How else can we approach prostate cancer biomarker discovery?

Drake, Richard; Angel, Peggi; Wu, Jennifer D.; Pachynski, Russell K.; Ippolito, Joseph E.

doi:10.1080/14737159.2019.1665507

Cited by 9 publications

(5 citation statements)

References 13 publications

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“…However, FFPE limits functional and molecular analysis of tumor microenvironment that have shown promise in identifying new prognostic and predictive biomarkers. [25][26][27][28][29] When evaluating clinical cases, we found the vast majority, in fact 100% of Gleason Grade Group (GGG) 3+ cases, discarded excess tissue not needed for pathologic diagnosis due to the high volume of tumor in these patients.…”

Section: Discussionmentioning

confidence: 99%

Fresh tissue procurement and preparation for multicompartment and multimodal analysis of the prostate tumor microenvironment

et al. 2022

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Background: Prostatic cancers include a diverse microenvironment of tumor cells, cancer-associated fibroblasts, and immune components. This tumor microenvironment (TME) is a known driving force of tumor survival after treatment, but the standard-of-care tissue freezing or fixation in pathology practice limit the use of available approaches/tools to study the TME's functionality in tumor resistance. Thus, there is a need for approaches that satisfy both clinical and laboratory endpoints for TME study. Here we present methods for clinical case identification, tissue processing, and analytical workflow that are compatible with standard histopathology while enabling molecular and functional interrogation of prostate TME components. Methods:We first performed a small retrospective review to identify cases where submission of alternate prostate tissue slices and a parallel live tissue processing protocol complement traditional histopathology and enable viable multicompartment analysis of the TME. Then, we tested its compatibility with commonly employed methods to study the microenvironment including quantification of components both in situ and after tissue dissociation. We also evaluated tissue digestion conditions and cell isolation techniques to aid various molecular and functional endpoints.Results: We identified Gleason Grade Group 3+ clinical cases where tumor volume was sufficient to allow slicing of unfixed tissue and distribution of alternating tissue slices to standard-of-care histopathology and viable multi-modal TME analyses. No single method was found that preserved cellular sub-types for all downstream readouts; instead, tissues were further divided so techniques could be catered to each endpoint. For instance, we show that incorporating the protease dispase into tissue dissociation improves viability for culture and functional analyses but hinders immune cell analysis by flow cytometry. We also found that flow activated cell sorting provides highly pure cell populations for quantitative reverse-transcription polymerase chain reaction and RNA-seq while isolation using antibody-labeled paramagnetic particles facilitated functional coculture experiments.

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Section: Discussionmentioning

confidence: 99%

Fresh tissue procurement and preparation for multicompartment and multimodal analysis of the prostate tumor microenvironment

et al. 2022

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“…N‐glycan IMS is amenable to multiplexing with immunohistochemical and immunofluorescence imaging, generating multi‐modal data for both glycan and protein markers of interest which has demonstrated utility in the characterization of disease states (Clif et al, 2020b; Levenson et al, 2015; McDowell et al, 2020; Tan et al, 2020; Yagnik et al, 2021). Linkage of N‐glycan IMS with more advanced molecular imaging modalities like mass cytometry/mibiTOF (Keren et al, 2019), and in the other resolution direction, clinical MRI combinations are being pursued (Abdelmoula et al, 2019; Basu & Agar, 2021; Drake et al, 2020a).…”

Section: Discussionmentioning

confidence: 99%

Applications and continued evolution of glycan imaging mass spectrometry

McDowell

Mehta

et al. 2021

Mass Spectrometry Reviews

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Glycosylation is an important posttranslational modifier of proteins and lipid conjugates critical for the stability and function of these macromolecules. Particularly important are N‐linked glycans attached to asparagine residues in proteins. N‐glycans have well‐defined roles in protein folding, cellular trafficking and signal transduction, and alterations to them are implicated in a variety of diseases. However, the non‐template driven biosynthesis of these N‐glycans leads to significant structural diversity, making it challenging to identify the most biologically and clinically relevant species using conventional analyses. Advances in mass spectrometry instrumentation and data acquisition, as well as in enzymatic and chemical sample preparation strategies, have positioned mass spectrometry approaches as powerful analytical tools for the characterization of glycosylation in health and disease. Imaging mass spectrometry expands upon these strategies by capturing the spatial component of a glycan's distribution in‐situ, lending additional insight into the organization and function of these molecules. Herein we review the ongoing evolution of glycan imaging mass spectrometry beginning with widely adopted tissue imaging approaches and expanding to other matrices and sample types with potential research and clinical implications. Adaptations of these techniques, along with their applications to various states of disease, are discussed. Collectively, glycan imaging mass spectrometry analyses broaden our understanding of the biological and clinical relevance of N‐glycosylation to human disease.

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“…To minimise the overdiagnosis and overtreatment associated with the current PSA-based diagnostic tests, there is an acknowledged need for prognostic clinical and molecular biomarkers to be incorporated in the diagnosis of PCa [ 4 , 15 ]. Omics (e.g., genomics, transcriptomics, lipidomics, proteomics, epigenomics)-based research has played a very important role in discovering novel targets and putative biomarkers for prostate and other cancers.…”

Section: Rewired Lipid Metabolism As a Source Of Biomarkers And Thera...mentioning

confidence: 99%

Unravelling Prostate Cancer Heterogeneity Using Spatial Approaches to Lipidomics and Transcriptomics

Mutuku

Spotbeen

Trim

et al. 2022

Cancers

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Due to advances in the detection and management of prostate cancer over the past 20 years, most cases of localised disease are now potentially curable by surgery or radiotherapy, or amenable to active surveillance without treatment. However, this has given rise to a new dilemma for disease management; the inability to distinguish indolent from lethal, aggressive forms of prostate cancer, leading to substantial overtreatment of some patients and delayed intervention for others. Driving this uncertainty is the critical deficit of novel targets for systemic therapy and of validated biomarkers that can inform treatment decision-making and to select and monitor therapy. In part, this lack of progress reflects the inherent challenge of undertaking target and biomarker discovery in clinical prostate tumours, which are cellularly heterogeneous and multifocal, necessitating the use of spatial analytical approaches. In this review, the principles of mass spectrometry-based lipid imaging and complementary gene-based spatial omics technologies, their application to prostate cancer and recent advancements in these technologies are considered. We put in perspective studies that describe spatially-resolved lipid maps and metabolic genes that are associated with prostate tumours compared to benign tissue and increased risk of disease progression, with the aim of evaluating the future implementation of spatial lipidomics and complementary transcriptomics for prognostication, target identification and treatment decision-making for prostate cancer.

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How else can we approach prostate cancer biomarker discovery?

Cited by 9 publications

References 13 publications

Fresh tissue procurement and preparation for multicompartment and multimodal analysis of the prostate tumor microenvironment

Fresh tissue procurement and preparation for multicompartment and multimodal analysis of the prostate tumor microenvironment

Applications and continued evolution of glycan imaging mass spectrometry

Unravelling Prostate Cancer Heterogeneity Using Spatial Approaches to Lipidomics and Transcriptomics

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