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Profiling Extracellular Vesicle Proteome of Small Cell Lung Cancer Patients for Non-Invasive Subtyping and Monitoring

Nayak, Aadya (2024) MOBN02 20232
Degree Projects in Molecular Biology
Abstract
Small cell lung cancer (SCLC) is a highly aggressive form of cancer, characterized by a particularly poor prognosis. Subsequently, it has a very low five-year survival rate of only 6%. At the clinic, patients are either diagnosed at advanced stages where care is more palliative and with few therapeutic options or, when diagnosed at earlier stages, respond very positively to first-line treatments but relapse soon after—often with a more aggressive and consequently fatal presentation. A major obstacle in clinical care is how fast SCLC progresses, combined with the lack of knowledge regarding any prognostic or diagnostic biomarkers for the same. More importantly, biomarkers that can be linked to any targeted therapy are still lacking in SCLC.... (More)
Small cell lung cancer (SCLC) is a highly aggressive form of cancer, characterized by a particularly poor prognosis. Subsequently, it has a very low five-year survival rate of only 6%. At the clinic, patients are either diagnosed at advanced stages where care is more palliative and with few therapeutic options or, when diagnosed at earlier stages, respond very positively to first-line treatments but relapse soon after—often with a more aggressive and consequently fatal presentation. A major obstacle in clinical care is how fast SCLC progresses, combined with the lack of knowledge regarding any prognostic or diagnostic biomarkers for the same. More importantly, biomarkers that can be linked to any targeted therapy are still lacking in SCLC. However, to screen for such biomarkers requires a large amount of tissue sample, which cannot be implemented with SCLC as there are resection size restrictions due to the advanced stage of many cases at diagnosis and repeated biopsies would also significantly detriment patient quality of life.

This project evaluates the viability of a liquid biopsy setup to identify SCLC-relevant biomarkers from extracellular vesicles (EVs), which are lipid bilayer-enclosed carriers of a large variety of cellular information, to bypass the bottlenecks abovementioned in better characterizing SCLC at a molecular level. To test this hypothesis, we optimized a protocol for protein sourcing and characterization from plasma EVs and ran a large cohort of SCLC samples (n = 567) sourced from the RASTEN randomized clinical trial (Ek et al., 2018), through this pipeline. While results are still preliminary, we were able to cluster samples on the basis on overall expression profiles and screened 6 proteins with differential expression between baseline and treatment at cycle 3 of the RASTEN trial standard treatment protocol. If successfully adapted to the clinical front, these findings could help expand our understanding of and medical care for SCLC. (Less)
Popular Abstract
A Liquid Solution to a Solid Problem: Profiling Small Cell Lung Cancer Non-Invasively through Extracellular Vesicles

Imagine an epic traffic jam in an action movie—with cars, motorbikes, and pedestrians alike running every which way. Cancers are not so different. They are immensely complex diseases that use a wide range of cells and signaling molecules to aid in their progression, and targeting these molecules with different kinds of treatments is a primary front in anti-cancer therapy.

With such a large traffic scene, each of these elements could be the key to solving the traffic efficiently. But the question is: Which car? Which motorbike? Which pedestrian? And how exactly do we find them?

Small Cell Lung Cancer (SCLC) is a... (More)
A Liquid Solution to a Solid Problem: Profiling Small Cell Lung Cancer Non-Invasively through Extracellular Vesicles

Imagine an epic traffic jam in an action movie—with cars, motorbikes, and pedestrians alike running every which way. Cancers are not so different. They are immensely complex diseases that use a wide range of cells and signaling molecules to aid in their progression, and targeting these molecules with different kinds of treatments is a primary front in anti-cancer therapy.

With such a large traffic scene, each of these elements could be the key to solving the traffic efficiently. But the question is: Which car? Which motorbike? Which pedestrian? And how exactly do we find them?

Small Cell Lung Cancer (SCLC) is a highly aggressive type of cancer, characterized by poor prognosis and low survival. A major cause for this has been a lack of identified biomarkers, which would help diagnose it faster and treat it more effectively. Unfortunately, because a large portion of SCLC cases are diagnosed at a very advanced stage, it is difficult to source sufficient tumor material to screen SCLC-specific biomarkers. Moreover, the procedure is invasive and can reduce patient quality of life.

This project proposes using a liquid biopsy from peripheral blood as a potential alternative to better understand and monitor SCLC for biomarkers. Among the many potential targets that could be screened from blood, we focused on extracellular vesicles (EVs) as they are both structurally robust and can carry various types of signaling molecules.

To evaluate whether EVs can be used to molecularly profile SCLC, we optimized a pipeline involving EV isolation and characterization from a randomized clinical trial biobank, liquid chromatography, and mass spectrometry to screen proteins that should be specific to SCLC EVs.

While analysis is still ongoing, our preliminary results show that we were able to screen 1300+ proteins (which could be organized into molecular profiles based on relative protein expression) as well as identify proteins with differential expression between two time points in patient treatment. Although our results need further validation with clinical data, they are an indication that this method can be used to enrich our understanding of SCLC and improve its medical care.

Master’s Degree Project in Molecular Biology, 45 credits, 2024
Department of Biology, Faculty of Science, Lund University

Advisor: Prof. Mattias Belting
Department of Clinical Sciences, Faculty of Medicine, Lund University (Less)
Please use this url to cite or link to this publication:
author
Nayak, Aadya
supervisor
organization
course
MOBN02 20232
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9176962
date added to LUP
2024-10-23 11:46:33
date last changed
2024-10-23 11:46:33
@misc{9176962,
  abstract     = {{Small cell lung cancer (SCLC) is a highly aggressive form of cancer, characterized by a particularly poor prognosis. Subsequently, it has a very low five-year survival rate of only 6%. At the clinic, patients are either diagnosed at advanced stages where care is more palliative and with few therapeutic options or, when diagnosed at earlier stages, respond very positively to first-line treatments but relapse soon after—often with a more aggressive and consequently fatal presentation. A major obstacle in clinical care is how fast SCLC progresses, combined with the lack of knowledge regarding any prognostic or diagnostic biomarkers for the same. More importantly, biomarkers that can be linked to any targeted therapy are still lacking in SCLC. However, to screen for such biomarkers requires a large amount of tissue sample, which cannot be implemented with SCLC as there are resection size restrictions due to the advanced stage of many cases at diagnosis and repeated biopsies would also significantly detriment patient quality of life. 

This project evaluates the viability of a liquid biopsy setup to identify SCLC-relevant biomarkers from extracellular vesicles (EVs), which are lipid bilayer-enclosed carriers of a large variety of cellular information, to bypass the bottlenecks abovementioned in better characterizing SCLC at a molecular level. To test this hypothesis, we optimized a protocol for protein sourcing and characterization from plasma EVs and ran a large cohort of SCLC samples (n = 567) sourced from the RASTEN randomized clinical trial (Ek et al., 2018), through this pipeline. While results are still preliminary, we were able to cluster samples on the basis on overall expression profiles and screened 6 proteins with differential expression between baseline and treatment at cycle 3 of the RASTEN trial standard treatment protocol. If successfully adapted to the clinical front, these findings could help expand our understanding of and medical care for SCLC.}},
  author       = {{Nayak, Aadya}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Profiling Extracellular Vesicle Proteome of Small Cell Lung Cancer Patients for Non-Invasive Subtyping and Monitoring}},
  year         = {{2024}},
}