KRT17 as a prognostic biomarker for stage II colorectal cancer.
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Biomarkers, Tumor
/ genetics
Chemotherapy, Adjuvant
Colorectal Neoplasms
/ drug therapy
Female
Follow-Up Studies
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Keratin-17
/ genetics
Male
Neoplasm Recurrence, Local
/ drug therapy
Neoplasm Staging
Retrospective Studies
Survival Rate
Transcriptome
Tumor Cells, Cultured
Journal
Carcinogenesis
ISSN: 1460-2180
Titre abrégé: Carcinogenesis
Pays: England
ID NLM: 8008055
Informations de publication
Date de publication:
10 07 2020
10 07 2020
Historique:
received:
30
05
2019
revised:
15
10
2019
accepted:
20
11
2019
pubmed:
23
11
2019
medline:
28
10
2020
entrez:
23
11
2019
Statut:
ppublish
Résumé
Adjuvant chemotherapy is considered for patients with stage II colorectal cancer (CRC) characterized by poor prognostic clinicopathological features; however, current stratification algorithms remain inadequate for identifying high-risk patients. To develop prognostic assays, we conducted a step-wise screening and validation strategy using nine cohorts of stage II patients based on multiple platforms, including microarray, RNA-sequencing (RNA-seq) and immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) tissues. Four microarray datasets (total n = 458) were used as the discovery set to screen for single genes associated with postoperative recurrence. Prognostic values of candidate genes were evaluated in three independent microarray/RNA-seq validation cohorts (n = 89, n = 93 and n = 183, respectively), and then IHC for KRT17 was conducted in two independent FFPE series (n = 110 and n = 44, respectively). We found that high levels of KRT17 transcript expression were significantly associated with poor relapse-free survival (RFS) not only in the discovery set, but also in three validation cohorts, and its prognostic impact was independent of conventional factors by multivariate analyses. Positive staining of KRT17 protein was significantly associated with poor RFS in two independent FFPE cohorts. KRT17 protein expression had independent prognostic impact on RFS in a multivariate model adjusted for conventional variables, including high-risk clinicopathological features. In conclusion, using nine independent cohorts consisting of 997 stage II patients, we identified and validated the expression of KRT17 transcript and KRT17 protein as a robust prognostic biomarker that can discriminate postoperative stage II patients who are at high probability of disease recurrence, providing additional prognostic stratification beyond the currently available high-risk factors.
Identifiants
pubmed: 31754689
pii: 5637557
doi: 10.1093/carcin/bgz192
doi:
Substances chimiques
Biomarkers, Tumor
0
KRT17 protein, human
0
Keratin-17
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
591-599Informations de copyright
© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.