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LATVIAN

BIOMEDICAL

RESEARCH AND STUDY CENTRE


RESEARCH AND EDUCATION IN BIOMEDICINE FROM GENES TO HUMAN

Project: Establishing an algorithm for the early diagnosis and follow-up of patients with pancreatic neuroendocrine tumors

Acronym: NExT

Call for proposal: Joint Transnational Call for Proposals 2017 (JTC 2017)

Contract number: 1.1.1.5/ERANET/20/03

Implementation period: 1 September 2019 – 28 February 2023

Project coordinator: Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V., Institute for Biomedical Engineering IBMT

Project partners:

Department of Medical Oncology, Ramon y Cajal University Hospital Health                Research Institute

Biomedical Research Center, Slovak Academy of Sciences, Cancer Research Institute

Latvian Biomedical Research and Study Centre

1st Departament of Propaedutic surgery, National and Kapodistrian university of Athens

Bioquochem company, Parque Tecnológico de Asturias

Leader of Latvian team: Dr. biol., Vita Rovīte

Total Costs: 210 000.00 EUR

Summary

Standardized clinical management of pancreatic neuroendocrine tumours (PNETs) is limited by different aspects of the disease, as its relative rarity (1 per 100,000 individuals), heterogeneous clinical presentation (hormonally functional or non-functional), the limited understanding of tumour biology and behaviour and the lack of prospectively evaluated risk stratification systems. While surgical excision remains the primary therapy, as early detection is uncommon, most patients present with metastatic disease at diagnosis and a reduced life expectancy as they are not candidates for resection.

Hypothesis: Prompt, specific and sensitive detection and characterisation of PNETs could lead to early detection, increasing the chance for surgical intervention and improve patients’ survival. Circulating tumour cells (CTCs) shed from primary tumours are considered attractive biomarkers for liquid biopsy as they represent an early step in blood-borne metastasis. Several studies propose that during malignant progression cancer cells undergo an epithelial-to-mesenchymal transition (EMT), acquire invasive properties and stem cell-like features.

Aims: The present proposal, by building up a tissue bank of genetically characterized tumours, development of patient-derived rare tumour xenografts (PDXs) and organoids, aim to identify PNET-specific biomarkers urgently needed to design a next generation nanotechnology based microfluidic device and integrate the technology of minimally invasive liquid biopsy in the early detection of PNETs.

Methods: Serum and tissue samples (fresh and FFPE) will be collected from PNET patients and their clinical and lab records will be recorded. An expression study and genomic analysis will be performed in clinical samples by different molecular techniques whereas in parallel organoids, PDX and CDX will be established. A next generation nanotechnology based microfluidic device will be developed, based on the acquired data.

Expected results and potential impact: Better understanding of the etiopathogenetic determinants involved in PNETs formation resulting from the multidisciplinary collaboration within ‘NExT” consortium will hopefully deliver a nanotechnology-based microfluidic (next generation) device that by means of CTCs detection will present a powerful tool for the early detection of PNET tumours and follow-up of patients, contributing to their better medical treatment.

1 January 2020- 31 March 2020

During the implementation period, the necessary documents have been prepared for submission to the Central Medical Ethics Committee in order to obtain an approval. Cooperation with major hospitals on collecting patient samples has been established.

Information published 31.03.2020.

1 April 2020- 30 June 2020

The approval of the Central Medical Ethics Committee was obtained during the implementation period. Continued cooperation with major hospitals on collecting patient samples. Communication with project partners on the delivery of samples for sequencing has been initiated.

Information published 30. 06.2020.

1 July 2020- 30 September 2020

Continued communication with project partners on sample delivery for sequencing. Optimization of the method for isolation and sequencing RNA from a small number of cells has been performed. Bioinformatics analysis optimization and literature studies for project need have been carried out.

Information published 30. 09.2020.

1 October 2020- 31 December 2020

Optimisation of bioinformatics analysis and literature studies on analysis of paraffined embedded tissue RNS sequencing has been started. Continued cooperation with major hospitals on collecting patient samples.

Information published 30. 12.2020.

1 January 2021- 31 March 2021

During the implementation period, the necessary documents have been prepared for submission to the Central Medical Ethics Committee in order to obtain an approval. Cooperation with major hospitals on collecting patient samples has been established.

Information published 31. 03.2021.

1 April 2021 – 30 June 2021

In this project implementation period, the analysis of paraffin-embedded tumour tissue has been continued (isolated nucleic acids, library preparation, sequencing). Bioinformatics analyses have been carried out on the obtained data. The pancreatic neuroendocrine tumour patient recruitment has started in Latvia, patients consented to the study and biological materials obtained.

Information published on 30. 06.2021.

1 July 2021 – 30 September 2021

In this project implementation period, the analysis of paraffin-embedded tumour tissue has been continued (isolated nucleic acids, library preparation, sequencing). Bioinformatics analyses have been carried out on the obtained data. The pancreatic neuroendocrine tumour patient recruitment has been continued in Latvia, patients consented to the study and biological materials obtained.

Information published on 30. 09.2021.

1 October 2021 – 31 December 2021

In this project implementation period, the analysis of paraffin-embedded tumour tissue has been continued (isolated nucleic acids, library preparation, sequencing). Bioinformatics analysis and optimization of the obtained sequencing data is continued. The pancreatic neuroendocrine tumour patient recruitment has been continued in Latvia, patients consented to the study and biological materials obtained.

Information published on 30. 12.2021.

1 January 2022 – 31 March 2022

The sequencing of paraffin-embedded tumour tissue acquired form project partners has been finished. Bioinformatics analysis and optimization of the obtained sequencing data is continued. The pancreatic neuroendocrine tumour patient recruitment has been continued in Latvia, patients consented to the study and biological materials obtained, the negotiations with Latvian pathology departments have been initiated to acquire retrospective paraffin-embedded tumour tissues for sequencing.

Information published 31.03.2022.

1 April 2022 – 30 June 2022

Paraffin-embedded tumour tissues from pancreatic neuroendocrine tumour patients in Latvia have been obtained in collaboration with Latvian pathology departments un currently the libraries for sequencing are being prepared for sequencing. Bioinformatics analysis of the obtained sequencing data is continued. The preparation of the publication has started.

Information published 30.06.2022.