L1 ORF1p Is an Early Diagnostic Marker of Cancer and Its Precursor Syndromes
  • Metaadatok
Tartalom: https://doktori.bibl.u-szeged.hu/id/eprint/12583/
Archívum: SZTE Doktori Értekezések Repozitórium
Gyűjtemény: Tudományterületek = Orvostudományok: Egészségtudományok
Típus = Disszertáció
Cím:
L1 ORF1p Is an Early Diagnostic Marker of Cancer and Its Precursor Syndromes
Létrehozó:
Abdullah Khaldoon Sadiq Ahmed
Dátum:
2025
Téma:
03.01.08.06. Általános kórtan
03.02.21.04. Rák és annak biológiai alapja
Tartalmi leírás:
Cancer is currently the second leading cause of death in the European Union, following cardiovascular diseases. In recent years, its incidence has risen, largely due to an aging population, which places a significant burden on healthcare systems and society. Several studies have shown that the development of cancer is directly linked to the activity of L1 (L1) elements, the only currently active mobile genetic elements in the human genome, which make up about 17% of it. While most L1 elements are inactive due to mutations, some remain active and may contribute to genomic instability, influence gene expression, and potentially lead to diseases, including cancer. This thesis investigates the expression pattern of the ORF1p protein, encoded by L1, in various human cancers and explores its potential as a diagnostic biomarker. Using immunohistochemistry on tissue microarrays, the study analyzed 590 samples from 21 different tumor types, as well as samples from cervical intraepithelial neoplasia (CIN) and normal tissues. The results revealed that L1-ORF1p is minimally expressed in most normal somatic tissues but is frequently expressed in a wide range of cancers, including cervical cancer, non-small cell lung cancer, esophageal cancer, and basal cell carcinoma of the skin. Elevated L1-ORF1p expression was notably associated with higher clinical stages and histological grades, indicating a link to cancer progression. Moreover, intratumoral heterogeneity in L1-ORF1p expression was observed, with higher expression in less differentiated tumor areas. The study found a significant correlation between L1-ORF1p overexpression and mutations in tumor suppressor genes, particularly TP53. Tumors with mutated TP53 exhibited higher levels of L1-ORF1p than those with wild-type TP53, suggesting that the loss of function of TP53 may promote L1 activation and contribute to oncogenesis. This relation was confirmed by our experiments in tissue culture, where we found that silencing endogenous TP53 with artificial microRNAs (amiRs) increased the number of L1 retrotransposition events. The findings suggest that L1-ORF1p is a novel biomarker for both cancer diagnosis and prognosis. Its expression patterns could help distinguish between low and high-grade lesions, potentially improving diagnostic accuracy and patient management. Additionally, targeting L1-ORF1p could offer new therapeutic options in cancer treatment. The study highlights the importance of further research to elucidate the mechanisms through which L1 activity contributes to tumorigenesis and to explore its potential clinical applications.
Nyelv:
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Típus:
Disszertáció
NonPeerReviewed
Formátum:
application/pdf
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application/pdf
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Azonosító:
Abdullah Khaldoon Sadiq Ahmed L1 ORF1p Is an Early Diagnostic Marker of Cancer and Its Precursor Syndromes. Doktori értekezés, Szegedi Tudományegyetem (2000-). (2025)
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