Identification of a Prognostic Signature for Ovarian Cancer Based on Ubiquitin-Related Genes Suggesting a Potential Role for FBXO9

Xiaomei Luo; Yingjie Wang; Hao Zhang; Guangquan Chen; Jindan Sheng; Xiu Tian; Renhao Xue; Yu Wang

doi:10.3390/biom13121724

Biomolecules (Nov 2023)

Identification of a Prognostic Signature for Ovarian Cancer Based on Ubiquitin-Related Genes Suggesting a Potential Role for FBXO9

Xiaomei Luo,
Yingjie Wang,
Hao Zhang,
Guangquan Chen,
Jindan Sheng,
Xiu Tian,
Renhao Xue,
Yu Wang

Affiliations

Xiaomei Luo: Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China
Yingjie Wang: Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China
Hao Zhang: Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China
Guangquan Chen: Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China
Jindan Sheng: Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China
Xiu Tian: Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China
Renhao Xue: Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China
Yu Wang: Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China

DOI: https://doi.org/10.3390/biom13121724
Journal volume & issue: Vol. 13, no. 12
p. 1724

Abstract

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Background: Ovarian cancer (OV) is associated with high mortality and poses challenges in diagnosis and prognosis prediction. Ubiquitin-related genes (UbRGs) are involved in the initiation and progression of cancers, but have still not been utilized for diagnosis and prognosis of OV. Methods: K48-linked ubiquitination in ovarian tissues from our OV and control cohort was assessed using immunohistochemistry. UbRGs, including ubiquitin and ubiquitin-like regulators, were screened based on the TCGA-OV and GTEx database. Univariate Cox regression analysis identified survival-associated UbRGs. A risk model was established using the LASSO regression and multivariate Cox regression analysis. The relationship between UbRGs and immune cell infiltration, tumor mutational burden, drug sensitivity, and immune checkpoint was determined using the CIBERSORT, ESTIMATE, and Maftools algorithms, based on the Genomics of Drug Sensitivity in Cancer and TCGA-OV databases. GEPIA2.0 was used to analyze the correlation between FBXO9/UBD and DNA damage repair-related genes. Finally, FBXO9 and UBD were accessed in tissues or cells using immunohistochemistry, qPCR, and Western blot. Results: We confirmed the crucial role for ubiquitination in OV as a significant decrease of K48-linked ubiquitination was observed in primary OV lesions. We identified a prognostic signature utilizing two specific UbRGs, FBXO9 and UBD. The risk score obtained from this signature accurately predicted the overall survival of TCGA-OV training dataset and GSE32062 validation dataset. Furthermore, this risk score also showed association with immunocyte infiltration and drug sensitivity, revealing potential mechanisms for ubiquitination mediated OV risk. In addition, FBXO9, but not UBD, was found to be downregulated in OV and positively correlated with DNA damage repair pathways, suggesting FBXO9 as a potential cancer suppressor, likely via facilitating DNA damage repair. Conclusions: We identified and validated a signature of UbRGs that accurately predicts the prognosis, offers valuable guidance for optimizing chemotherapy and targeted therapies, and suggests a potential role for FBXO9 in OV.

Published in Biomolecules

ISSN: 2218-273X (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: https://www.mdpi.com/journal/biomolecules

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