Desterke, C.; Francés, R.; Monge, C.; Marchio, A.; Pineau, P.; Mata-Garrido, J. Combined Expression of DNMT3B and PFKFB4 in Hepatoblastoma Predicts Metastatic Outcome. Preprints2024, 2024091115. https://doi.org/10.20944/preprints202409.1115.v1
APA Style
Desterke, C., Francés, R., Monge, C., Marchio, A., Pineau, P., & Mata-Garrido, J. (2024). Combined Expression of DNMT3B and PFKFB4 in Hepatoblastoma Predicts Metastatic Outcome. Preprints. https://doi.org/10.20944/preprints202409.1115.v1
Chicago/Turabian Style
Desterke, C., Pascal Pineau and Jorge Mata-Garrido. 2024 "Combined Expression of DNMT3B and PFKFB4 in Hepatoblastoma Predicts Metastatic Outcome" Preprints. https://doi.org/10.20944/preprints202409.1115.v1
Abstract
(1) Background: Hepatoblastoma is the most common primary liver cancer in children. Nowadays, poor outcome occurs essentially for patients with distant metastases; (2) Methods: Starting from Mammalian Metabolic Enzyme Database over expression of metabolic enzymes was searched in hepatoblastoma tumors as compared to noncancerous liver tissue in transcriptome dataset GSE131329. With overexpressed enzymes, Elasticnet machine learning tuning was performed according to metastasis status outcome. With significant enzymes a metabolic expression score was computed and integrated in multivariate clinical-biological logistic model; (3) Results: Forty-one overexpressed enzymes discriminate hepatoblastoma tumors and noncancerous liver tissues. Eighteen of them predict metastasis status (AUC 0.90) with 85.7% of sensibility and 92.3% of specificity. Elasticnet machine learning model tuning highlighted major importance of DNMT3B and PFKFB4 expression to predict metastasis. Role of these two enzymes was confirmed by univariate analyses with respective p-values: 0.0058 and 0.0091. Metabolic score computed with combined expression of DNMT3B and PFKFB4 discriminates metastasis status and high-risk CHIC score by univariate analysis (p-value=0.005). Meta.score was found more sensitive than C1/C2 classifier to predict metastasis status (accuracy: 0.72 versus 0.55). Integration of meta.score (DNMT3B, PFKFB4) with epidemiological parameters: gender, age at diagnosis, histological types, and clinical PRETEXT stages in a multivariate model confirmed independent adverse role of meta.score to predict metastasis status (multivariate p-value=0.003, odds ratio: 2.12); (4) Conclusions: Based on metabolic enzyme expression program of hepatoblastoma, we characterized a dual overexpression of PFKFB4 and DNMT3B in samples of patients at risk of metastasis (High risk CHIC stratification). With combined tumor expression of DNMT3B and PFKFB4 a meta.score was computed and this parameter was confirmed as an independent adverse score to predict metastatic status during hepatoblastoma.
Keywords
Hepatoblastoma; Metastasis; CHIC Risk; Metabolism; Epigenetics; DNA Methylation; Glycolysis; Transcriptome
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
