Proteomics for Breast Cancer Urine Biomarkers

Beretov, Julia; Wasinger, Valerie C.; Graham, Peter; Millar, Ewan K.A.; Kearsley, John H.; Li, Yong

doi:10.1016/b978-0-12-800094-6.00004-2

Cited by 38 publications

(24 citation statements)

References 198 publications

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“…In an adult, approximately 150–180 L of plasma undergoes filtration through kidneys throughout a day and many proteins, peptides, and metabolites are excreted out of the body as urine. Hence, urine is supposed to have the information from whole body . Moreover, amount of urine is not a restrain for experiments because it is readily available and most importantly it can be collected noninvasively, and therefore making urine a choice of sample for biomarker discovery.…”

Section: Discussionmentioning

confidence: 99%

Urinary proteome alterations in HER2 enriched breast cancer revealed by multipronged quantitative proteomics

et al. 2016

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Globally, breast cancer is the second most common cancer among women. Although biomarker discoveries through various proteomic approaches of tissue and serum samples have been studied in breast cancer, urinary proteome alterations in breast cancer are least studied. Urine being a noninvasive biofluid and a significant source of proteins, it has the potential in early diagnosis of breast cancer. This study used complementary quantitative gel-based and gel-free proteomic approaches to find a panel of urinary protein markers that could discriminate HER2 enriched (HE) subtype breast cancer from the healthy controls. A total of 183 differentially expressed proteins were identified using three complementary approaches, namely 2D-DIGE, iTRAQ, and sequential window acquisition of all theoretical mass spectra. The differentially expressed proteins were subjected to various bioinformatics analyses for deciphering the biological context of these proteins using protein analysis through evolutionary relationships, database for annotation, visualization and integrated discovery, and STRING. Multivariate statistical analysis was undertaken to identify the set of most significant proteins, which could discriminate HE breast cancer from healthy controls. Immunoblotting and MRM-based validation in a separate cohort testified a panel of 21 proteins such as zinc-alpha2-glycoprotein, A2GL, retinol-binding protein 4, annexin A1, SAP3, SRC8, gelsolin, kininogen 1, CO9, clusterin, ceruloplasmin, and α1-antitrypsin could be a panel of candidate markers that could discriminate HE breast cancer from healthy controls.

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Section: Discussionmentioning

confidence: 99%

Urinary proteome alterations in HER2 enriched breast cancer revealed by multipronged quantitative proteomics

et al. 2016

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“…Advances in proteomics, especially in mass spectrometry (MS) [ 2 , 3 ] have rapidly changed our knowledge of urine proteins which have simultaneously led to the identification and quantification of thousands of unique proteins and peptides in a complex biological fluid [ 4 , 5 ]. Proteomic studies of urine are highly informative, and have been successfully used to discover novel markers for cancer diagnosis and surveillance [ 6 – 9 ] as well as for monitoring cancer progression [ 10 , 11 ]. Technological development combined with the addition of urine screening would increase the knowledge about patient status and further assist assessment and treatment in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Urine to Identify Breast Cancer Biomarker Candidates Using a Label-Free LC-MS/MS Approach

et al. 2015

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IntroductionBreast cancer is a complex heterogeneous disease and is a leading cause of death in women. Early diagnosis and monitoring progression of breast cancer are important for improving prognosis. The aim of this study was to identify protein biomarkers in urine for early screening detection and monitoring invasive breast cancer progression.MethodWe performed a comparative proteomic analysis using ion count relative quantification label free LC-MS/MS analysis of urine from breast cancer patients (n = 20) and healthy control women (n = 20).ResultsUnbiased label free LC-MS/MS-based proteomics was used to provide a profile of abundant proteins in the biological system of breast cancer patients. Data analysis revealed 59 urinary proteins that were significantly different in breast cancer patients compared to the normal control subjects (p<0.05, fold change >3). Thirty-six urinary proteins were exclusively found in specific breast cancer stages, with 24 increasing and 12 decreasing in their abundance. Amongst the 59 significant urinary proteins identified, a list of 13 novel up-regulated proteins were revealed that may be used to detect breast cancer. These include stage specific markers associated with pre-invasive breast cancer in the ductal carcinoma in-situ (DCIS) samples (Leucine LRC36, MAST4 and Uncharacterized protein CI131), early invasive breast cancer (DYH8, HBA, PEPA, uncharacterized protein C4orf14 (CD014), filaggrin and MMRN2) and metastatic breast cancer (AGRIN, NEGR1, FIBA and Keratin KIC10). Preliminary validation of 3 potential markers (ECM1, MAST4 and filaggrin) identified was performed in breast cancer cell lines by Western blotting. One potential marker MAST4 was further validated in human breast cancer tissues as well as individual human breast cancer urine samples with immunohistochemistry and Western blotting, respectively.ConclusionsOur results indicate that urine is a useful non-invasive source of biomarkers and the profile patterns (biomarkers) identified, have potential for clinical use in the detection of BC. Validation with a larger independent cohort of patients is required in the following study.

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“…Various studies have applied urinary proteomics to discover cancer biomarkers for the early diagnosis and monitoring of cancer [9][10][11]. However, most of these studies used clinical urine samples from breast cancer patients who had already had distant metastases to viscera or bone [10].…”

Section: Introductionmentioning

confidence: 99%

“…However, whether time-course analyses of urine proteins can reveal reliable cancer metastasis biomarkers at different stages of cancer metastasis is unclear, as urinary proteins are easily affected by complicated factors such as medicine and diet, especially in human samples.Therefore, using a small number of animal models can help to determine the direct relationship between urine protein changes and related diseases such as cancer metastasis because the genetic and environmental factors are minimized [8]. In addition, determining an exact description of cancer metastasis is very helpful for the identification of cancer metastasis biomarkers, especially in early stages.Various studies have applied urinary proteomics to discover cancer biomarkers for the early diagnosis and monitoring of cancer [9][10][11]. However, most of these studies used clinical urine samples from breast cancer patients who had already had distant metastases to viscera or bone [10].…”

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confidence: 99%

Early candidate biomarkers in urine of Walker-256 lung metastasis rat model

Wei

Zhang

et al. 2018

Preprint

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Cancer metastasis accounts for the majority of deaths by cancer. Detection of cancer metastasis at its early stage is important for the management and prediction of cancer progression. Urine, which is not regulated by homeostatic mechanisms, reflects systemic changes in the whole body and can potentially be used for the early detection of cancer metastasis. In this study, a lung metastasis of a Walker-256 rat model was established by tail-vein injection of Walker-256 cells. Urine samples were collected at days 2, 4, 6 and 9 after injection, and the urinary proteomes were profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The urinary protein patterns changed significantly with the development of Walker-256 lung metastasis. On the fourth day, lung metastasis nodules appeared. On the sixth day, clinical symptoms started. On days 2, 4, 6 and 9, 11, 25, 34 and 44 differential proteins were identified in 7 lung metastatic rats by LC-MS/MS. Seventeen of these 62 differential proteins were identified on the second day, and 18 of them were identified on the fourth day. The differential urinary proteins changed significantly two days before lung metastasis nodules appeared. Differential urinary proteins differed in Walker-256 lung metastasis rat models and Walker-256 subcutaneous rat models. A total of 9 differential proteins (NHRF1, CLIC1, EZRI, AMPN, ACY1A, HSP7C, BTD, NID2, and CFAD) were identified in 7 lung metastatic rats at one or more common time points, and these 9 differential proteins were not identified in the subcutaneous rat model. Seven of these 9 differential proteins were associated with both breast cancer and lung cancer, eight of the nine were identified on the second day, and 8 of the nine can be identified on the fourth day; these early changes in urine were also identified with differential abundances at late stages of lung metastasis.Our results indicate that (1) the urine proteome changed significantly, even on the second day after tail-vein injection of Walker-256 cells and that (2) the urinary differential proteins were different in Walker-256 lung metastatic tumors and Walker-256 subcutaneous tumors. Our results provide the potential to detect early breast cancer lung metastasis, monitor its progression and differentiate it from the same cancer cells grown at other locations. IntroductionCancer metastasis is a process in which cancer cells are disseminated from primary tumor tissue to different sites through blood vessels and lymphatic vessels. Lung, brain, bone and liver are the common metastatic organs in cancer patients [1]. Distant organ metastasis accounts for most cancer morbidity and mortality and nearly 90% of cancer death[2] and is usually accompanied by a poor 5-year survival rate as well as limited treatment strategies [3]. Due to special lung-specific immunoregulatory mechanisms, tumor colonization occurs more readily in an immunologically permissive environment [4]. Therefore, many cancer metastases such those of as breast cancer and malignant mela...

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Proteomics for Breast Cancer Urine Biomarkers

Cited by 38 publications

References 198 publications

Urinary proteome alterations in HER2 enriched breast cancer revealed by multipronged quantitative proteomics

Urinary proteome alterations in HER2 enriched breast cancer revealed by multipronged quantitative proteomics

Proteomic Analysis of Urine to Identify Breast Cancer Biomarker Candidates Using a Label-Free LC-MS/MS Approach

Early candidate biomarkers in urine of Walker-256 lung metastasis rat model

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