This study first reveals the dynamic changes in serum branched-chain amino acid (BCAA) levels in patients with differentiated thyroid cancer (DTC) following radioactive iodine therapy, offering potential alternative biomarkers for treatment evaluation in cases of Tg/Ab interference. Additionally, the research validates the association between CD98hc expression and BCAA uptake in TPC-1 cell models, providing a theoretical foundation for subsequent targeted studies.
Literature Overview
The article 'CD98hc-regulated BCAA Metabolism in Radioactive Iodine Therapy for Differentiated Thyroid Cancer' published in Oncology Reports reviews metabolic alterations in serum metabolites of DTC patients pre- and post-radioactive iodine therapy, and investigates the molecular mechanisms linking amino acid transporter activity with treatment response using TPC-1 cell models. The study focuses on BCAA metabolic shifts and their correlation with L-type amino acid transporter (LAT1/CD98hc) expression, aiming to identify Tg/Ab-independent biomarkers for therapy monitoring.
Background Knowledge
Differentiated thyroid cancer (DTC) represents the predominant subtype of thyroid malignancies, with standard treatment involving total thyroidectomy and radioactive iodine (131I) ablation. However, thyroglobulin (Tg) measurements are frequently compromised by Tg/Ab interference, necessitating the search for Tg/Ab-independent biomarkers. Branched-chain amino acids (BCAAs), essential amino acids whose metabolic levels are often associated with tumor proliferation, are transported via the LAT1/CD98hc complex, a marker of metabolic activity in multiple cancers. This study employs liquid chromatography-mass spectrometry (LC-MS/FIA-MS) and TPC-1 cell models to evaluate BCAA uptake and CD98hc expression changes after ionizing radiation (IR), establishing a foundation for novel therapeutic monitoring strategies.
Research Methods and Experiments
The study enrolled 3 DTC patients receiving radioactive iodine therapy combined with recombinant human TSH (rhTSH) stimulation. Serum samples were collected pre- and post-treatment for metabolomic analysis. TPC-1 cells underwent 8 Gy ionizing radiation (IR), followed by BPA uptake assays to evaluate LAT1-mediated amino acid transport activity and flow cytometry to assess CD98hc surface antigen expression. RT-qPCR quantified LAT1, LAT2, and CD98hc mRNA expression to investigate radiation-induced transporter regulation.
Key Conclusions and Perspectives
Research Significance and Prospects
This work provides preliminary evidence for alternative biomarkers in Tg/Ab-interfered scenarios, supporting BCAA as a candidate for DTC treatment monitoring. The upregulation of CD98hc highlights its functional relevance in IR response, warranting further investigation into LAT1/CD98hc's role in radioactive iodine therapy and their potential as therapeutic targets. These findings establish a framework for integrating clinical metabolomic analyses with cellular models to explore transporter dynamics.
Conclusion
Collectively, this study demonstrates BCAA level dynamics following radioactive iodine therapy and confirms the CD98hc-BCAA uptake relationship in TPC-1 cells. While LAT1/CD98hc mRNA expression remains unchanged, elevated CD98hc protein levels may enhance BCAA uptake, underscoring its role in cellular stress adaptation. These results identify BCAA as a promising metabolic biomarker for DTC patients with Tg/Ab interference and provide theoretical support for developing LAT1/CD98hc-targeted therapeutic strategies. Future studies should validate the clinical utility of serum BCAA changes in larger cohorts and combine membrane protein analysis with functional assays to elucidate IR-induced transporter regulation mechanisms.
