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. 2020 Dec;10(8):e199.
doi: 10.1002/ctm2.199.

Multicohort and cross-platform validation of a prognostic Wnt signature in colorectal cancer

Affiliations

Multicohort and cross-platform validation of a prognostic Wnt signature in colorectal cancer

Frauke Goeman et al. Clin Transl Med. 2020 Dec.
No abstract available

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Conflict of interest statement

LP received travel grants from Eisai, Roche, Pfizer, and Novartis and speaker fees from Roche, Pfizer, Novartis, and Gentili. DS received travel grants from Roche, Pharma Mar, and Astra Zeneca and personal fees from Roche. PV received travel grants from Eisai, Roche, Pfizer, and Novartis; speaker fees/advisory boards from Roche, Pfizer, Novartis, and Gentili. RDM declares to be a scientific advisory board member at Exosomics SpA (Siena IT), Hibercell Inc (New York, NY, USA), Kiromic Inc (Houston, TX, USA), and at Exiris Inc (Rome, Italy). The other authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
A, Heatmap showing unsupervised clustering analysis of Wnt genes in the IRE cohort. Targeted DNA‐ and RNA‐Seq were employed to evaluate the mutational status of six Wnt pathway components (APC, CTNNB1, AMER1, TCF7L2, FBXW7, and SOX9) along with the expression of 93 WNT pathway genes. Genes: rows; tissue samples: columns. B, Volcano plot of Wnt genes differently expressed when comparing fast and slow progressors. C, Forest plot illustrating univariate Cox regression analyses for progression‐free survival (PFS). D, Bar charts illustrating the distribution of individual genes in the highest/lowest quartile of overall survival (left) and in responders/non‐responders (right). Transcripts are classified as high and low using the highest tertile as cutoff point. Asterisks indicate statistical significance (univariate Cox regressions in panel C and Chi2 test in panel D) Abbreviations: CR, complete response; OS, overall survival; PD, progressive disease; PR, partial response; SD, stable disease.
FIGURE 2
FIGURE 2
A, Bubble chart illustrating the associations between the Wnt signature and standard clinical‐pathological features of mCRC patients included in the IRE cohort. B, Oncoprint illustrating the distribution of the Wnt signature according to the three different patterns of disease progression. SP: slow progressors (highest quartile of PFS), CP: conventional progressors (intermediate quartiles of PFS), FP: fast progressors (lowest quartile of PFS). Asterisks in panels A and B indicate statistical significance (χ 2, P < .05). C and D, Kaplan‐Meier survival curves of progression‐free survival (PFS) and overall survival (OS) in the IRE cohort
FIGURE 3
FIGURE 3
Kaplan‐Meier survival curves of overall survival (OS) in the TCGA (A), GSE17538 (B), and GSE39582 (C) studies. D, Bar charts illustrating the distribution of the Wnt signature according to the mutational status of APC, TP53, KRAS, PIK3CA, and BRAF in the IRE and TCGA studies. Asterisk indicates statistical significance (χ 2, P < .05)

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