Elevated levels of 14-3-3 proteins, serotonin, gamma enolase and pyruvate kinase identified in clinical samples from patients diagnosed with colorectal cancer

Dowling, Paul; Hughes, David J.; Larkin, Annemarie; Meiller, Justine; Henry, Michael; Lynch, Vincent J.; Pardini, Barbara; Naccarati, Alessio; Levý, Miroslav; Vodička, Pavel; Neary, Paul; Clynes, Martin

doi:10.1016/j.cca.2014.12.005

Cited by 31 publications

(18 citation statements)

References 68 publications

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“…As metabolomics studies often identified a wide range of metabolites due to the variety of analytical platforms, clinical protocols, and sample handling procedures used, leveraging an independent population for replication using the same platform and similar protocols is essential to ensure robustness of findings. To date, only few studies have used a discovery‐replication design to reproduce results in independent study populations . Two of these studies investigated metabolic differences between colorectal cancer patients and apparently healthy individuals; a third study evaluated metabolomic differences between matched tumor and healthy colon tissue samples from colorectal cancer patients .…”

Section: Introductionmentioning

confidence: 99%

Plasma metabolites associated with colorectal cancer: A discovery‐replication strategy

Geijsen

Brezina

Keski‐Rahkonen

et al. 2019

Intl Journal of Cancer

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Colorectal cancer is known to arise from multiple tumorigenic pathways; however, the underlying mechanisms remain not completely understood. Metabolomics is becoming an increasingly popular tool in assessing biological processes. Previous metabolomics research focusing on colorectal cancer is limited by sample size and did not replicate findings in independent study populations to verify robustness of reported findings. Here, we performed a ultrahigh performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS) screening on EDTA plasma from 268 colorectal cancer patients and 353 controls using independent discovery and replication sets from two European cohorts (ColoCare Study: n = 180 patients/n = 153 controls; the Colorectal Cancer Study of Austria (CORSA) n = 88 patients/n = 200 controls), aiming to identify circulating plasma metabolites associated with colorectal cancer and to improve knowledge regarding colorectal cancer etiology. Multiple logistic regression models were used to test the association between disease state and metabolic features. Statistically significant associated features in the discovery set were taken forward and tested in the replication set to assure robustness of our findings. All models were adjusted for sex, age, BMI and smoking status and corrected for multiple testing using False Discovery Rate. Demographic and clinical data were abstracted from questionnaires and medical records.

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Section: Introductionmentioning

confidence: 99%

Plasma metabolites associated with colorectal cancer: A discovery‐replication strategy

Geijsen

Brezina

Keski‐Rahkonen

et al. 2019

Intl Journal of Cancer

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“…The optimized methodology has been previously described in detail (17). Peptide mixtures (5-µl volume) were loaded onto a C18 trap column [Acclaim™ PepMap™ 100 C18 LC column; 300 mm internal diameter (id) × 5 mm, 5 mm particle size, 100 Å pore size; Dionex Corporation; Thermo Fisher Scientific, Inc.).…”

Section: Methodsmentioning

confidence: 99%

“…Data alignment was based on the LC retention time of each sample (17). A reference sample was established, the retention times of all other replicates were aligned to this reference and peak intensities were then normalised.…”

Section: Methodsmentioning

confidence: 99%

Quantitative label-free mass spectrometry analysis of formalin-fixed, paraffin-embedded tissue representing the invasive cutaneous malignant melanoma proteome

et al. 2016

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Understanding the events at a protein level that govern the progression from melanoma in situ to invasive melanoma are important areas of current research to be developed. Recent advances in the analysis of formalin-fixed, paraffin-embedded tissue by proteomics, particularly using the filter-aided sample preparation protocol, has opened up the possibility of studying vast archives of clinical material and associated medical records. In the present study, quantitative protein profiling was performed using tandem mass spectrometry, and the proteome differences between melanoma in situ and invasive melanoma were compared. Biological pathway analyses revealed several signalling pathways differing between melanoma in situ and invasive melanoma, including metabolic pathways and the phosphoinositide 3-kinase-Akt signalling pathway. Selected proteins of interest (14–3-3ε and fatty acid synthase) were subsequently investigated using immunohistochemical analysis of tissue microarrays. Identifying the key proteins that play significant roles in the establishment of a more invasive phenotype in melanoma may ultimately aid diagnosis and treatment decisions.

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“…Such different behavior is much likely due to the ability of serotonin to act in a concentration-dependent manner, as well as in its capability to activate distinct signaling pathways, depending on the receptor subtype present at various tumor stages. Coherently, high serotonin levels, correlating with the tumor stage, distant metastases and a poor prognosis, have been found in the serum of patients with different solid tumors [131,[135][136][137], whereas low concentrations have been found in hepatocellular carcinoma patients, who showed recurrence after partial hepatectomy [118]; in untreated breast adenocarcinoma or malignant melanoma patients, where the phenotype (also associated with a high ATP/ADP ratio and index of delta storage pool deficiency) was more marked in regionally spread malignant tumors [138].…”

Section: Platelet-derived Bioactive Compoundsmentioning

confidence: 99%

The “Janus Face” of Platelets in Cancer

Catani

Savini

Tullio

et al. 2020

IJMS

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Besides their vital role in hemostasis and thrombosis, platelets are also recognized to be involved in cancer, where they play an unexpected central role: They actively influence cancer cell behavior, but, on the other hand, platelet physiology and phenotype are impacted by tumor cells. The existence of this platelet-cancer loop is supported by a large number of experimental and human studies reporting an association between alterations in platelet number and functions and cancer, often in a way dependent on patient, cancer type and treatment. Herein, we shall report on an update on platelet-cancer relationships, with a particular emphasis on how platelets might exert either a protective or a deleterious action in all steps of cancer progression. To this end, we will describe the impact of (i) platelet count, (ii) bioactive molecules secreted upon platelet activation, and (iii) microvesicle-derived miRNAs on cancer behavior. Potential explanations of conflicting results are also reported: Both intrinsic (heterogeneity in platelet-derived bioactive molecules with either inhibitory or stimulatory properties; features of cancer cell types, such as aggressiveness and/or tumour stage) and extrinsic (heterogeneous characteristics of cancer patients, study design and sample preparation) factors, together with other confounding elements, contribute to “the Janus face” of platelets in cancer. Given the difficulty to establish the univocal role of platelets in a tumor, a better understanding of their exact contribution is warranted, in order to identify an efficient therapeutic strategy for cancer management, as well as for better prevention, screening and risk assessment protocols.

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Elevated levels of 14-3-3 proteins, serotonin, gamma enolase and pyruvate kinase identified in clinical samples from patients diagnosed with colorectal cancer

Abstract: The diagnosis and management of CRC could be enhanced by the discovery and validation of new candidate biomarkers, as found in this study, aimed at facilitating early detection and/or patient stratification together with providing information on the complex behaviour of cancer cells.

Cited by 31 publications

References 68 publications

Plasma metabolites associated with colorectal cancer: A discovery‐replication strategy

Plasma metabolites associated with colorectal cancer: A discovery‐replication strategy

Quantitative label-free mass spectrometry analysis of formalin-fixed, paraffin-embedded tissue representing the invasive cutaneous malignant melanoma proteome

The “Janus Face” of Platelets in Cancer

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