Blood-based transcriptomic biomarkers for response to [¹⁷⁷Lu]Lu-DOTA-TATE therapy in neuroendocrine tumors

[¹⁷⁷Lu]Lu-DOTA-TATE is an effective treatment for metastatic neuroendocrine tumors (NETs) expressing somatostatin receptors. While the tumor uptake [¹⁷⁷Lu]Lu-DOTA-TATE of has shown potential as a predictive biomarker, patient response to the treatment varies significantly. In this study, we aim to identify a predictive blood-based transcriptomic biomarker to better understand individual responses to [¹⁷⁷Lu]Lu-DOTA-TATE therapy.

Twenty-six patients were prospectively enrolled in this study. Responders were defined as patients who showed partial response or stable disease and non-responders were defined as patients who showed progressive disease according to RECIST1.1 criteria. Of the 26 patients, responders (n = 20) exhibited distinct gene expression profiles compared to non-responders (n = 6). Among the 21 differentially expressed genes identified between the groups, 13 genes were upregulated in non-responders and were associated with the innate immune system. Weighted Gene Co-expression Network Analysis identified a significant gene module linked to treatment response, with eEF1A1 emerging as a key hub gene correlated with favorable outcomes. Baseline clinical and laboratory parameters did not differ significantly according to treatment response.

This study identifies specific blood transcriptomic profiles associated with the innate immune response and a key hub gene linked to treatment outcomes, suggesting an immune-related component in response to [¹⁷⁷Lu]Lu-DOTA-TATE therapy. These findings may guide patient selection based on systemic immune markers and inform future therapeutic strategies.