Molecular portraits of colorectal cancer morphological regions

J 2023

Molecular portraits of colorectal cancer morphological regions

BUDINSKÁ, Eva; Martina HRIVŇÁKOVÁ; Tina CATELA IVKOVIĆ; Marie BOUDNÁ; Rudolf NENUTIL et al.

Základní údaje

Originální název

Molecular portraits of colorectal cancer morphological regions

Autoři

Vydání

eLife, CAMBRIDGE, ELIFE SCIENCES PUBL LTD, 2023, 2050-084X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.400

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/23:00132477

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

cancer biology; colorectal cancer; human; intra-tumor heterogeneity; morphology; transcriptomics

Štítky

14110513, 14110516, 143180, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 3. 2024 14:44, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

Heterogeneity of colorectal carcinoma (CRC) represents a major hurdle towards personalized medicine. Efforts based on whole tumor profiling demonstrated that the CRC molecular subtypes were associated with specific tumor morphological patterns representing tumor subregions. We hypothesize that whole-tumor molecular descriptors depend on the morphological heterogeneity with significant impact on current molecular predictors. We investigated intra-tumor heterogeneity by morphology-guided transcriptomics to better understand the links between gene expression and tumor morphology represented by six morphological patterns (morphotypes): complex tubular, desmoplastic, mucinous, papillary, serrated, and solid/trabecular. Whole-transcriptome profiling by microarrays of 202 tumor regions (morphotypes, tumor-adjacent normal tissue, supportive stroma, and matched whole tumors) from 111 stage II-IV CRCs identified morphotype-specific gene expression profiles and molecular programs and differences in their cellular buildup. The proportion of cell types (fibroblasts, epithelial and immune cells) and differentiation of epithelial cells were the main drivers of the observed disparities with activation of EMT and TNF-α signaling in contrast to MYC and E2F targets signaling, defining major gradients of changes at molecular level. Several gene expression-based (including single-cell) classifiers, prognostic and predictive signatures were examined to study their behavior across morphotypes. Most exhibited important morphotype-dependent variability within same tumor sections, with regional predictions often contradicting the whole-tumor classification. The results show that morphotype-based tumor sampling allows the detection of molecular features that would otherwise be distilled in whole tumor profile, while maintaining histopathology context for their interpretation. This represents a practical approach at improving the reproducibility of expression profiling and, by consequence, of gene-based classifiers.

Návaznosti

EF15_003/0000469, projekt VaV

Název: Cetocoen Plus

EF17_043/0009632, projekt VaV

Název: CETOCOEN Excellence

GA19-08646S, projekt VaV

Název: Molekulární portréty hlavních morfologických komponent nádorů kolorekta

Investor: Grantová agentura ČR, Molecular portraits of major morphological components of colon tumors

LM2018121, projekt VaV

Název: Výzkumná infrastruktura RECETOX (Akronym: RECETOX RI)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, RECETOX RI

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

857560, interní kód MU
(Kód CEP: EF17_043/0009632)

Název: CETOCOEN Excellence (Akronym: CETOCOEN Excellence)

Investor: Evropská unie, CETOCOEN Excellence, Spreading excellence and widening participation

Přiložené soubory

Molecular_portraits_of_colorectal_cancer_morphological_regions.pdf

Citovat

BUDINSKÁ, Eva; Martina HRIVŇÁKOVÁ; Tina CATELA IVKOVIĆ; Marie BOUDNÁ; Rudolf NENUTIL; Beatrix BENCSIKOVÁ; Dagmar AL TUKMACHI; Michaela RUČKOVÁ; Lenka DUBSKÁ; Ondřej SLABÝ; Josef FEIT; Dragomir MIHNEA-PAUL; Petra BOŘILOVÁ LINHARTOVÁ; Sabine TEJPAR a Vlad POPOVICI. Molecular portraits of colorectal cancer morphological regions. eLife. CAMBRIDGE: ELIFE SCIENCES PUBL LTD, 2023, roč. 12, Nov, s. 1-20. ISSN 2050-084X. Dostupné z: https://doi.org/10.7554/eLife.86655.3.

@article{2348537,
   author = {Budinská, Eva and Hrivňáková, Martina and Catela Ivković, Tina and Boudná, Marie and Nenutil, Rudolf and Bencsiková, Beatrix and Al Tukmachi, Dagmar and Ručková, Michaela and Dubská, Lenka and Slabý, Ondřej and Feit, Josef and MihneaandPaul, Dragomir and Bořilová Linhartová, Petra and Tejpar, Sabine and Popovici, Vlad},
   article_location = {CAMBRIDGE},
   article_number = {Nov},
   doi = {https://doi.org/10.7554/eLife.86655.3},
   keywords = {cancer biology; colorectal cancer; human; intra-tumor heterogeneity; morphology; transcriptomics},
   language = {eng},
   issn = {2050-084X},
   journal = {eLife},
   title = {Molecular portraits of colorectal cancer morphological regions},
   url = {https://elifesciences.org/articles/86655},
   volume = {12},
   year = {2023}
}

TY  - JOUR
ID  - 2348537
AU  - Budinská, Eva - Hrivňáková, Martina - Catela Ivković, Tina - Boudná, Marie - Nenutil, Rudolf - Bencsiková, Beatrix - Al Tukmachi, Dagmar - Ručková, Michaela - Dubská, Lenka - Slabý, Ondřej - Feit, Josef - Mihnea-Paul, Dragomir - Bořilová Linhartová, Petra - Tejpar, Sabine - Popovici, Vlad
PY  - 2023
TI  - Molecular portraits of colorectal cancer morphological regions
JF  - eLife
VL  - 12
IS  - Nov
SP  - 1-20
EP  - 1-20
PB  - ELIFE SCIENCES PUBL LTD
SN  - 2050084X
KW  - cancer biology
KW  - colorectal cancer
KW  - human
KW  - intra-tumor heterogeneity
KW  - morphology
KW  - transcriptomics
UR  - https://elifesciences.org/articles/86655
N2  - Heterogeneity of colorectal carcinoma (CRC) represents a major hurdle towards personalized medicine. Efforts based on whole tumor profiling demonstrated that the CRC molecular subtypes were associated with specific tumor morphological patterns representing tumor subregions. We hypothesize that whole-tumor molecular descriptors depend on the morphological heterogeneity with significant impact on current molecular predictors. We investigated intra-tumor heterogeneity by morphology-guided transcriptomics to better understand the links between gene expression and tumor morphology represented by six morphological patterns (morphotypes): complex tubular, desmoplastic, mucinous, papillary, serrated, and solid/trabecular. Whole-transcriptome profiling by microarrays of 202 tumor regions (morphotypes, tumor-adjacent normal tissue, supportive stroma, and matched whole tumors) from 111 stage II-IV CRCs identified morphotype-specific gene expression profiles and molecular programs and differences in their cellular buildup. The proportion of cell types (fibroblasts, epithelial and immune cells) and differentiation of epithelial cells were the main drivers of the observed disparities with activation of EMT and TNF-α signaling in contrast to MYC and E2F targets signaling, defining major gradients of changes at molecular level. Several gene expression-based (including single-cell) classifiers, prognostic and predictive signatures were examined to study their behavior across morphotypes. Most exhibited important morphotype-dependent variability within same tumor sections, with regional predictions often contradicting the whole-tumor classification. The results show that morphotype-based tumor sampling allows the detection of molecular features that would otherwise be distilled in whole tumor profile, while maintaining histopathology context for their interpretation. This represents a practical approach at improving the reproducibility of expression profiling and, by consequence, of gene-based classifiers.
ER  -

BUDINSKÁ, Eva; Martina HRIVŇÁKOVÁ; Tina CATELA IVKOVI$\backslash$'C; Marie BOUDNÁ; Rudolf NENUTIL; Beatrix BENCSIKOVÁ; Dagmar AL TUKMACHI; Michaela RUČKOVÁ; Lenka DUBSKÁ; Ondřej SLABÝ; Josef FEIT; Dragomir MIHNEA-PAUL; Petra BOŘILOVÁ LINHARTOVÁ; Sabine TEJPAR a Vlad POPOVICI. Molecular portraits of colorectal cancer morphological regions. \textit{eLife}. CAMBRIDGE: ELIFE SCIENCES PUBL LTD, 2023, roč.~12, Nov, s.~1-20. ISSN~2050-084X. Dostupné z: https://doi.org/10.7554/eLife.86655.3.

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