Single-cell Sequencing and Establishment of Cell Lines, Organoids, and Transplanted Tumor Models in Neuroendocrine Neoplasm

Neuroendocrine neoplasm (NEN) generally refers to all tumors that originate from peptidergic neurons and neuroendocrine cells. It is a relatively rare tumor, ranging from indolent, slow-growing low-grade malignant tumors to obvious distant metastases. A series of malignant tumors. The most common place for neuroendocrine tumors is in the digestive system, and about two-thirds of neuroendocrine tumors occur in the gastrointestinal pancreas. However, with the change of people's living habits and the improvement of physical examination awareness, the incidence of neuroendocrine tumors increased from 1.09/100,000 in 1973 to 6.98/100,000 in 2012. The incidence has increased by 6 times compared with other tumors. , NENs increase more rapidly. The incidence of people over 65 years of age has increased by 8 times, and the incidence of people younger than 50 years of age has also increased by 3 times, and the incidence has been increasing year by year. It is worth noting that the average age of pancreatic neuroendocrine tumors is only 56.7-13.3 years old, showing a younger trend.

Because most neuroendocrine tumors lack specific manifestations, coupled with unique inert biological characteristics, clinicians often lack understanding, which can easily lead to misdiagnosis and treatment. Taking gastrointestinal pancreatic neuroendocrine tumors (GEP-NEN) as an example, due to the uneven diagnosis and treatment level, GEP-NEN patients may be diagnosed with a delay of up to 7 years. Because of this, as many as 40-95% of GEP-NEN patients have developed distant metastases at the time of diagnosis, and 65-95% of them have liver metastases. Liver metastasis is the most critical prognostic risk factor in GEP-NEN, and it has a decisive impact on the survival of patients. The 5-year survival rate of gastrointestinal neuroendocrine tumors with liver metastasis is 56%-83%, while the 5-year survival rate of pancreatic neuroendocrine tumors is only 48.8%, and the 10-year survival rate is only 30.2%. For limited-stage patients, even if radical surgical resection, up to 94% of cases will still have recurrence and metastasis within 5 years. For inoperable patients, although chemotherapy, targeted therapy, biological therapy and other methods can be used, the effect is still limited. Therefore, the systematic development of basic-clinical translational research on neuroendocrine tumors is very important and imminent.

Based on the above-mentioned problems, this project intends to conduct a systematic and in-depth study of neuroendocrine tumors: 1. Use single-cell sequencing technology to deeply study the molecular biological characteristics of NEN tumors, tumor heterogeneity and cell subtypes. 2. Construct NEN models, including primary cell lines, organoids, and mouse animal models. This study can establish a neuroendocrine tumor research system to find the molecular mechanism and potential intervention targets of NEN recurrence and metastasis, and provide clinicians with safe and effective treatment strategies, thereby improving the therapeutic effect of neuroendocrine tumors.