The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
A Composite Gene Expression Signature Optimizes Prediction of Colorectal Cancer Metastasis and Outcome
Open accessPublished version of a preprint
Abstract
Purpose: We previously found that an epithelial-to-mesenchymal transition (EMT)–based gene expression signature was highly correlated with the first principal component (PC1) of 326 colorectal cancer tumors and was prognostic. This study was designed to improve these signatures for better prediction of metastasis and outcome. Experimental Design: A total of 468 colorectal cancer tumors including all stages (I–IV) and metastatic lesions were used to develop a new prognostic score (ΔPC1.EMT) by subtracting the EMT signature score from its correlated PC1 signature score. The score was validated on six other independent datasets with a total of 3,697 tumors. Results: ΔPC1.EMT was found to be far more predictive of metastasis and outcome than its parent scores. It performed well in stages I to III, among microsatellite instability subtypes, and across multiple mutation-based subclasses, demonstrating a refined capacity to predict distant metastatic potential even in tumors with a “good” prognosis. For example, in the PETACC-3 clinical trial dataset, it predicted worse overall survival in an adjusted multivariable model for stage III patients (HR standardized by interquartile range [IQR] = 1.50; 95% confidence interval, 1.25–1.81; P = 0.000016, N = 644). The improved performance of ΔPC1.EMT was related to its propensity to identify epithelial-like subpopulations as well as mesenchymal-like subpopulations. Biologically, the signature was correlated positively with RAS signaling but negatively with mitochondrial metabolism. ΔPC1.EMT was a “best of assessed” prognostic score when compared with 10 other known prognostic signatures. Conclusions: The study developed a prognostic signature score with a propensity to detect non-EMT features, including epithelial cancer stem cell–related properties, thereby improving its potential to predict metastasis and poorer outcome in stage I–III patients. Clin Cancer Res; 22(3); 734–45. ©2015 AACR.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“CRC tumors with activated RAS/RAF pathway appear to be associated with poor outcomes [4].”
From An integrative gene expression signature analysis identifies CMS4 KRAS-mutated colorectal cancers sensitive to combined MEK and SRC targeted therapy (2022) · cites this paper as [4]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Comprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499
limma: Linear Models for Microarray Data
Smyth, G. K. (2005) · Statistics for Biology and Health · doi:10.1007/0-387-29362-0_23 · Cited by 5,796
A Perspective on Cancer Cell Metastasis
Chaffer, C. L., & Weinberg, R. A. (2011) · Science · doi:10.1126/science.1203543 · Cited by 4,905
Greaves, M., & Maley, C. C. (2012) · Nature · doi:10.1038/nature10762 · Cited by 3,162
Marisa, L., de Reyniès, A., Duval, A., Selves, J., Gaub, M. P., Vescovo, L., Etienne-Grimaldi, M.-C., Schiappa, R., Guenot, D., Ayadi, M., et al. (2013) · PLoS Medicine · doi:10.1371/journal.pmed.1001453 · Cited by 1,507
Roth, A. D., Tejpar, S., Delorenzi, M., Yan, P., Fiocca, R., Klingbiel, D., Dietrich, D., Biesmans, B., Bodoky, G., Barone, C., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.3452 · Cited by 1,178
Self-citationLiu, S., Cong, Y., Wang, D., Sun, Y., Deng, L., Liu, Y., Martin-Trevino, R., Li, S., McDermott, S., Landis, M. D., et al. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2013.11.009 · Cited by 1,075
Stromal gene expression defines poor-prognosis subtypes in colorectal cancer
Calon, A., Lonardo, E., Berenguer-Llergo, A., Espinet, E., Hernando-Momblona, X., Iglesias, M., Sevillano, M., Palomo-Ponce, S., Tauriello, D. V. F., Byrom, D., et al. (2015) · Nature Genetics · doi:10.1038/ng.3225 · Cited by 1,070
Slug and Sox9 Cooperatively Determine the Mammary Stem Cell State
Guo, W., Keckesova, Z., Donaher, J. L., Shibue, T., Tischler, V., Reinhardt, F., Itzkovitz, S., Noske, A., Zürrer‐Härdi, U., Bell, G. W., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.008 · Cited by 1,005
Epithelial Plasticity: A Common Theme in Embryonic and Cancer Cells
Nieto, M. A. (2013) · Science · doi:10.1126/science.1234850 · Cited by 991
Flagged first, then by citations
Cited by
Sorted by citations
Lu, Y., Zhao, X., Liu, Q., Li, C., Graves-Deal, R., Cao, Z., Singh, B., Franklin, J. L., Wang, J., Hu, H., et al. (2017) · Nature Medicine · doi:10.1038/nm.4424 · Cited by 425
Self-citationA multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC
Schell, M. J., Yang, M., Teer, J. K., Lo, F. Y., Madan, A., Coppola, D., Monteiro, A. N. A., Nebozhyn, M. V., Yue, B., Loboda, A., et al. (2016) · Nature Communications · doi:10.1038/ncomms11743 · Cited by 207
Self-citationLi, C., Singh, B., Graves-Deal, R., Ma, H., Starchenko, A., Fry, W. H., Lu, Y., Wang, Y., Bogatcheva, G., Khan, M. P., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1618297114 · Cited by 47
Self-citationMLH1 Deficiency Induces Cetuximab Resistance in Colon Cancer via Her‐2/PI3K/AKT Signaling
Han, Y., Peng, Y., Fu, Y., Cai, C., Guo, C., Liu, S., Li, Y., Chen, Y., Shen, E., Long, K., et al. (2020) · Advanced Science · doi:10.1002/advs.202000112 · Cited by 34
Davis, T. B., Yang, M., Schell, M. J., Wang, H., Ma, L., Pledger, W. J., & Yeatman, T. J. (2018) · Scientific Reports · doi:10.1038/s41598-018-27584-x · Cited by 27
Self-citation
Metadata
- Authors
- Schell, M. J., Yang, M., Missiaglia, E., Delorenzi, M., Soneson, C., Yue, B., Nebozhyn, M. V., Loboda, A., Bloom, G., & Yeatman, T. J.
- Affiliations
- Moffitt Cancer Center (US)
- 2Gibbs Cancer Center & Research Institute, Spartanburg, South Carolina.
- SIB Swiss Institute of Bioinformatics (CH)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Schell, Michael J.
- Yeatman, Timothy J.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2016-01-31
- Volume
- 22
- Issue
- 3
- Pages
- 734-745
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC4802496
- OpenAlex
- W2188527201
- Cited by
- 42
- References
- 45
- Citations by year
- 2026: 1 · 2025: 6 · 2023: 1 · 2022: 7 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 2 · 2017: 7 · 2016: 3
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Cancer Institute (U01CA157960, P30CA076292)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Keywords
- colorectal cancer, epithelial-mesenchymal transition, gene expression signatures, metastasis prediction, prognostic score, principal component analysis, cancer stem cells, Ras signaling, mitochondrial metabolism, microsatellite instability, stage III colorectal cancer, overall survival
- MeSH terms
- Female, Humans, Male, Neoplasm Metastasis, Neoplasm Staging, Prognosis, Colorectal Neoplasms, Reproducibility of Results, Gene Expression Regulation, Neoplastic, Cluster Analysis, Proportional Hazards Models, Gene Expression Profiling, Kaplan-Meier Estimate, Microsatellite Instability, Epithelial-Mesenchymal Transition, Transcriptome, Patient Outcome Assessment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
