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Identification of a Novel Prognostic Signature for Breast Cancer Based on Post-translational Ubiquitin and Ubiquitin-Like Modification-Related Genes
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  • Nanyang Zhou,
  • Dejia Kong,
  • Qiao Lin,
  • Xiaojing Yang,
  • Dan Zhou,
  • Lihua Lou,
  • Xiangming Lou
Nanyang Zhou
Hangzhou Women's Hospital
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Dejia Kong
Hangzhou Women's Hospital
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Qiao Lin
Hangzhou Women's Hospital
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Xiaojing Yang
Hangzhou Women's Hospital
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Dan Zhou
Hangzhou Women's Hospital
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Lihua Lou
Hangzhou Women's Hospital
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Xiangming Lou
Hangzhou Women's Hospital

Corresponding Author:[email protected]

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Abstract

Background: Ubiquitin and ubiquitin-like (UUL) modifications play pleiotropic functions and are subject to fine regulatory mechanisms frequently altered in cancer. However, the comprehensive impact of UUL modification on breast cancer remains unclear. Methods: Transcriptomic and clinical data of breast cancer were downloaded from TCGA and GEO databases. Molecular subtyping of breast cancer was conducted using the NMF and CIBERSORT algorithms. Prognostic genes were identified via univariate, lasso and multivariate Cox regression analyses. Clinical pathological features, immune cell infiltration, immune therapeutic response and chemotherapy drug sensitivity were compared between groups using the Wilcoxon test. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Results: In breast cancer, 63 UUL modification-related genes were differentially expressed, with 29 up-regulated and 34 down-regulated genes. These genes were used to generate two UUL modification patterns that exhibited significant differences in prognostic features and immune cell infiltration. The UUL modification patterns were associated with 2038 differentially expressed genes that were significantly enriched in nuclear division, chromosome segregation, neuroactive ligand-receptor interaction, cell cycle, and other biological processes. Of these genes, 425 were associated with breast cancer prognosis, which enabled the classification of breast cancer into two clusters with significantly distinct prognoses. We developed a prognostic model, UULscore, which comprised nine genes and showed a significant correlation with partial immune cell infiltration. Furthermore, UULscore demonstrated potential predictive value in breast cancer overall survival prediction, immune therapeutic response, and chemotherapy drug sensitivity. UULscore, stage, radiotherapy, and chemotherapy were identified as independent prognostic factors for breast cancer. Based on these factors, a nomogram model was constructed, which demonstrated exceptional prognostic predictive performance. Conclusion: In conclusion, we identified two UUL modification-derived molecular subtypes in breast cancer, and have successfully constructed a risk scoring model that holds potential value in prognosis, immune infiltration, immune therapeutic response, and chemotherapy sensitivity.
11 Sep 2023Submitted to Cancer Reports
12 Sep 2023Submission Checks Completed
12 Sep 2023Assigned to Editor
12 Sep 2023Review(s) Completed, Editorial Evaluation Pending
16 Sep 2023Reviewer(s) Assigned
09 Nov 2023Editorial Decision: Revise Major