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|Publication type:||Article in scientific journal|
|Type of review:||Peer review (publication)|
|Title:||Image-based assessment of extracellular mucin-to-tumor area predicts consensus molecular subtypes (CMS) in colorectal cancer|
|Published in:||Modern Pathology|
|Publisher / Ed. Institution:||Nature Publishing Group|
|Subject (DDC):||572: Biochemistry|
|Abstract:||The backbone of all colorectal cancer classifications including the consensus molecular subtypes (CMS) highlights microsatellite instability (MSI) as a key molecular pathway. Although mucinous histology (generally defined as >50% extracellular mucin-to-tumor area) is a "typical" feature of MSI, it is not limited to this subgroup. Here, we investigate the association of CMS classification and mucin-to-tumor area quantified using a deep learning algorithm, and the expression of specific mucins in predicting CMS groups and clinical outcome. A weakly supervised segmentation method was developed to quantify extracellular mucin-to-tumor area in H&E images. Performance was compared to two pathologists' scores, then applied to two cohorts: (1) TCGA (n = 871 slides/412 patients) used for mucin-CMS group correlation and (2) Bern (n = 775 slides/517 patients) for histopathological correlations and next-generation Tissue Microarray construction. TCGA and CPTAC (n = 85 patients) were used to further validate mucin detection and CMS classification by gene and protein expression analysis for MUC2, MUC4, MUC5AC and MUC5B. An excellent inter-observer agreement between pathologists' scores and the algorithm was obtained (ICC = 0.92). In TCGA, mucinous tumors were predominantly CMS1 (25.7%), CMS3 (24.6%) and CMS4 (16.2%). Average mucin in CMS2 was 1.8%, indicating negligible amounts. RNA and protein expression of MUC2, MUC4, MUC5AC and MUC5B were low-to-absent in CMS2. MUC5AC protein expression correlated with aggressive tumor features (e.g., distant metastases (p = 0.0334), BRAF mutation (p < 0.0001), mismatch repair-deficiency (p < 0.0001), and unfavorable 5-year overall survival (44% versus 65% for positive/negative staining). MUC2 expression showed the opposite trend, correlating with less lymphatic (p = 0.0096) and venous vessel invasion (p = 0.0023), no impact on survival.The absence of mucin-expressing tumors in CMS2 provides an important phenotype-genotype correlation. Together with MSI, mucinous histology may help predict CMS classification using only histopathology and should be considered in future image classifiers of molecular subtypes.|
|Fulltext version:||Published version|
|License (according to publishing contract):||CC BY 4.0: Attribution 4.0 International|
|Departement:||Life Sciences and Facility Management|
|Organisational Unit:||Institute of Computational Life Sciences (ICLS)|
|Published as part of the ZHAW project:||Trans-omic approach to colorectal cancer: an integrative computational and clinical perspective|
|Appears in collections:||Publikationen Life Sciences und Facility Management|
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|2021_Nguyen-etal_CMS-prediction-colorectal-cancer.pdf||2.24 MB||Adobe PDF|
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Nguyen, H.-G., Lundström, O., Blank, A., Dawson, H., Lugli, A., Anisimova, M., & Zlobec, I. (2021). Image-based assessment of extracellular mucin-to-tumor area predicts consensus molecular subtypes (CMS) in colorectal cancer. Modern Pathology, 35, 240–248. https://doi.org/10.1038/s41379-021-00894-8
Nguyen, H.-G. et al. (2021) ‘Image-based assessment of extracellular mucin-to-tumor area predicts consensus molecular subtypes (CMS) in colorectal cancer’, Modern Pathology, 35, pp. 240–248. Available at: https://doi.org/10.1038/s41379-021-00894-8.
H.-G. Nguyen et al., “Image-based assessment of extracellular mucin-to-tumor area predicts consensus molecular subtypes (CMS) in colorectal cancer,” Modern Pathology, vol. 35, pp. 240–248, Sep. 2021, doi: 10.1038/s41379-021-00894-8.
Nguyen, Huu-Giao, et al. “Image-Based Assessment of Extracellular Mucin-to-Tumor Area Predicts Consensus Molecular Subtypes (CMS) in Colorectal Cancer.” Modern Pathology, vol. 35, Sept. 2021, pp. 240–48, https://doi.org/10.1038/s41379-021-00894-8.
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