Proteomic Cancer Biomarkers in Human Biofluids

A special issue of Proteomes (ISSN 2227-7382).

Deadline for manuscript submissions: closed (31 July 2015) | Viewed by 20854

Special Issue Editor


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Guest Editor
Department of Oncology, Wayne State University, School of Medicine, 110 E. Warren Avenue, PR03GL, Detroit, MI 48201, USA
Interests: cancer-specific proteomes; protein biomarkers; tissue-specific biofluids; multianalyte biomarker panels; presymptomatic cancer diagnostics

Special Issue Information

Dear Colleagues,

The National Cancer Institute at the National Institutes of Health defines a biomarker as a “biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease”. Biomarkers can provide molecular signals of the status of a disease as well as provide information for targeted therapeutic interventions. The host response to cancer-specific proteins also provides diagnostic indicators suitable for monitoring tumor burden and the effectiveness of clinical interventions. Biomarkers have been employed to stratify cancer patients to the most effective treatment. Biomarkers for the early detection of cancer must result in a reduction in disease-specific mortality from cancer otherwise the medical community cannot be expected to adopt their use. Researchers now recognize that panels of biomarker analytes rather than single markers will be needed to have sufficient sensitivity and specificity for the presymptomatic detection of cancer. Proteomics studies have shown that there is considerable overlap of protein biomarkers even among unrelated tumors such that additional approaches are needed for tissue specificity.
One solution to the dilemma of specificity is to perform biomarker studies in biofluids other than serum or plasma. Because of the ease of using serum or plasma, most cancer biomarker studies utilize these biofluids. However, using other biofluids physiologically associated with a particular tissue may provide more organ specific tumor biomarkers. With this in mind we have primarily focused this issue on the use of nontraditional biofluids for cancer proteomic screening modalities and secondarily on biomarker proteins other than those secreted from tumor cells because they tend to identify cases with large, late stage tumors. Ideally a biomarker screening panel should identify a specific cancer sufficiently early when treatments can result in an increase in progression-free survival rather than simply a lead-time bias.

Prof. Dr. Michael A. Tainsky
Guest Editor

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Keywords

  • organ specific tumor biomarkers
  • early detection of cancer
  • biomarker screening panel
  • cancer-specific proteins
  • presymptomatic detection of cancer
  • biomarkers for targeted therapeutic interventions

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Published Papers (3 papers)

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Research

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415 KiB  
Article
Use of Aleuria alantia Lectin Affinity Chromatography to Enrich Candidate Biomarkers from the Urine of Patients with Bladder Cancer
by Sarah R. Ambrose, Naheema S. Gordon, James C. Goldsmith, Wenbin Wei, Maurice P. Zeegers, Nicholas D. James, Margaret A. Knowles, Richard T. Bryan and Douglas G. Ward
Proteomes 2015, 3(3), 266-282; https://doi.org/10.3390/proteomes3030266 - 3 Sep 2015
Cited by 6 | Viewed by 5511
Abstract
Developing a urine test to detect bladder tumours with high sensitivity and specificity is a key goal in bladder cancer research. We hypothesised that bladder cancer-specific glycoproteins might fulfill this role. Lectin-ELISAs were used to study the binding of 25 lectins to 10 [...] Read more.
Developing a urine test to detect bladder tumours with high sensitivity and specificity is a key goal in bladder cancer research. We hypothesised that bladder cancer-specific glycoproteins might fulfill this role. Lectin-ELISAs were used to study the binding of 25 lectins to 10 bladder cell lines and serum and urine from bladder cancer patients and non-cancer controls. Selected lectins were then used to enrich glycoproteins from the urine of bladder cancer patients and control subjects for analysis by shotgun proteomics. None of the lectins showed a strong preference for bladder cancer cell lines over normal urothlelial cell lines or for urinary glycans from bladder cancer patients over those from non-cancer controls. However, several lectins showed a strong preference for bladder cell line glycans over serum glycans and are potentially useful for enriching glycoproteins originating from the urothelium in urine. Aleuria alantia lectin affinity chromatography and shotgun proteomics identified mucin-1 and golgi apparatus protein 1 as proteins warranting further investigation as urinary biomarkers for low-grade bladder cancer. Glycosylation changes in bladder cancer are not reliably detected by measuring lectin binding to unfractionated proteomes, but it is possible that more specific reagents and/or a focus on individual proteins may produce clinically useful biomarkers. Full article
(This article belongs to the Special Issue Proteomic Cancer Biomarkers in Human Biofluids)
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2776 KiB  
Article
IPA Analysis of Cervicovaginal Fluid from Precancerous Women Points to the Presence of Biomarkers for the Precancerous State of Cervical Carcinoma
by Xaveer Van Ostade, Martin Dom and Geert Van Raemdonck
Proteomes 2014, 2(3), 426-450; https://doi.org/10.3390/proteomes2030426 - 13 Aug 2014
Cited by 7 | Viewed by 6357
Abstract
Despite large gaps in our knowledge on the intracellular mechanism leading to cervical cancer, the pathways induced by oncogenic high-risk Human Papilloma Virus (HPV) and those finally causing cervical cancer are increasingly being unraveled. Assuming that precancerous tissue is recognized and lysed by [...] Read more.
Despite large gaps in our knowledge on the intracellular mechanism leading to cervical cancer, the pathways induced by oncogenic high-risk Human Papilloma Virus (HPV) and those finally causing cervical cancer are increasingly being unraveled. Assuming that precancerous tissue is recognized and lysed by the immune system—which is in many cases incomplete because of the counteraction by the HPV virus—we hypothesize that several intracellular factors, involved in induction and development of precancerous lesions and/or cervical cancer are being released into the cervicovaginal fluid (CVF). These factors can then be seen as markers for the precancerous state, and when they persist they are indicative for an increased risk for cervical carcinoma. In a previous study, we analyzed the proteomic profiles of six CVF samples from women with different stages of precancerous lesions and compared these with the CVF proteomes from healthy women. Here, we extend these observations by investigating these proteomes by Ingenuity Pathway Analysis (IPA). We show that proteins in CVF from precancerous women are clearly more involved in pathways that make up the ‘hallmarks of cancer’, as compared to CVF proteins from healthy persons. Moreover, after literature search, proteins classified by IPA in the ‘cancer’ category, were more correlated with cervical cancer when they originated from CVF from precancerous women. Many of these proteins formed a network with angiotensin II as central mediator. The search for ‘network biomarkers’, rather than single biomarkers, could drastically increase specificity, sensitivity and prognostic value of cervical cancer diagnosis, making use of an easy to handle fluid, the CVF. Full article
(This article belongs to the Special Issue Proteomic Cancer Biomarkers in Human Biofluids)
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Review

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1167 KiB  
Review
High-Throughput Analysis of Plasma Hybrid Markers for Early Detection of Cancers
by Jung-hyun Rho and Paul D. Lampe
Proteomes 2014, 2(1), 1-17; https://doi.org/10.3390/proteomes2010001 - 13 Jan 2014
Cited by 11 | Viewed by 8536
Abstract
Biomarkers for the early detection of cancer in the general population have to perform with high sensitivity and specificity in order to prevent the costs associated with over-diagnosis. There are only a few current tissue or blood markers that are recommended for generalized [...] Read more.
Biomarkers for the early detection of cancer in the general population have to perform with high sensitivity and specificity in order to prevent the costs associated with over-diagnosis. There are only a few current tissue or blood markers that are recommended for generalized cancer screening. Despite the recognition that combinations of multiple biomarkers will likely improve their utility, biomarker panels are usually limited to a single class of molecules. Tissues and body fluids including plasma and serum contain not only proteins, DNA and microRNAs that are differentially expressed in cancers but further cancer specific information might be gleaned by comparing different classes of biomolecules. For example, the level of a certain microRNA might be related to the level of a particular protein in a cancer specific manner. Proteins might have cancer-specific post-translational modifications (e.g., phosphorylation or glycosylation) or lead to the generation of autoantibodies. Most currently approved biomarkers are glycoproteins. Autoantibodies can be produced as a host’s early surveillance response to cancer-specific proteins in pre-symptomatic and pre-diagnostic stages of cancer. Thus, measurement of the level of a protein, the level of its glycosylation or phosphorylation and whether autoantibodies are produced to it can yield multi-dimensional information on each protein. We consider specific proteins that show consistent cancer-specific changes in two or three of these measurements to be “hybrid markers”. We hypothesize these markers will suffer less variation between different individuals since one component can act to “standardize” the other measurement. As a proof of principle, a 180 plasma sample set consisting of 120 cases (60 colon cancers and 60 adenomas) and 60 controls were analyzed using our high-density antibody array for changes in their protein, IgG-complex and sialyl-Lewis A (SLeA) modified proteins. At p < 0.05, expression changes in 1,070 proteins, 49 IgG-complexes (11 present in the protein list) and 488 Lewis X-modified proteins (57 on the protein list) were observed. The biomarkers significant on both lists are potential hybrid markers. Thus, plasma hybrid markers have the potential to create a new class of early detection markers of cancers. Full article
(This article belongs to the Special Issue Proteomic Cancer Biomarkers in Human Biofluids)
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