Single-cell Sequencing and Establishment of Models in Neuroendocrine Neoplasm

September 19, 2021 updated by: Xian-Jun Yu, Fudan University

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

The aim of this study is to use single-cell sequencing technology to explore neuroendocrine neoplasm (NEN) molecular biological characteristics, tumor heterogeneity and cell subtypes. Besides. NEN models are constructed for basic research, including primary cell lines, organoids, and animal models.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Recruiting
        • Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Collect specimens confirmed to be NEN or PDAC by surgery or biopsy histopathology for single-cell sequencing analysis and the construction of primary cells, organoids and animal models.

Description

Inclusion Criteria:

  1. Between the ages of 18 and 80, with any gender;
  2. Physical fitness score ECOG 0～1 points;
  3. The diagnosis is considered as gastrointestinal pancreatic neuroendocrine tumor or pancreatic ductal adenocarcinoma;
  4. There is no obvious contraindication to surgery or biopsy;
  5. Uncompensated liver cirrhosis, acute and chronic hepatitis and other diseases;
  6. No history of other biliary tract related diseases;
  7. Volunteer to participate and sign the informed consent form. -

Exclusion Criteria:

  1. Patients with non-gastrointestinal pancreatic neuroendocrine tumors or pancreatic ductal adenocarcinoma confirmed pathologically;
  2. Suffer from other digestive system diseases, such as irritable bowel syndrome, inflammatory bowel disease;
  3. Those who have incomplete follow-up data or refuse to accept follow-up;
  4. Patients with other malignant tumors or hematological diseases; -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Gastroenteropancreatic neuroendocrine neoplasms
Collect biopsy/surgical fresh tissue of gastroenteropancreatic neuroendocrine neoplasms.
Procedure: Biopsy, open or laparoscopic surgery
Collect NEN and PDAC biopsy or surgical fresh tissue to conduct single cell sequencing or model construction.
Pancreatic ductal adenocarcinoma
Collect biopsy/surgical fresh tissue of pancreatic ductal adenocarcinoma.
Procedure: Biopsy, open or laparoscopic surgery
Collect NEN and PDAC biopsy or surgical fresh tissue to conduct single cell sequencing or model construction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bioinformatics analysis of single-cell sequencing results
Time Frame: Half a year
Analysis of NEN Molecular Biology Information Using Single Cell Sequencing Technology
Half a year
Model construction
Time Frame: One year
Collect fresh specimens of NEN to cultivate primary cell lines, construct organoids, and establish animal models of NEN
One year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exploration of NEN organoid
Time Frame: One year
To explore and optimize the medium scheme of NEN orgnoid and methods of histomorphological identification of type organs
One year
Tumor microenvironment
Time Frame: One year
The tumor microenvironment of NEN was analyzed
One year
Comparison of mechanism of NEN with PDAC
Time Frame: Half a year
Collect fresh specimens of pancreatic ductal adenocarcinoma (PDAC) for single-cell sequencing and organoid construction for comparison with NEN
Half a year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Collaborators

D1 Medical Technology (Shanghai) Co., Ltd, China

Investigators

  • Principal Investigator: Xianjun Yu, MD, PhD, Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 6, 2021

Primary Completion (Anticipated)

June 1, 2022

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

June 2, 2021

First Submitted That Met QC Criteria

June 12, 2021

First Posted (Actual)

June 16, 2021

Study Record Updates

Last Update Posted (Actual)

September 24, 2021

Last Update Submitted That Met QC Criteria

September 19, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSPAC-NEN-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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