Document
Identification of potential immune checkpoint biomarkers for human papillomavirus associated cervical cancer.
Source
Master's thesis
Other titles
تحديد المؤشرات الحيوية المحتملة لنقاط التفتيش المناعية لسرطان عنق الرحم المرتبط بفيروس الورم الحليمي البشري
Country
Oman
City
Muscat
Publisher
Sultan Qaboos University
Gregorian
2024
Language
English
Thesis Type
Master's thesis
English abstract
Cervical cancer is leading to death among women worldwide and the primary cause of cervical
cancer is human papillomavirus (HPV) infection. The heterogeneity of patients in various
aspects, such as tumorigenesis, body immune response and immune evasion mechanisms by
different virus subtypes, represent a challenge to achieve effective prevention and precise
treatment. Therefore, it has become a global concern to screen for biomarkers and therapeutic
target for HPV associated cervical cancer that are less toxic agents and improve survival rate. In
the present study, we sought to identify potential immune related biomarkers based on publicly
available transcriptomic, and epigenetic datasets and study their correlation with immune cell
infiltration and finally study their expression in different high-risk HPV subtypes. Initially, we
identified 328 differentially expressed genes and 830 differentially methylated genes. Analysis
showed that those genes are involved in the defense response process and Human T-cell
leukemia virus 1 infection pathway. Twenty genes were found to be immune checkpoint genes
and therefore are potential biomarkers that may play a crucial role in HPV associated cervical
cancer. Using enrichment based on publication, we found that these biomarkers are involved in
CD8 T-cell, Tregs cell, Natural killer cell pathways and immunotherapy targets. Notably, most
of the ICGs correlated with CD8 T-cell and NK cell infiltration. Furthermore, the expressions of
KDR, SMAD3, WNT9A, IL15, FOXP3 and CD96 showed different expression levels between
high-risk HPV subtypes. Thus, these biomarkers may enable better response for targeted
immunotherapy.
Arabic abstract
يؤدي سرطان عنق الرحم إلى الوفاة بين النساء في جميع أنحاء العالم و السبب الرئيسي لسرطان عنق الرحم هو عدوى فيروس الورم الحليمي البشري. يمثل عدم تجانس المرضى في جوانب مختلفة ، مثل تكوين الاورام والاستجابة المناعية للجسم وآليات الهرب المناعي عن طريق الأنواع الفرعية المختلفة من الفيروس تحديا لتحقيق الوقاية الفعالة والعلاج الدقيق. لذلك أصبح البحث عن مؤشر حيوي وعلاجي لسرطان عنق الرحم المرتبط بفيروس الورم الحليمي الذي قد يؤدي إلى زياده معدل البقاء على قيد الحياة يشكل قلقا عالمياً.
Category
Theses and Dissertations