Combined proteomic/transcriptomic signature of recurrence post-liver transplantation for hepatocellular carcinoma beyond Milan
| Autor: | Gonzalo Sapisochin, Cristina Baciu, Sergi Clotet-Freixas, Ahmed Hammad, Ana Konvalinka, Tommy Ivanics, Mamatha Bhat, Sandra Fischer, Shelby Reid, Amirhossein Azhie, Anand Ghanekar, Marc Angeli, Elisa Pasini |
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| Rok vydání: | 2021 |
| Předmět: |
Combined signature
Oncology medicine.medical_specialty Proteome Hepatocellular carcinoma medicine.medical_treatment Clinical Biochemistry Context (language use) Milan criteria Liver transplantation 03 medical and health sciences 0302 clinical medicine Predictors of recurrence Internal medicine medicine Molecular Biology Survival analysis 030304 developmental biology 0303 health sciences Univariate analysis Tumor explant biology business.industry Research General Medicine medicine.disease 3. Good health ALDH1A1 030220 oncology & carcinogenesis biology.protein Molecular Medicine Immunohistochemistry Transcriptome business |
| Zdroj: | Clinical Proteomics |
| ISSN: | 1559-0275 1542-6416 |
| Popis: | Background and aims Liver transplantation (LT) can be offered to patients with Hepatocellular carcinoma (HCC) beyond Milan criteria. However, there are currently limited molecular markers on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to derive a combined proteomic/transcriptomic signature on HCC explant predictive of recurrence post-transplant using unbiased, high-throughput approaches. Methods Patients who received a LT for HCC beyond Milan criteria in the context of hepatitis B cirrhosis were identified. Tumor explants from patients with post-transplant HCC recurrence (N = 7) versus those without recurrence (N = 4) were analyzed by mass spectrometry and gene expression array. Univariate analysis was used to generate a combined proteomic/transcriptomic signature linked to recurrence. Significantly predictive genes and proteins were verified and internally validated by immunoblotting and immunohistochemistry. Results Seventy-nine proteins and 636 genes were significantly differentially expressed in HCC tumors with subsequent recurrence (p Conclusions Significantly increased LGALS3 and LGALS3BP gene and protein expression on explant were associated with post-transplant recurrence, whereas increased ALDH1A1 was associated with absence of recurrence in patients transplanted for HCC beyond Milan criteria. This combined proteomic/transcriptomic signature could help in predicting HCC recurrence risk and guide post-transplant surveillance. |
| Databáze: | OpenAIRE |
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