PhD Scientific Days 2022

Molecular Sciences IV.

Functional Study of Intratumoral Cellular Heterogeneity for Consensus Molecular Subtypes in Colorectal Cancer

Előadó neve

Carmi, Idan

Előadó munkahelye

Genetics Cell and Immunobiology Department of Semmelweis University

Előadó telefonszáma

+36304805070

Előadó e-mail címe

idan.carmi@gmail.com

Az előadás címe

Functional Study of Intratumoral Cellular Heterogeneity for Consensus Molecular Subtypes in Colorectal Cancer

Szerző(k) neve és munkahelye

Idan Carmi1, Zoltan Wiener1

Semmelweis University, Department of Genetics Cell and Immunobiology, Molecular Cancer Research Group

Bemutatás módja

Szóbeli

Szekció

Molecular Sciences IV.

Language of the presentation

English

Preferred session

Pathology and Oncology

Összefoglaló szövege

Colorectal cancer (CRC) is a prevalent cause of cancer-related mortality. Organoid technology retains cellular and molecular heterogeneity of the original tissue. Consensus Molecular Subtyping is a pathogenetic classification system recognizing four subtypes of CRC (CMS1-4). CMS2 and CMS3 contain the classical CRC tubulovillous adenoma development with APC and/or KRAS mutations, respectively. CMS4 is characterized by its epithelial-mesenchymal transition and fibroblast accumulation and has the worst prognosis. The relevant suggested markers for CMS2/3 are CDX2, and for CMS4 HTR2B, FRMD6, and ZEB1 for immunohistochemical evaluation.

To study the expression patterns and the overlaps of CMS2/3 and CMS4 markers in CRC patient-derived organoids (PDO), and understand their functional significance
To prove the intratumoral heterogeneity of CMS4 markers in organoids and patient-derived tissue samples
To identify CRC cells with distinct expression levels of these markers

Primary CRC samples were used to culture PDOs. We studied biomarker (FRMD6, ZEB1, HTR2B, CDX2) heterogeneity, and cellular proliferation (KI67) with immunohistochemisty. With fluorescence-activated cell sorting CRC subpopulations with high and low levels of HTR2B were separated. Organoid diameters were measured with light microscopy.

HTR2B had the highest intratumoral heterogeneity amongst markers for CMS4 in PDOs. There was only a minor overlap between the expression pattern of HTR2B and the CMS2/3 marker CDX2. We proved the heterogeneity of HTR2B in CRC tissue sections, too. Sorted HTR2Blow and HTR2Bhigh CRC cells maintained the expression difference pattern after 7 days. We observed larger diameters with more KI67+ cells in the HTR2Bhigh subpopulation compared to organoids derived from HTR2Blow cells.

We detected heterogeneity for levels of CDX2 and HTR2B and these molecules marked distinct populations within the organoids. CRC cell populations with different levels of CMS4 markers have differing proliferation intensity. Thus, heterogeneity of these biomarkers may influence categorization of CRC patients.

OTKA137554 (Z.W.), TKP2021-EGA-24, ÚNKP New National Excellence Program (ÚNKP-21-5-SE-16 for ZW and ÚNKP-21-2-SE-16 for IC, Ministry of Innovation and Technology), János Bolyai Research Fellowship (BO/00131/20/8, Hungarian Academy of Sciences, ZW)

University and Doctoral School

Semmelweis University, Doctoral School of Molecular Medicine

Supervisor

Dr. Zoltan Wiener

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6429

Start

16:00

End

16:15

Authors (legacy)

Idan Carmi1, Zoltan Wiener1

Semmelweis University, Department of Genetics Cell and Immunobiology, Molecular Cancer Research Group