Reference - Detail
| RRC ID | 85870 |
|---|---|
| Author | Oura K, Morishita A, Yano R, Manabe T, Takuma K, Nakahara M, Tadokoro T, Fujita K, Mimura S, Tani J, Tatsuta M, Himoto T, Masaki T, Kobara H. |
| Title | Circulating miR-485-3p as a biomarker for VEGF-associated therapeutic response to atezolizumab plus bevacizumab in hepatocellular carcinoma. |
| Journal | J Gastroenterol |
| Abstract |
BACKGROUND:In atezolizumab/bevacizumab (atezo/bev) therapy for unresectable hepatocellular carcinoma (HCC), the tumor immune environment is regulated through vascular endothelial growth factor A (VEGFA) inhibition to maximize immune checkpoint blockade; however, evidence for VEGFA as a biomarker is limited. This study aimed to investigate serum VEGFA and associated microRNAs (miRNAs) as rapid biomarkers and their regulatory mechanisms in the microenvironment of HCC. METHODS:Fifty-four patients with unresectable HCC who were treated with atezo/bev therapy were enrolled and assigned into objective response (OR) and non-OR groups according to the best therapeutic response in 12 weeks using the modified response evaluation criteria in solid tumors. Serum VEGFA levels and associated miRNA expression were compared. Furthermore, the effect of cell transfection with specific miRNA was investigated. RESULT:There was no significant difference in the pre-treatment serum VEGFA levels between the groups; however, the 3-week/pre-treatment ratio of serum VEGFA levels was significantly lower in the OR group than in the non-OR group. The pre-treatment serum levels of 10 miRNAs, especially miR-485-3p involved in VEGFA expression, were higher in the OR group than in the non-OR group and were further elevated after 1-7 days and 3 weeks. MiR-485-3p suppressed HuH-7 migration, enhanced the expression of protein inhibitor of activated (PIA) signal transducer and activator of transcription 3 (STAT3) (PIAS3), and suppressed the expression of phosphorylated STAT3/VEGFA. CONCLUSION:Circulating miR-485-3p is a more sensitive biomarker than VEGFA for the early prediction of therapeutic response in atezo/bev therapy for HCC. |
| Volume | 60(6) |
| Pages | 770-782 |
| Published | 2025-6-1 |
| DOI | 10.1007/s00535-025-02239-7 |
| PII | 10.1007/s00535-025-02239-7 |
| PMID | 40180668 |
| MeSH | Aged Antibodies, Monoclonal, Humanized / administration & dosage Antibodies, Monoclonal, Humanized / therapeutic use Antineoplastic Combined Chemotherapy Protocols* / administration & dosage Antineoplastic Combined Chemotherapy Protocols* / therapeutic use Bevacizumab / administration & dosage Bevacizumab / therapeutic use Biomarkers, Tumor / blood Carcinoma, Hepatocellular* / blood Carcinoma, Hepatocellular* / drug therapy Carcinoma, Hepatocellular* / genetics Carcinoma, Hepatocellular* / pathology Female Humans Liver Neoplasms* / blood Liver Neoplasms* / drug therapy Liver Neoplasms* / genetics Liver Neoplasms* / pathology Male MicroRNAs* / blood Middle Aged STAT3 Transcription Factor / metabolism Treatment Outcome Tumor Microenvironment Vascular Endothelial Growth Factor A* / blood |
| IF | 6.132 |
| Resource | |
| Human and Animal Cells | HuH-7(RCB1366) |