Gene expression patterns unveil a new level of molecular
heterogeneity in colorectal cancer

J 2013

Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer

BUDINSKÁ, Eva, Vlad POPOVICI, Sabine TEJPAR, D Ario GIOVANNI, Nicolas LAPIQUE et. al.

Základní údaje

Originální název

Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer

Autoři

BUDINSKÁ, Eva (703 Slovensko, garant, domácí), Vlad POPOVICI (642 Rumunsko, domácí), Sabine TEJPAR (56 Belgie), D Ario GIOVANNI (756 Švýcarsko), Nicolas LAPIQUE (756 Švýcarsko), Katarzyna Otylia SIKORA (756 Švýcarsko), Antonio Fabio DI NARZO (756 Švýcarsko), Pu YAN (840 Spojené státy), John Graeme HODGSON (756 Švýcarsko), Scott WEINRICH (840 Spojené státy), Fred BOSMAN (840 Spojené státy), Arnaud ROTH (756 Švýcarsko) a Mauro DELORENZI (756 Švýcarsko)

Vydání

JOURNAL OF PATHOLOGY, HOBOKEN, WILEY-BLACKWELL, 2013, 0022-3417

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 7.330

Kód RIV

RIV/00216224:14110/13:00069863

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1002/path.4212

UT WoS

000322761500008

Klíčová slova anglicky

colorectal cancer; histopathology; gene expression; molecular heterogeneity

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 23. 10. 2013 15:22, Soňa Böhmová

Anotace

V originále

The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defined subgroup. We performed a prior free analysis of CRC heterogeneity on 1113 CRC gene expression profiles and confronted our findings to established molecular determinants and clinical, histopathological and survival data. Unsupervised clustering based on gene modules allowed us to distinguish at least five different gene expression CRC subtypes, which we call surface crypt-like, lower crypt-like, CIMP-H-like, mesenchymal and mixed. A gene set enrichment analysis combined with literature search of gene module members identified distinct biological motifs in different subtypes. The subtypes, which were not derived based on outcome, nonetheless showed differences in prognosis. Known gene copy number variations and mutations in key cancer-associated genes differed between subtypes, but the subtypes provided molecular information beyond that contained in these variables. Morphological features significantly differed between subtypes. The objective existence of the subtypes and their clinical and molecular characteristics were validated in an independent set of 720 CRC expression profiles. Our subtypes provide a novel perspective on the heterogeneity of CRC. The proposed subtypes should be further explored retrospectively on existing clinical trial datasets and, when sufficiently robust, be prospectively assessed for clinical relevance in terms of prognosis and treatment response predictive capacity. Original microarray data were uploaded to the ArrayExpress database (http://www.ebi.ac.uk/arrayexpress/) under Accession Nos E-MTAB-990 and E-MTAB-1026.

Citovat

BUDINSKÁ, Eva, Vlad POPOVICI, Sabine TEJPAR, D Ario GIOVANNI, Nicolas LAPIQUE, Katarzyna Otylia SIKORA, Antonio Fabio DI NARZO, Pu YAN, John Graeme HODGSON, Scott WEINRICH, Fred BOSMAN, Arnaud ROTH a Mauro DELORENZI. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer. JOURNAL OF PATHOLOGY. HOBOKEN: WILEY-BLACKWELL, 2013, roč. 231, č. 1, s. 63-76. ISSN 0022-3417. Dostupné z: https://dx.doi.org/10.1002/path.4212.

@article{1126956,
   author = {Budinská, Eva and Popovici, Vlad and Tejpar, Sabine and Giovanni, D Ario and Lapique, Nicolas and Sikora, Katarzyna Otylia and Di Narzo, Antonio Fabio and Yan, Pu and Hodgson, John Graeme and Weinrich, Scott and Bosman, Fred and Roth, Arnaud and Delorenzi, Mauro},
   article_location = {HOBOKEN},
   article_number = {1},
   doi = {http://dx.doi.org/10.1002/path.4212},
   keywords = {colorectal cancer; histopathology; gene expression; molecular heterogeneity},
   language = {eng},
   issn = {0022-3417},
   journal = {JOURNAL OF PATHOLOGY},
   title = {Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer},
   volume = {231},
   year = {2013}
}

TY  - JOUR
ID  - 1126956
AU  - Budinská, Eva - Popovici, Vlad - Tejpar, Sabine - Giovanni, D Ario - Lapique, Nicolas - Sikora, Katarzyna Otylia - Di Narzo, Antonio Fabio - Yan, Pu - Hodgson, John Graeme - Weinrich, Scott - Bosman, Fred - Roth, Arnaud - Delorenzi, Mauro
PY  - 2013
TI  - Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer
JF  - JOURNAL OF PATHOLOGY
VL  - 231
IS  - 1
SP  - 63-76
EP  - 63-76
PB  - WILEY-BLACKWELL
SN  - 00223417
KW  - colorectal cancer
KW  - histopathology
KW  - gene expression
KW  - molecular heterogeneity
N2  - The recognition that colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behaviour and response to therapy translates into an urgent need for robust molecular disease subclassifiers that can explain this heterogeneity beyond current parameters (MSI, KRAS, BRAF). Attempts to fill this gap are emerging. The Cancer Genome Atlas (TGCA) reported two main CRC groups, based on the incidence and spectrum of mutated genes, and another paper reported an EMT expression signature defined subgroup. We performed a prior free analysis of CRC heterogeneity on 1113 CRC gene expression profiles and confronted our findings to established molecular determinants and clinical, histopathological and survival data. Unsupervised clustering based on gene modules allowed us to distinguish at least five different gene expression CRC subtypes, which we call surface crypt-like, lower crypt-like, CIMP-H-like, mesenchymal and mixed. A gene set enrichment analysis combined with literature search of gene module members identified distinct biological motifs in different subtypes. The subtypes, which were not derived based on outcome, nonetheless showed differences in prognosis. Known gene copy number variations and mutations in key cancer-associated genes differed between subtypes, but the subtypes provided molecular information beyond that contained in these variables. Morphological features significantly differed between subtypes. The objective existence of the subtypes and their clinical and molecular characteristics were validated in an independent set of 720 CRC expression profiles. Our subtypes provide a novel perspective on the heterogeneity of CRC. The proposed subtypes should be further explored retrospectively on existing clinical trial datasets and, when sufficiently robust, be prospectively assessed for clinical relevance in terms of prognosis and treatment response predictive capacity. Original microarray data were uploaded to the ArrayExpress database (http://www.ebi.ac.uk/arrayexpress/) under Accession Nos E-MTAB-990 and E-MTAB-1026.
ER  -

BUDINSKÁ, Eva, Vlad POPOVICI, Sabine TEJPAR, D Ario GIOVANNI, Nicolas LAPIQUE, Katarzyna Otylia SIKORA, Antonio Fabio DI NARZO, Pu YAN, John Graeme HODGSON, Scott WEINRICH, Fred BOSMAN, Arnaud ROTH a Mauro DELORENZI. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer. \textit{JOURNAL OF PATHOLOGY}. HOBOKEN: WILEY-BLACKWELL, 2013, roč.~231, č.~1, s.~63-76. ISSN~0022-3417. Dostupné z: https://dx.doi.org/10.1002/path.4212.

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