Organoids as a model system for researching human neuroendocrine tumor of the breast

Background: Neuroendocrine tumors primarily consist of endocrine cells commonly located in neural tissue and the endocrine system. Primary neuroendocrine neoplasms of the breast are highly heterogeneous tumors characterized by a diverse cell population. Their rarity in the breast poses considerable challenges in studying their pathogenesis and developing effective treatments.

Methods: The surgical specimen was obtained from a Chinese female patient diagnosed with neuroendocrine tumor of the breast (NETB). We performed tissue histological staining and established NETB patient-derived organoids, which were subsequently used for histological staining, drug screen, and Single-cell RNA Sequencing.

Results: We successfully established NETB patient-derived organoids from a Chinese female patient. Histological staining showed that the morphological characteristics and the expression of molecular biomarkers (ER, PR, HER2, Ki67, Syn, CgA) in the NETB patient-derived organoids resembled those of the original tumor tissue. The NETB patient-derived organoids exhibited varying sensitivities to seven different drugs. Single-cell RNA Sequencing revealed significant heterogeneity and diverse molecular functions among these organoids.

Conclusions: This was the first instance of establishing an Organoid model for NETB. Due to high heterogeneity, this NETB patient-derived Organoid provides a robust foundation for clinical research. In the future, it could serve as a reliable tool for disease pathology diagnosis, drug screening, and genetic level studies.

Drug screen; Histological staining; Neuroendocrine neoplasms of the breast; Organoids; Single-cell RNA sequencing.