Introduction: Tripartite motif-containing protein (TRIM) family members play crucial roles in carcinogenesis and chemotherapy resistance. In this study, we aimed to determine whether TRIM58 protein expression is related to patient responses to neoadjuvant therapy (NAT) and their survival outcome.
Methods: Immunohistochemistry was performed on female breast cancer samples from biopsies before NAT in Shenzhen Second People's Hospital. Univariate and multivariate logistic regression tests were used to analyze the association between TRIM58 protein expression and pathological complete response (pCR). The Cox proportional hazards model was used to calculate the adjusted hazard ratio (HR) with a 95% confidence interval (95% CI). The Kaplan-Meier plotter database was used to analyze the prognostic value of TRIM58.
Results: High TRIM58 expression was associated with small tumor size in all the patients (n = 58). Multivariate analysis suggested that low TRIM58 expression was an independent predictive factor for higher pCR (odds ratio = 0.06, 95% CI 0.005-0.741, = 0.028). The Kaplan-Meier Plotter dataset suggested that the TRIM58 high-expression group showed a worse 5-year overall survival than the low-expression group (HR = 1.34, 95% CI 1.07-1.67, = 0.01). Pathway analysis revealed the potential mechanisms of TRIM58 in chemoresistance.
Discussion: Our study suggests that TRIM58 is a promising biomarker for both neoadjuvant chemosensitivity and long-term clinical outcomes in breast cancer. It may also help to identify candidate responders and determine treatment strategies.
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http://dx.doi.org/10.2147/BCTT.S387209 | DOI Listing |
Ann Clin Lab Sci
November 2024
Department of Thoracic Surgery, First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Objective: To identify key genes associated with the prognosis of non-small cell lung cancer (NSCLC) through bioinformatics analysis and experimental validation, exploring the expression of the TRIM58 gene and its potential effect as a tumor suppressor.
Methods: In this study, differentially expressed genes (DEGs) and differentially methylated genes (DMGs) related to lung adenocarcinoma and lung squamous cell carcinoma were selected from the TCGA dataset, with the Limma package in R software used for further filtering and intersection, followed by the assessment of the relationship between these genes and NSCLC prognosis using log-rank tests and univariate Cox regression analysis. Meanwhile, six clinical NSCLC cancer and adjacent tissue samples were collected, along with the detection of TRIM58 mRNA and protein levels using RT-PCR and Western blot.
J Biol Chem
January 2025
Department of Pediatrics, Dana Farber/Boston Children's Hospital Cancer and Blood Disorder Center, Boston, Massachusetts, USA; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA; Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts, USA. Electronic address:
Targeted protein degradation (TPD) mediated by proteolysis targeting chimeras or molecular glues is an emerging therapeutic strategy. Despite greater than 600 E3 ligases and their associated components, a limited number have been deployed in TPD. Those commonly used include cereblon and von Hippel-Lindau tumor suppressor (VHL), which is expressed widely and for which high affinity ligands are available.
View Article and Find Full Text PDFCurr Pharm Des
June 2024
Department of Gastrointestinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Background: Colon cancer is a common tumor in the gastrointestinal tract with a poor prognosis. According to research reports, ubiquitin-dependent modification systems have been found to play a crucial role in the development and advancement of different types of malignant tumors, including colon cancer. However, further investigation is required to fully understand the mechanism of ubiquitination in colon cancer.
View Article and Find Full Text PDFCancer Gene Ther
August 2024
Department of Oncology, Ningbo No.2 Hospital, Ningbo, Zhejiang, PR China.
TRIM58 is a member of the TRIM protein family, which possess with E3 ubiquitin ligase activities. Studies have revealed that low expression of TRIM58 plays key roles, has been implicated in the tumor progression of tumor formation due to its reduced expression. However, its role in regulating the stemness of breast cancer stem cells (CSCs) remains unexplored.
View Article and Find Full Text PDFACS Med Chem Lett
January 2024
Department of Protein Evolution, Max Planck Institute for Biology Tübingen, 72076 Tübingen, Germany.
Tissue-specific manipulation of proteins is a long-standing objective in the field of targeted protein degradation, but still a distant prospect. Currently, the most successfully employed E3 ubiquitin ligases belong to the most ubiquitously expressed representatives. Unlocking of the TRIM58 ligase might represent a promising step toward tissue-specific PROTACs and molecular glue degraders.
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