The focus of this article is to review the recent advances in proteome analysis of human body fluids, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, and amniotic fluid, as well as its applications to human disease biomarker discovery. We aim to summarize the proteomics technologies currently used for global identification and quantification of body fluid proteins, and elaborate the putative biomarkers discovered for a variety of human diseases through human body fluid proteome (HBFP) analysis. Some critical concerns and perspectives in this emerging field are also discussed. With the advances made in proteomics technologies, the impact of HBFP analysis in the search for clinically relevant disease biomarkers would be realized in the future.

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Human body fluid proteome analysis

Discovery of Urinary Biomarkers

https://www.europeanurology.com/article/S0302-2838(11)00677-4/pdf/prognostic-factors-and-predictive-models-in-renal-cell-carcinoma-a-contemporary-review

Prognostic Factors and Predictive Models in Renal Cell Carcinoma: A Contemporary Review

Small supernumerary marker chromosomes (sSMC), defined as additional centric chromosome fragments too small to be identified or characterized unambiguously by banding cytogenetics alone, are present in 0.043% of newborn children. Several attempts have been made to correlate certain sSMC with a specific clinical picture, resulting in the description of several syndromes such as the i(18p)-, der(22)-, i(12p)- (Pallister Killian syndrome) and inv dup(22)- (cat-eye) syndromes. However, most of the remaining sSMC including minute-, ring-, inverted-duplication- as well as complex-rearranged chromosomes, have not yet been correlated with clinical syndromes, mostly due to problems in their comprehensive characterization. Here we present an overview of sSMC, including the first attempt to address problems of nomenclature and their modes of formation, problems connected with mosaicism plus familial occurrence. The review also discusses the frequency of sSMC in prenatal, postnatal, and clinical cases, their chromosomal origin and their association with uniparental disomy. A short review of the up-to-date approaches available for sSMC characterization is included. Clinically relevant correlations concerning the presence of a specific sSMC and its phenotypic consequences should become available soon.

Small supernumerary marker chromosomes (sSMC) in humans.

Oncoproteomics is the study of proteins and their interactions in a cancer cell by proteomic technologies. Proteomic research first came to the fore with the introduction of two-dimensional gel electrophoresis. At the turn of the century, proteomics has been increasingly applied to cancer research with the wide-spread introduction of mass spectrometry and proteinchip. There is an intense interest in applying proteomics to foster an improved understanding of cancer pathogenesis, develop new tumor biomarkers for diagnosis, and early detection using proteomic portrait of samples. Oncoproteomics has the potential to revolutionize clinical practice, including cancer diagnosis and screening based on proteomic platforms as a complement to histopathology, individualized selection of therapeutic combinations that target the entire cancer-specific protein network, real-time assessment of therapeutic efficacy and toxicity, and rational modulation of therapy based on changes in the cancer protein network associated with prognosis and drug resistance. Besides, oncoproteomics is also applied to the discovery of new therapeutic targets and to the study of drug effects. In pace with the successful completion of the Human Genome Project, the wave of proteomics has raised the curtain on the postgenome era. The study of oncoproteomics provides mankind with a better understanding of neoplasia. In this article, the discovery of cancer biomarkers in recent years is reviewed. The challenges ahead and perspectives of oncoproteomics for biomarkers development are also addressed. With a wealth of information that can be applied to a broad spectrum of biomarker research projects, this review serves as a reference for biomarker researchers, scientists working in proteomics and bioinformatics, oncologists, pharmaceutical scientists, biochemists, biologists, and chemists.

/pdf/contribution-of-oncoproteomics-to-cancer-biomarker-discovery-4hq3q3gxl3.pdf

Contribution of oncoproteomics to cancer biomarker discovery

Small supernumerary marker chromosomes (sSMC) are still a major problem in clinical cytogenetics as they are too small to be characterized for their chromosomal origin by traditional banding techniques, but require molecular cyto- genetic techniques for their identification. Apart from the cor- relation of about one third of the sSMC cases with a specific clinical picture, i.e. the i(18p), der(22), i(12p) (Pallister Killian syndrome) and inv dup(22) (cat-eye) syndromes, most of the remaining sSMC have not yet been correlated with clinical syn- dromes. Recently, we reviewed the available 11600 sSMC

Small supernumerary marker chromosomes – progress towards a genotype-phenotype correlation

In order to achieve a comprehensive description of biological tissue, spectral information about proteins, lipids, nucleic acids, and other biochemical components need to be obtained concurrently. Different analytical techniques may be combined to record complementary information of the same sample. Established techniques, which can be utilized to elucidate the biochemistry of tissue samples are, for instance, MALDI-TOF-MS and Raman microscopic imaging. With this contribution, we combine these two techniques for the first time. The combination of both techniques allows the utilization and interpretation of complementary information (i.e., the information about the protein composition derived from the Raman spectra with data of the lipids analyzed by the MALDI-TOF measurements). Furthermore, we demonstrate how spectral information from MALDI-TOF experiments can be utilized to interpret Raman spectra.

Deeper understanding of biological tissue: quantitative correlation of MALDI-TOF and Raman imaging.

ProteinChip technology reveals distinctive protein expression profiles in the urine of bladder cancer patients.

Non-invasive prenatal diagnosis on fetal nucleated erythrocytes from the maternal circulation is hampered by the small number of nucleated erythrocytes and the uncertainty as to whether they are of fetal or maternal origin. To overcome the latter limitation, single nucleated erythrocytes were separated and enriched from maternal blood by a triple density gradient and a monoclonal antibody (CD71) in combination with a magnetic activated cell sorter. Single nucleated cells were microscopically examined, individually collected with extended Pasteur pipettes, and each transferred into separate caps for the polymerase chain reaction (PCR). The DNA of the single nucleated erythrocytes was amplified at least 50-fold with a random PCR technique, viz., primer extension preamplification. Precise differentiation between maternal and fetal nucleated erythrocytes was achieved via PCR by using primers flanking highly polymorphic nucleotide repeats (D1S53, ACTBP2 and D21S11) and with a XY-specific primer pair (amelogenin). A total of 134 putative nucleated erythrocytes were analyzed from blood samples of 19 pregnant women. With the help of the polymorphic repeats, 25% were assigned as being of maternal origin, 26% of fetal origin, and 48% were uninformative. In cases with male fetuses, the amelogenin primers revealed 30% of cells to be fetal nucleated erythrocytes, the remaining 70% being of maternal origin. The results indicate that the combination of random PCR and PCR-mediated polymorphism analysis on the DNA of single nucleated erythrocytes is a useful technique for non-invasive prenatal diagnosis.

Determination of the origin of single nucleated cells in maternal circulation by means of random PCR and a set of length polymorphisms

Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI MSI) is a method that allows the investigation of the molecular content of surfaces, in particular, tissues, within its morphological context. The applications of MALDI MSI in the field of large-scale mass spectrometric studies, which are typically denoted by the suffix “omics”, are steadily increasing. This is because, on the one hand, technical advances regarding sample collection and preparation, matrix application, instrumentation, and data processing have enhanced the molecular specificity and sensitivity of MALDI MSI; on the other hand, the focus of the “omics” community has moved from establishing an inventory of certain compound classes to exploring their spatial distribution to gain novel insights. Thus, the aim of this mini-review is twofold, to display the state-of-the-art in terms of technical aspects in MALDI MSI and to highlight selected applications in the last two years, which either have significantly advanced a certain “omics” field or have introduced a new one through pioneering efforts.

F. von Eggeling

Papers

Small supernumerary marker chromosomes – progress towards a genotype-phenotype correlation

Deeper understanding of biological tissue: quantitative correlation of MALDI-TOF and Raman imaging.

ProteinChip technology reveals distinctive protein expression profiles in the urine of bladder cancer patients.

Determination of the origin of single nucleated cells in maternal circulation by means of random PCR and a set of length polymorphisms

MALDI mass spectrometric imaging meets "omics": recent advances in the fruitful marriage.