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. 2018 Nov 12;13(11):e0206475.
doi: 10.1371/journal.pone.0206475. eCollection 2018.

Novel protein signatures suggest progression to muscular invasiveness in bladder cancer

Magnus Berle  1   2   3 , Luiza Ghila  4   5 , Heidrun Vethe  4   5 , Adeel Chaudhry  1   3 , Hilde Garberg  6 , Christian Beisland  1   3 , Øystein Ariansen Haaland  7 , Eystein Oveland  6 , Ole Johan Halvorsen  8   9 , Thomas Davidsson  1   3 , Simona Chera  4   5
Affiliations

Novel protein signatures suggest progression to muscular invasiveness in bladder cancer

Magnus Berle et al. PLoS One. .

Abstract

Patients with bladder cancer need frequent controls over long follow-up time due to high recurrence rate and risk of conversion to muscle invasive cancer with poor prognosis. We identified cancer-related molecular signatures in apparently healthy bladder in patients with subsequent muscular invasiveness during follow-up. Global proteomics of the normal tissue biopsies revealed specific proteome fingerprints in these patients prior to subsequent muscular invasiveness. In these presumed normal samples, we detected modulations of proteins previously associated with different cancer types. This study indicates that analyzing apparently healthy tissue of a cancer-invaded organ may suggest disease progression.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Global proteomics of eight NMIBC patients reveals outliers.
a) Cartoon depicting the bladder and the generic location of the biopsies prelevation for proteomics (T = tumor, N = normal). b) PC plot of tumor biopsies “T” and normal bladder “N” from eight patients and six quality control samples. c) Hierarchical clustering with heat map show a separation between tumor biopsies “T”, normal biopsies “N” and illustrate outliers T3, N1 and N8. d) Scheme depicting the time evolution of the outliers (red letters) and typical patients patients (green–NMIBC, purple–MIBC Δt—time interval). e) KEGG pathway of bladder cancer; red marks annotation of proteins identified to genes with known involvement in bladder cancer.
Fig 2
Fig 2. Global proteome analysis of the outliers (N1&N8) and control samples (N2 to N7).
a) Scheme depicting the experimental design of the proteome comparison strategy. b) Table of upstream regulators predicted to be responsible for the deregulated proteomic fingerprint observed in the outlier samples. c) A graphical representation of previously described bladder cancer markers of tumor and control tissue with standard error of mean.
Fig 3
Fig 3. Global proteome analysis of similarities between the outlier and tumor samples.
a) Scheme depicting the experimental design of the proteome comparison strategy. b) Table of the predicted upstream regulators responsible for the deregulated proteomic fingerprint observed in the outlier samples. c) Table of the canonical pathways revealed by the pathway analysis in the analyzed DE protein list.
Fig 4
Fig 4. Global proteome analysis of “outlier-specific” molecular signature.
a) Experimental design of the proteome comparison strategy. b) Table of the predicted upstream regulators. c) Table of the canonical pathways.
See this image and copyright information in PMC

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