Molecular subtyping improves prognostication of Stage 2 colorectal cancer.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Colorectal Neoplasms
/ diagnosis
Computational Biology
/ methods
Female
Gene Expression Profiling
/ methods
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Staging
Postoperative Care
Prognosis
Proportional Hazards Models
Recurrence
Transcriptome
Colorectal cancer
Gene expression
Molecular classification
Prognostication
Staging
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
27 Nov 2019
27 Nov 2019
Historique:
received:
21
08
2019
accepted:
04
11
2019
entrez:
29
11
2019
pubmed:
30
11
2019
medline:
4
4
2020
Statut:
epublish
Résumé
Post-surgical staging is the mainstay of prognostic stratification for colorectal cancer (CRC). Here, we compare TNM staging to consensus molecular subtyping (CMS) and assess the value of subtyping in addition to stratification by TNM. Three hundred and eight treatment-naïve colorectal tumours were accessed from our institutional tissue bank. CMS typing was carried out using tumour gene-expression data. Post-surgical TNM-staging and CMS were analysed with respect to clinicopathologic variables and patient outcome. CMS alone was not associated with survival, while TNM stage significantly explained mortality. Addition of CMS to TNM-stratified tumours showed a prognostic effect in stage 2 tumours; CMS3 tumours had a significantly lower overall survival (P = 0.006). Stage 2 patients with a good prognosis showed immune activation and up-regulation of tumour suppressor genes. Although stratification using CMS does not outperform TNM staging as a prognostic indicator, gene-expression based subtyping shows promise for improved prognostication in stage 2 CRC.
Sections du résumé
BACKGROUND
BACKGROUND
Post-surgical staging is the mainstay of prognostic stratification for colorectal cancer (CRC). Here, we compare TNM staging to consensus molecular subtyping (CMS) and assess the value of subtyping in addition to stratification by TNM.
METHODS
METHODS
Three hundred and eight treatment-naïve colorectal tumours were accessed from our institutional tissue bank. CMS typing was carried out using tumour gene-expression data. Post-surgical TNM-staging and CMS were analysed with respect to clinicopathologic variables and patient outcome.
RESULTS
RESULTS
CMS alone was not associated with survival, while TNM stage significantly explained mortality. Addition of CMS to TNM-stratified tumours showed a prognostic effect in stage 2 tumours; CMS3 tumours had a significantly lower overall survival (P = 0.006). Stage 2 patients with a good prognosis showed immune activation and up-regulation of tumour suppressor genes.
CONCLUSIONS
CONCLUSIONS
Although stratification using CMS does not outperform TNM staging as a prognostic indicator, gene-expression based subtyping shows promise for improved prognostication in stage 2 CRC.
Identifiants
pubmed: 31775679
doi: 10.1186/s12885-019-6327-4
pii: 10.1186/s12885-019-6327-4
pmc: PMC6882162
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1155Références
Cancer Treat Rev. 2017 Jun;57:1-7
pubmed: 28505475
Mol Oncol. 2018 Jan;12(1):132-147
pubmed: 29130628
Nat Med. 2015 Nov;21(11):1350-6
pubmed: 26457759
Clin Cancer Res. 2007 Nov 15;13(22 Pt 2):6862s-70s
pubmed: 18006791
Cancer Epidemiol. 2015 Oct;39(5):734-44
pubmed: 26277328
J Clin Oncol. 2011 Jan 1;29(1):17-24
pubmed: 21098318
Genome Med. 2017 May 24;9(1):46
pubmed: 28539123
Arch Pathol Lab Med. 2017 May;141(5):625-657
pubmed: 28165284
Gut. 2009 Jan;58(1):90-6
pubmed: 18832519
Sci Rep. 2016 Jul 15;6:29765
pubmed: 27416752
J Clin Oncol. 2019 Aug 1;37(22):1876-1885
pubmed: 31042420
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Ann Oncol. 2018 Nov 1;29(11):2240-2246
pubmed: 30247524
BMC Bioinformatics. 2010 Sep 27;11:485
pubmed: 20875133
Histopathology. 2007 Jan;50(1):113-30
pubmed: 17204026
Pharmacol Ther. 2015 Jun;150:33-46
pubmed: 25595324
Ann Oncol. 2018 May 1;29(5):1227-1234
pubmed: 29518181
Behav Brain Res. 2001 Nov 1;125(1-2):279-84
pubmed: 11682119
Clin Cancer Res. 2015 Dec 1;21(23):5294-304
pubmed: 26187617
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
J Pathol. 2013 Feb;229(3):441-8
pubmed: 23165447
Nat Genet. 2017 May;49(5):708-718
pubmed: 28319088
Oncogenesis. 2017 Jul 10;6(7):e357
pubmed: 28692036
Cancer Discov. 2015 Jan;5(1):16-8
pubmed: 25583798
Nature. 2012 Jul 18;487(7407):330-7
pubmed: 22810696
Clin Cancer Res. 2016 Aug 15;22(16):4095-104
pubmed: 27151745
Crit Rev Oncol Hematol. 2017 Jan;109:9-19
pubmed: 28010901
Sci Rep. 2017 Sep 14;7(1):11590
pubmed: 28912574
Semin Cancer Biol. 2019 Apr;55:37-52
pubmed: 29775690
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
Clin Gastroenterol Hepatol. 2019 Feb;17(3):402-410.e2
pubmed: 29306042
Cancers (Basel). 2011 Jun 23;3(2):2767-810
pubmed: 24212832
Gastroenterology. 2010 Jun;138(6):2088-100
pubmed: 20420948
Ann Oncol. 2017 May 1;28(5):1023-1031
pubmed: 28453697