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Assessment of pathological response to therapy using lipid mass spectrometry imaging.

ABSTRACT: In many cancers, the establishment of a patient's future treatment regime often relies on histopathological assessment of tumor tissue specimens in order to determine the extent of the 'pathological response' to a given therapy. However, histopathological assessment of pathological response remains subjective. Here we use MALDI mass spectrometry imaging to generate lipid signatures from colorectal cancer liver metastasis specimens resected from patients preoperatively treated with chemotherapy. Using these signatures we obtained a unique pathological response score that correlates with prognosis. In addition, we identify single lipid moieties that are overexpressed in different histopathological features of the tumor, which have potential as new biomarkers for assessing response to therapy. These data show that computational methods, focusing on the lipidome, can be used to determine prognostic markers for response to chemotherapy and may potentially improve risk assessment and patient care.

SUBMITTER: Patterson NH

PROVIDER: S-EPMC5107952 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Assessment of pathological response to therapy using lipid mass spectrometry imaging.

Patterson Nathan Heath NH Alabdulkarim Balqis B Lazaris Anthoula A Thomas Aurélien A Marcinkiewicz Mieczyslaw M MM Gao Zu-Hua ZH Vermeulen Peter B PB Chaurand Pierre P Metrakos Peter P

Scientific reports 20161114

In many cancers, the establishment of a patient's future treatment regime often relies on histopathological assessment of tumor tissue specimens in order to determine the extent of the 'pathological response' to a given therapy. However, histopathological assessment of pathological response remains subjective. Here we use MALDI mass spectrometry imaging to generate lipid signatures from colorectal cancer liver metastasis specimens resected from patients preoperatively treated with chemotherapy. ...[more]

PMID: 27841360

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Project description:Severe aortic stenosis (AS) is prevalent in adults ≥ 65 years, a significant cause of morbidity and mortality, with no medical therapy. Lipid and proteomic alterations of human AS tissue were determined using mass spectrometry imaging (MSI) and liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to understand histopathology, potential biomarkers of disease, and progression from non-calcified to calcified phenotype. A reproducible MSI method was developed using healthy murine aortic valves (n = 3) and subsequently applied to human AS (n = 2). Relative lipid levels were spatially mapped and associated with different microdomains. Proteomics for non-calcified and calcified microdomains were performed to ascertain differences in expression. Increased pro-osteogenic and inflammatory lysophosphatidylcholine (LPC) 16:0 and 18:0 were co-localized with calcified microdomains. Proteomics analysis identified differential patterns in calcified microdomains with high LPC and low cholesterol as compared to non-calcified microdomains with low LPC and high cholesterol. Calcified microdomains had higher levels of: apolipoproteins (Apo) B-100 (p < 0.001) and Apo A-IV (p < 0.001), complement C3 and C4-B (p < 0.001), C5 (p = 0.007), C8 beta chain (p = 0.013) and C9 (p = 0.010), antithrombotic proteins alpha-2-macroglobulin (p < 0.0001) and antithrombin III (p = 0.002), and higher anti-calcific fetuin-A (p = 0.02), while the osteoblast differentiating factor transgelin (p < 0.0001), extracellular matrix proteins versican, prolargin, and lumican ( p < 0.001) and regulator protein complement factor H (p < 0.001) were higher in non-calcified microdomains. A combined lipidomic and proteomic approach provided insight into factors potentially contributing to progression from non-calcified to calcific disease in severe AS. Additional studies of these candidates and protein networks could yield new targets for slowing progression of AS.

Dataset Information

Assessment of pathological response to therapy using lipid mass spectrometry imaging.

Publications

Assessment of pathological response to therapy using lipid mass spectrometry imaging.

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