iTRAQ-based Comparative Serum Proteomic Analysis of Prostate Cancer Patients with or without Bone Metastasis

Yan, Bo; Chen, Binshen; Min, Shaoju; Gao, Yubo; Zhang, Yiming; Xu, Peng; Li, Chaoming; Chen, Jiasheng; Luo, Guangheng; Liu, Chunxiao

doi:10.7150/jca.33497

Cited by 16 publications

(12 citation statements)

References 51 publications

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“…In contrast, CD59 glycoprotein (CD59) was detected only in the 3D d10-d14 samples. Similarly to our results, CD59 has previously been detected in blood plasma (Yan et al, 2019) and urine EVs (Lu et al, 2009) from prostate cancer patients, which would suggest that CD59 is predominantly a late-stage cargo of prostate cancer EVs.…”

Section: The Invasive Transition Leads To Major Differences In Ev Prosupporting

confidence: 91%

In vivo-mimicking 3D cultures secrete distinct extracellular vesicles upon cancer cell invasion

Henriksson

Luoto

Coelho-Rato

et al. 2020

Preprint

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Extracellular vesicles (EVs) loaded with biomolecules are important in intercellular communication and mediate local and long-range signals in cancer metastasis. However, it is currently unknown how the development of the primary tumor and onset of invasion affect the secretion and characteristics of EVs. In this study, we developed an EV production method utilizing in vivo-mimicking extracellular matrix-based 3D cultures, which allows tracking of EVs over the course of invasive development of tumor organoids. Using this method, combined with proteomic profiling, we show that PC3 human prostate cancer organoids secrete EVs with previously undefined protein cargo, which substantially differs from EV cargo of 2D cultured cells. Intriguingly, an increase in EV amounts and extensive changes in EV protein composition were detected upon invasive transition of the organoids. These results reveal that EV secretion and cargo loading are highly dependent on the developmental status of the tumor organoid, emphasizing the necessity of in vivo-mimicking conditions for discovery of novel cancer-derived EV components, applicable as diagnostic markers for cancer.

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Section: The Invasive Transition Leads To Major Differences In Ev Prosupporting

confidence: 91%

In vivo-mimicking 3D cultures secrete distinct extracellular vesicles upon cancer cell invasion

Henriksson

Luoto

Coelho-Rato

et al. 2020

Preprint

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“…Shotgun-based comparative proteomics technologies have emerged as the preferred tool, promising the systematic detection of discriminatory protein targets and their characteristic PTMs that collectively constitute molecular fingerprints secreted into blood or other tissues, reflecting the presence of cancer and the disease phenotype [ 62 , 86 , 87 , 88 ] ( Figure 1 ). The differentially expressed proteins reflect their functions and the associated pathways that are involved, and can potentially be used for early diagnostic intervention.…”

Section: Global Comparative Proteomics Versus Targeted Quantitativmentioning

confidence: 99%

Challenges and Opportunities in Clinical Applications of Blood-Based Proteomics in Cancer

Bhawal

Oberg

Zhang

et al. 2020

Cancers

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Blood is a readily accessible biofluid containing a plethora of important proteins, nucleic acids, and metabolites that can be used as clinical diagnostic tools in diseases, including cancer. Like the on-going efforts for cancer biomarker discovery using the liquid biopsy detection of circulating cell-free and cell-based tumor nucleic acids, the circulatory proteome has been underexplored for clinical cancer biomarker applications. A comprehensive proteome analysis of human serum/plasma with high-quality data and compelling interpretation can potentially provide opportunities for understanding disease mechanisms, although several challenges will have to be met. Serum/plasma proteome biomarkers are present in very low abundance, and there is high complexity involved due to the heterogeneity of cancers, for which there is a compelling need to develop sensitive and specific proteomic technologies and analytical platforms. To date, liquid chromatography mass spectrometry (LC-MS)-based quantitative proteomics has been a dominant analytical workflow to discover new potential cancer biomarkers in serum/plasma. This review will summarize the opportunities of serum proteomics for clinical applications; the challenges in the discovery of novel biomarkers in serum/plasma; and current proteomic strategies in cancer research for the application of serum/plasma proteomics for clinical prognostic, predictive, and diagnostic applications, as well as for monitoring minimal residual disease after treatments. We will highlight some of the recent advances in MS-based proteomics technologies with appropriate sample collection, processing uniformity, study design, and data analysis, focusing on how these integrated workflows can identify novel potential cancer biomarkers for clinical applications.

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“…More recent labelling strategies, such as Tandem mass tag (TMT) and isobaric tag for relative and absolute quantitation (iTRAQ), have gained popularity as these techniques apply isobaric tags providing MS2-level relative quantitation while boosting the MS1 signal intensity to improve chances of peptide detection [79,80]. A potential problem with these approaches is the co-isolation of precursor peptides that results in ratio compression.…”

Section: Protein Quantitationmentioning

confidence: 99%

Recent advances in mass spectrometry based clinical proteomics: applications to cancer research

2020

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Cancer biomarkers have transformed current practices in the oncology clinic. Continued discovery and validation are crucial for improving early diagnosis, risk stratification, and monitoring patient response to treatment. Profiling of the tumour genome and transcriptome are now established tools for the discovery of novel biomarkers, but alterations in proteome expression are more likely to reflect changes in tumour pathophysiology. In the past, clinical diagnostics have strongly relied on antibody-based detection strategies, but these methods carry certain limitations. Mass spectrometry (MS) is a powerful method that enables increasingly comprehensive insights into changes of the proteome to advance personalized medicine. In this review, recent improvements in MS-based clinical proteomics are highlighted with a focus on oncology. We will provide a detailed overview of clinically relevant samples types, as well as, consideration for sample preparation methods, protein quantitation strategies, MS configurations, and data analysis pipelines currently available to researchers. Critical consideration of each step is necessary to address the pressing clinical questions that advance cancer patient diagnosis and prognosis. While the majority of studies focus on the discovery of clinically-relevant biomarkers, there is a growing demand for rigorous biomarker validation. These studies focus on high-throughput targeted MS assays and multi-centre studies with standardized protocols. Additionally, improvements in MS sensitivity are opening the door to new classes of tumour-specific proteoforms including posttranslational modifications and variants originating from genomic aberrations. Overlaying proteomic data to complement genomic and transcriptomic datasets forges the growing field of proteogenomics, which shows great potential to improve our understanding of cancer biology. Overall, these advancements not only solidify MS-based clinical proteomics' integral position in cancer research, but also accelerate the shift towards becoming a regular component of routine analysis and clinical practice.

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iTRAQ-based Comparative Serum Proteomic Analysis of Prostate Cancer Patients with or without Bone Metastasis

Cited by 16 publications

References 51 publications

In vivo-mimicking 3D cultures secrete distinct extracellular vesicles upon cancer cell invasion

In vivo-mimicking 3D cultures secrete distinct extracellular vesicles upon cancer cell invasion

Challenges and Opportunities in Clinical Applications of Blood-Based Proteomics in Cancer

Recent advances in mass spectrometry based clinical proteomics: applications to cancer research

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