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

Abstract

Abstract 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.

Keywords

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