Role of the brain derived neurotrophic factor and inflammatory mediators in colon cancer

Syrina Mehrabi

Research output: ThesisDoctoral Thesis (compilation)

146 Downloads (Pure)

Abstract

CRC is one of the most common causes of cancer death in the world. If CRC is diagnosed in the early stages, the patient's chance of survival is estimated at about 90%, with a very low probability of recurrence. The five-year DFS for CRC patients in stage III and IV drops to 63.3% and 18.9%, respectively. The current thesis aimed to identify potential new prognostic and predicting biomarkers for the detection of patients in the early stages of colon cancer.
In particular, this thesis:
1) studies the role of BDNF expression in stage II and III CC. By examining human biopsies, in vivo, and in vitro experiments, this study, to the best of our knowledge, for the first time shows a positive correlation between expression of CD66b, CysLT1R, and BDNF. This study suggests BDNF, alone or in combination with other known molecular markers, as a good candidate to be prognostic and predictive biomarker for early detection of CC.
2) consider the problem of therapeutic resistance in CC patients and investigate the role of intermittent p-TrkB expression between the cytoplasm and nucleus. The results show that the cytoplasmic expression of TrkB and nuclear expression of CysLT1R are associated with poorer survival in CC patients. We also highlight the importance of further investigations of the role of TrkB expression in CC development
3) identifies a five-gene signature as a primary prognostic and diagnostic biomarker, in 5 independent published datasets for CRC patients in-silico. In all datasets, four tumorigenic genes (BDNF, PTGS2, GSK3B, and CTNNB1) are shown to be significantly upregulated and one tumor suppressor gene (HPGD) was significantly downregulated. The four suppressive tumorigenic genes were studied in the plasma of CRC patients to evaluate the diagnostic value in the disease. The results of this study showed that the suggested five-panel gene signature, with high accuracy, can be a promising indicator for predicting OS and RFS in patients with CRC. In addition, this study suggested the four highly sensitive tumor suppressor genes as potential diagnostic markers for CRC patients.
4) investigates altered expression of estrogen receptor beta (ERβ) in CRC. High expression of ERβ is shown to correlate with antitumorigenic activity, and a higher level of CysLT2R, membrane β-catenin, and 15-hydroxy prostaglandin dehydrogenase (15-PGDH) expression, as well as lower levels of CysLT1R, COX-2, and nuclear β-catenin. The current study confirmed the antitumor role of ERb-041 (an ERβ agonist), which corresponded to an inferior ability of the tumor cells to migrate, colonize and survive, including an increased apoptosis.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Department of Translational Medicine
Supervisors/Advisors
  • Sjölander, Anita, Supervisor
  • Satapathy, Shakti Ranjan, Assistant supervisor
Award date2022 Jan 28
Place of PublicationLund
Publisher
ISBN (Print)978-91-8021-171-0
Publication statusPublished - 2022

Bibliographical note

Defence details
Date: 2022-01-28
Time: 13:15
Place: Medelhavet, Inga Marie Nilssons gata 53, ingång 46, Skånes Universitetssjukhus i Malmö. Join by Zoom: https://lu-se.zoom.us/j/67637113520
External reviewer(s):
Name: Landström, Maréne
Title: professor
Affiliation: Medical Biosciences, Pathology, Umeå University, Umeå, Sweden

Subject classification (UKÄ)

  • Clinical Medicine

Free keywords

  • Colon Cancer, Neutrophils, Inflammation, CysLT1R, BDNF, Tumor microenvironment, Prognostic, Predictive, Diagnostic, Gene signature, Biomarkers

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