubiquitin-related lncRNAs can effectively predict the prognosis of Pca and may provide new treatment options for Pca.

Keywords: lncRNA; prognosis; progression-free survival; prostate cancer; ubiquitin.