Title
Značaj epitelno-mezenhimalne tranzicije u kolorektalnoj karcinogenezi
Creator
Ranković, Branislava, 1980-
CONOR:
19146343
Copyright date
2021
Object Links
Select license
Autorstvo 3.0 Srbija (CC BY 3.0)
License description
Dozvoljavate umnožavanje, distribuciju i javno saopštavanje dela, i prerade, ako se navede ime autora na način odredjen od strane autora ili davaoca licence, čak i u komercijalne svrhe. Ovo je najslobodnija od svih licenci. Osnovni opis Licence: http://creativecommons.org/licenses/by/3.0/rs/deed.sr_LATN Sadržaj ugovora u celini: http://creativecommons.org/licenses/by/3.0/rs/legalcode.sr-Latn
Language
Serbian
Cobiss-ID
Inventory ID
050003529
Theses Type
Doktorska disertacija
description
Datum odbrane: 01.04.2022.
Other responsibilities
Academic Expertise
Medicinske nauke
University
Univerzitet u Kragujevcu
Faculty
Fakultet medicinskih nauka
Alternative title
Significance of epithelial-mesenchymal transition in colorectal cancerogenesis
Publisher
[B. G. Ranković]
Format
70 listova
Abstract (en)
ABSTRACT:
The development of colorectal carcinoma (CRC) is divided in several stages, from normal
mucosa to adenoma and invasive carcinoma. In routine diagnostic work, the correct diagnosis
of colorectal adenoma, adenoma with epithelial misplacement and CRC is of utmost
importance, enabling to choose the optimal treatment. Endoscopic removal is the treatment
of choice for adenomas and adenomas with epithelial misplacement, since these lesions do
not metastasize and additional surgical treatment is not necessary. In contrast, CRC including
early stages (malignant adenomas) are capable to metastasize. It is important to make the
correct diagnosis and to evaluate the risk for metastases and additionally treat these patients
with surgical removal of the colon if needed. Despite meticulous microscopic investigation
of histological slides, it is not always possible to distinguish between various lesions.
Epithelial-mesenchymal transition (EMT) has emerged as a possible mechanism in the
development of CRC, but the information on EMT particularly in early stages of CRC
development is missing. Previous studies have demonstrated some micro RNAs (e.g., miR141, miR-200a/b/c and miR-429) to be good markers of EMT.
Our study included formalin-fixed paraffin-embedded biopsy samples of 62 patients (10
adenomas and 30 cases of CRC with corresponding normal mucosa, 10 malignant adenomas,
and 12 adenomas with pseudoinvasion). Expression of miR-141, miR-200a/b/c and miR-429
and their target genes (CDKN1B, ONECUT2, PTPN13, RND3, SOX2, TGFB2 and ZEB2) was
analysed using quantitative real-time PCR. Expression of E-cadherin was analysed using
immunohistochemistry.
All miRNAs were down-regulated and their target genes showed the opposite expression in
CRC compared to adenoma. Down-regulation of the miR-200 family at the invasive front in
comparison to the central part of tumour was observed as well as a correlation of expression
of the miR200b, CDKN1B, ONECUT2 and ZEB2 to nodal metastases. Expression of the miR200 family and SOX2 also correlated with E-cadherin staining. In addition, down-regulation
of the miR-200 family and PTPN13 and upregulation of CDKN1B in early carcinoma
compared to adenomas and adenomas with epithelial misplacement was observed.
These results suggest that the miR-200 family and their target genes contribute to progression
of adenoma to CRC, invasive properties and development of metastases. Our results strongly
support the postulated hypotheses of partial EMT and intra-tumour heterogeneity during CRC
cancerogenesis.
Authors Key words
кolorektalni karcinom, epitelno-mezenhimalna tranzicija, ciljani geni
Authors Key words
colorectal adenoma, colorectal carcinoma,adenoma with epithelial
misplacement, metastases, intra-tumour heterogeneity, epithelial-mesenchymal transition,
miR-200 family, target genes 4
Classification
616.348-006.6-091.8:577.2(043.3)
Subject
Histopatologija
Type
Tekst
Abstract (en)
ABSTRACT:
The development of colorectal carcinoma (CRC) is divided in several stages, from normal
mucosa to adenoma and invasive carcinoma. In routine diagnostic work, the correct diagnosis
of colorectal adenoma, adenoma with epithelial misplacement and CRC is of utmost
importance, enabling to choose the optimal treatment. Endoscopic removal is the treatment
of choice for adenomas and adenomas with epithelial misplacement, since these lesions do
not metastasize and additional surgical treatment is not necessary. In contrast, CRC including
early stages (malignant adenomas) are capable to metastasize. It is important to make the
correct diagnosis and to evaluate the risk for metastases and additionally treat these patients
with surgical removal of the colon if needed. Despite meticulous microscopic investigation
of histological slides, it is not always possible to distinguish between various lesions.
Epithelial-mesenchymal transition (EMT) has emerged as a possible mechanism in the
development of CRC, but the information on EMT particularly in early stages of CRC
development is missing. Previous studies have demonstrated some micro RNAs (e.g., miR141, miR-200a/b/c and miR-429) to be good markers of EMT.
Our study included formalin-fixed paraffin-embedded biopsy samples of 62 patients (10
adenomas and 30 cases of CRC with corresponding normal mucosa, 10 malignant adenomas,
and 12 adenomas with pseudoinvasion). Expression of miR-141, miR-200a/b/c and miR-429
and their target genes (CDKN1B, ONECUT2, PTPN13, RND3, SOX2, TGFB2 and ZEB2) was
analysed using quantitative real-time PCR. Expression of E-cadherin was analysed using
immunohistochemistry.
All miRNAs were down-regulated and their target genes showed the opposite expression in
CRC compared to adenoma. Down-regulation of the miR-200 family at the invasive front in
comparison to the central part of tumour was observed as well as a correlation of expression
of the miR200b, CDKN1B, ONECUT2 and ZEB2 to nodal metastases. Expression of the miR200 family and SOX2 also correlated with E-cadherin staining. In addition, down-regulation
of the miR-200 family and PTPN13 and upregulation of CDKN1B in early carcinoma
compared to adenomas and adenomas with epithelial misplacement was observed.
These results suggest that the miR-200 family and their target genes contribute to progression
of adenoma to CRC, invasive properties and development of metastases. Our results strongly
support the postulated hypotheses of partial EMT and intra-tumour heterogeneity during CRC
cancerogenesis.
“Data exchange” service offers individual users metadata transfer in several different formats. Citation formats are offered for transfers in texts as for the transfer into internet pages. Citation formats include permanent links that guarantee access to cited sources. For use are commonly structured metadata schemes : Dublin Core xml and ETUB-MS xml, local adaptation of international ETD-MS scheme intended for use in academic documents.
