Tumour heterogeneity poses a significant challenge to cancer biomarker research

Cyll, Karolina; Ersvær, Elin; Vlatkovic, Ljiljana; Pradhan, Manohar; Kildal, Wanja; Kjær, Marte Avranden; Kleppe, Andreas; Hveem, Tarjei S.; Carlsen, Birgitte; Gill, Silje; Löffeler, Sven; Haug, Erik Skaaheim; Wæhre, Håkon; Sooriakumaran, Prasanna; Danielsen, Håvard E.

doi:10.1038/bjc.2017.171

Cited by 119 publications

(111 citation statements)

References 37 publications

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“…suggested that the intratissue variability is a likely reason for this disappointing discrepancy . The tissue heterogeneity is indeed one of the most recognized challenges for accurate diagnostication and prognostication in PCa …”

Section: Discussionmentioning

confidence: 99%

“…Although grades 2 and 3 have equivalent Gleason sums equal 7, the latter has significantly worse prognosis based on a higher amount of pattern 4 . Although the ISUP grade system has led to more accurate prognostication, the tumor heterogeneity and subjective variations in biopsy sampling and interpretation of the GS still impact the patient outcome and treatment decisions . One of the main goals in PCa research is to discover new molecules to accurately stratify PCa patients with indolent from aggressive tumors.…”

Section: Introductionmentioning

confidence: 99%

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Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia

et al. 2019

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The histology‐based Gleason score (GS) of prostate cancer (PCa) tissue biopsy is the most accurate predictor of disease aggressiveness and an important measure to guide treatment strategies and patient management. The variability associated with PCa tumor sampling and the subjective determination of the GS are challenges that limit accurate diagnostication and prognostication. Thus, novel molecular signatures are needed to distinguish between indolent and aggressive forms of PCa for better patient management and outcomes. Herein, label‐free LC‐MS/MS proteomics is used to profile the proteome of 50 PCa tissues spanning five grade groups (n = 10 per group) relative to tissues from individuals with benign prostatic hyperplasia (BPH). Over 2000 proteins are identified albeit at different levels between and within the patient groups, revealing biological processes associated with specific grades. A panel of 11 prostate‐derived proteins including IGKV3D‐20, RNASET2, TACC2, ANXA7, LMOD1, PRCP, GYG1, NDUFV1, H1FX, APOBEC3C, and CTSZ display the potential to stratify patients from low and high PCa grade groups. Parallel reaction monitoring of the same sample cohort validate the differential expression of LMOD1, GYG1, IGKV3D‐20, and RNASET2. The four proteins associated with low and high PCa grades reported here warrant further exploration as candidate biomarkers for PCa aggressiveness.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia

et al. 2019

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“…A further goal for future work is to explore (and exploit) the heterogeneity of tumor evolution in greater depth: this heterogeneity aids the evasion of the tumor from immune effects. Studying the consequences of decanalization [48] during cancer progression is too-often sidelined, despite evidence supporting its prominence [49–51]. Yet despite these challenges, for which the complexity of the disease may be often in part responsible, great progress has been and continues to be made.…”

Section: Discussionmentioning

confidence: 99%

Modeling the effects of EMT-immune dynamics on epithelial cancer progression

Bergman

Karikomi

et al. 2019

Preprint

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Preceding and during cancer progression, the immune system is engaged in complex sets of interactions with epithelia that affect tumor incidence and prognosis. Inflammation also has significant effects on gastrointestinal and pancreatic tumors. Moreover, epithelial cell plasticity can significantly alter disease trajectories (for better or worse) via epithelial-to-mesenchymal transition (EMT). Several of the same pathways that regulate EMT are involved in tumor-immune interactions, yet little is known about the mechanisms and consequences of these regulatory processes. Here we introduce a multiscale evolutionary model to describe the interplay between tumor-immune-EMT interactions and their impact on epithelial tissues. Through in silico analysis of large patient cohorts, we found controllable regimes that maximize cancer-free survival. Delaying tumorigenesis depended crucially on properties of the mesenchymal phenotype: its growth rate and its immune-evasiveness. We performed analysis of pancreatic cancer data from The Cancer Genome Atlas to compare clinical measurements with model predictions. We found, in broad agreement with the model, that association with EMT worsened the survival probabilities of inflammation-associated cancer. These results offer novel means to delay disease onset by regulating properties of EMT, and demonstrate the importance of studying cancer-immune interactions in light of EMT.

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“…Genomic and transcriptomic analyses have provided insight into the complexity of prostate tumors and the existence of molecular subtypes. However, the clinical applicability of these classifications has been thwarted, due in part to the highly heterogeneous nature of PCa and the difficulty of identifying additional relevant alterations that occur at low frequencies (11)(12)(13)(14)(15)(16)(17)(18) (60). We hypothesized that heterogeneously expressed genes can expose unidentified molecular subclasses of PCa and/or identify translationally relevant gene sets.…”

Section: Discussionmentioning

confidence: 99%

“…The clinical heterogeneity of PCa reflects, in part, a remarkable genomic heterogeneity (11)(12)(13)(14)(15)(16)(17)(18). This suggests that disease stratification based on molecular features may be of prognostic value beyond standard clinicopathological variables, and aid in the clinical management of the disease, as is the case for other cancers, i.e.…”

Section: Introductionmentioning

confidence: 99%