|
1
|
Kumar Barik A, Mathew C, Sanoop PM, John RV, Adigal SS, Bhat S, Pai KM, Bhandary SV, Devasia T, Upadhya R, Kartha VB, Chidangil S. Protein profile pattern analysis: A multifarious, in vitro diagnosis technique for universal screening. J Chromatogr B Analyt Technol Biomed Life Sci 2024; 1232:123944. [PMID: 38056315 DOI: 10.1016/j.jchromb.2023.123944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 11/23/2023] [Accepted: 11/28/2023] [Indexed: 12/08/2023]
Abstract
Universal health care is attracting increased attention nowadays, because of the large increase in population all over the world, and a similar increase in life expectancy, leading to an increase in the incidence of non-communicable (various cancers, coronary diseases, neurological and old-age-related diseases) and communicable diseases/pandemics like SARS-COVID 19. This has led to an immediate need for a healthcare technology that should be cost-effective and accessible to all. A technology being considered as a possible one at present is liquid biopsy, which looks for markers in readily available samples like body fluids which can be accessed non- or minimally- invasive manner. Two approaches are being tried now towards this objective. The first involves the identification of suitable, specific markers for each condition, using established methods like various Mass Spectroscopy techniques (Surface-Enhanced Laser Desorption/Ionization Mass Spectroscopy (SELDI-MS), Matrix-Assisted Laser Desorption/Ionization (MALDI-MS), etc., immunoassays (Enzyme-Linked Immunoassay (ELISA), Proximity Extension Assays, etc.) and separation methods like 2-Dimensional Polyacrylamide Gel Electrophoresis (2-D PAGE), Sodium Dodecyl-Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE), Capillary Electrophoresis (CE), etc. In the second approach, no attempt is made the identification of specific markers; rather an efficient separation method like High-Performance Liquid Chromatography/ Ultra-High-Performance Liquid Chromatography (HPLC/UPLC) is used to separate the protein markers, and a profile of the protein pattern is recorded, which is analysed by Artificial Intelligence (AI)/Machine Learning (MI) methods to derive characteristic patterns and use them for identifying the disease condition. The present report gives a summary of the current status of these two approaches and compares the two in the use of their suitability for universal healthcare.
Collapse
Affiliation(s)
- Ajaya Kumar Barik
- Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Clint Mathew
- Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Pavithran M Sanoop
- Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Reena V John
- Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Sphurti S Adigal
- Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Sujatha Bhat
- Division of Microbiology, Department of Basic Medical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Keerthilatha M Pai
- Department of Dental Surgery, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University, Gangtok, Sikkim 737102, India
| | - Sulatha V Bhandary
- Department of Ophthalmology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Tom Devasia
- Department of Cardiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Rekha Upadhya
- Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - V B Kartha
- Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Santhosh Chidangil
- Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
| |
Collapse
|
|
2
|
Shergalis A, Bankhead A, Luesakul U, Muangsin N, Neamati N. Current Challenges and Opportunities in Treating Glioblastoma. Pharmacol Rev 2018; 70:412-445. [PMID: 29669750 PMCID: PMC5907910 DOI: 10.1124/pr.117.014944] [Citation(s) in RCA: 557] [Impact Index Per Article: 79.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor, has a high mortality rate despite extensive efforts to develop new treatments. GBM exhibits both intra- and intertumor heterogeneity, lending to resistance and eventual tumor recurrence. Large-scale genomic and proteomic analysis of GBM tumors has uncovered potential drug targets. Effective and "druggable" targets must be validated to embark on a robust medicinal chemistry campaign culminating in the discovery of clinical candidates. Here, we review recent developments in GBM drug discovery and delivery. To identify GBM drug targets, we performed extensive bioinformatics analysis using data from The Cancer Genome Atlas project. We discovered 20 genes, BOC, CLEC4GP1, ELOVL6, EREG, ESR2, FDCSP, FURIN, FUT8-AS1, GZMB, IRX3, LITAF, NDEL1, NKX3-1, PODNL1, PTPRN, QSOX1, SEMA4F, TH, VEGFC, and C20orf166AS1 that are overexpressed in a subpopulation of GBM patients and correlate with poor survival outcomes. Importantly, nine of these genes exhibit higher expression in GBM versus low-grade glioma and may be involved in disease progression. In this review, we discuss these proteins in the context of GBM disease progression. We also conducted computational multi-parameter optimization to assess the blood-brain barrier (BBB) permeability of small molecules in clinical trials for GBM treatment. Drug delivery in the context of GBM is particularly challenging because the BBB hinders small molecule transport. Therefore, we discuss novel drug delivery methods, including nanoparticles and prodrugs. Given the aggressive nature of GBM and the complexity of targeting the central nervous system, effective treatment options are a major unmet medical need. Identification and validation of biomarkers and drug targets associated with GBM disease progression present an exciting opportunity to improve treatment of this devastating disease.
Collapse
Affiliation(s)
- Andrea Shergalis
- Department of Medicinal Chemistry, College of Pharmacy, North Campus Research Complex, Ann Arbor, Michigan (A.S., U.L., N.N.); Biostatistics Department and School of Public Health, University of Michigan, Ann Arbor, Michigan (A.B.); and Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand (U.L., N.M.)
| | - Armand Bankhead
- Department of Medicinal Chemistry, College of Pharmacy, North Campus Research Complex, Ann Arbor, Michigan (A.S., U.L., N.N.); Biostatistics Department and School of Public Health, University of Michigan, Ann Arbor, Michigan (A.B.); and Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand (U.L., N.M.)
| | - Urarika Luesakul
- Department of Medicinal Chemistry, College of Pharmacy, North Campus Research Complex, Ann Arbor, Michigan (A.S., U.L., N.N.); Biostatistics Department and School of Public Health, University of Michigan, Ann Arbor, Michigan (A.B.); and Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand (U.L., N.M.)
| | - Nongnuj Muangsin
- Department of Medicinal Chemistry, College of Pharmacy, North Campus Research Complex, Ann Arbor, Michigan (A.S., U.L., N.N.); Biostatistics Department and School of Public Health, University of Michigan, Ann Arbor, Michigan (A.B.); and Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand (U.L., N.M.)
| | - Nouri Neamati
- Department of Medicinal Chemistry, College of Pharmacy, North Campus Research Complex, Ann Arbor, Michigan (A.S., U.L., N.N.); Biostatistics Department and School of Public Health, University of Michigan, Ann Arbor, Michigan (A.B.); and Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand (U.L., N.M.)
| |
Collapse
|
|
3
|
Grizzle WE, Semmes OJ, Bigbee W, Zhu L, Malik G, Oelschlager DK, Manne B, Manne U. The Need for Review and Understanding of SELDI/MALDI Mass Spectroscopy Data Prior to Analysis. Cancer Inform 2017. [DOI: 10.1177/117693510500100106] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Multiple studies have reported that surface enhanced laser desorption/ionization time of flight mass spectroscopy (SELDI-TOF-MS) is useful in the early detection of disease based on the analysis of bodily fluids. Use of any multiplex mass spectroscopy based approach as in the analysis of bodily fluids to detect disease must be analyzed with great care due to the susceptibility of multiplex and mass spectroscopy methods to biases introduced via experimental design, patient samples, and/or methodology. Specific biases include those related to experimental design, patients, samples, protein chips, chip reader and spectral analysis. Contributions to biases based on patients include demographics (e.g., age, race, ethnicity, sex), homeostasis (e.g., fasting, medications, stress, time of sampling), and site of analysis (hospital, clinic, other). Biases in samples include conditions of sampling (type of sample container, time of processing, time to storage), conditions of storage, (time and temperature of storage), and prior sample manipulation (freeze thaw cycles). Also, there are many potential biases in methodology which can be avoided by careful experimental design including ensuring that cases and controls are analyzed randomly. All the above forms of biases affect any system based on analyzing multiple analytes and especially all mass spectroscopy based methods, not just SELDI-TOF-MS. Also, all current mass spectroscopy systems have relatively low sensitivity compared with immunoassays (e.g., ELISA). There are several problems which may be unique to the SELDI-TOF-MS system marketed by Ciphergen®. Of these, the most important is a relatively low resolution (±0.2%) of the bundled mass spectrometer which may cause problems with analysis of data. Foremost, this low resolution results in difficulties in determining what constitutes a “peak” if a peak matching approach is used in analysis. Also, once peaks are selected, the peaks may represent multiple proteins. In addition, because peaks may vary slightly in location due to instrumental drift, long term identification of the same peaks may prove to be a challenge. Finally, the Ciphergen® system has some “noise” of the baseline which results from the accumulation of charge in the detector system. Thus, we must be very aware of the factors that may affect the use of proteomics in the early detection of disease, in determining aggressive subsets of cancers, in risk assessment and in monitoring the effectiveness of novel therapies.
Collapse
Affiliation(s)
| | | | - William Bigbee
- University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
| | - Liu Zhu
- University of Alabama at Birmingham, Birmingham, AL
| | | | | | - Barkha Manne
- University of Alabama at Birmingham, Birmingham, AL
| | | |
Collapse
|
|
4
|
Serum lipid profile discriminates patients with early lung cancer from healthy controls. Lung Cancer 2017; 112:69-74. [DOI: 10.1016/j.lungcan.2017.07.036] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Revised: 07/11/2017] [Accepted: 07/31/2017] [Indexed: 01/09/2023]
|
|
5
|
Wetmore BA, Merrick BA. Invited Review: Toxicoproteomics: Proteomics Applied to Toxicology and Pathology. Toxicol Pathol 2016; 32:619-42. [PMID: 15580702 DOI: 10.1080/01926230490518244] [Citation(s) in RCA: 122] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Global measurement of proteins and their many attributes in tissues and biofluids defines the field of proteomics. Toxicoproteomics, as part of the larger field of toxicogenomics, seeks to identify critical proteins and pathways in biological systems that are affected by and respond to adverse chemical and environmental exposures using global protein expression technologies. Toxicoproteomics integrates 3 disciplinary areas: traditional toxicology and pathology, differential protein and gene expression analysis, and systems biology. Key topics to be reviewed are the evolution of proteomics, proteomic technology platforms and their capabilities with exemplary studies from biology and medicine, a review of over 50 recent studies applying proteomic analysis to toxicological research, and the recent development of databases designed to integrate -Omics technologies with toxicology and pathology. Proteomics is examined for its potential in discovery of new biomarkers and toxicity signatures, in mapping serum, plasma, and other biofluid proteomes, and in parallel proteomic and transcriptomic studies. The new field of toxicoproteomics is uniquely positioned toward an expanded understanding of protein expression during toxicity and environmental disease for the advancement of public health.
Collapse
Affiliation(s)
- Barbara A Wetmore
- National Center for Toxicogenomics, National Institute of Environmental Health Sciences, Research Triangle Park, North Caroline 27709, USA
| | | |
Collapse
|
|
6
|
Song D, Yue L, Zhang J, Ma S, Zhao W, Guo F, Fan Y, Yang H, Liu Q, Zhang D, Xia Z, Qin P, Jia J, Yue M, Yu J, Zheng S, Yang F, Wang J. Diagnostic and prognostic significance of serum apolipoprotein C-I in triple-negative breast cancer based on mass spectrometry. Cancer Biol Ther 2016; 17:635-47. [PMID: 27260686 DOI: 10.1080/15384047.2016.1156262] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Women with triple-negative breast cancer (TNBC) have poor prognosis because of the aggressive nature of the tumor, delayed diagnosis and non-specific symptoms in the early stages. Identification of novel specific TNBC serum biomarkers for screening and therapeutic purposes therefore remains an urgent clinical requirement.We obtained serum samples from a total of 380 recruited individuals split into mining and testing sets, with the aim of screening for reliable protein biomarkers from TNBC and non-TNBC (NTNBC) sera. Samples were assessed using mass spectrometry, followed by receiver operating characteristic (ROC), survival and hazard function curve as well as multivariate Cox regression analyses to ascertain the potential of the protein constituents as diagnostic and prognostic biomarkers for TNBC.We identified upregulated apolipoprotein C-I (apoC-I) with a validated positive effect on TNBC tumorigenesis, with confirmation in an independent test set and minimization of systematic bias by pre-analytical parameters. The apoC-I protein had superior diagnostic ability in distinguishing between TNBC and NTNBC cases. Moreover, the protein presented a more robust potential prognostic factor for TNBC than NTNBC. The apoC-I protein identified in this study presents an effective novel diagnostic and prognostic biomarker for TNBC, indicating that measurement of the peak intensity at 7785 Da in serum samples could facilitate improved early detection and estimation of postoperative survival prognosis for TNBC.
Collapse
Affiliation(s)
- Dongjian Song
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China.,b Institute of Clinical Medicine, First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Lifang Yue
- c Department of Ultrasonography , Third Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Junjie Zhang
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Shanshan Ma
- d School of Life Science , Zhengzhou University , Zhengzhou , PR China
| | - Wei Zhao
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Fei Guo
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Yingzhong Fan
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Heying Yang
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Qiuliang Liu
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Da Zhang
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Ziqiang Xia
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Pan Qin
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Jia Jia
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Ming Yue
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| | - Jiekai Yu
- e Institute of Cancer, Second Affiliated Hospital, Zhejiang University , Hangzhou , PR China
| | - Shu Zheng
- e Institute of Cancer, Second Affiliated Hospital, Zhejiang University , Hangzhou , PR China
| | - Fuquan Yang
- f Proteomic Platform , Institute of Biophysics, Chinese Academy of Sciences , Beijing , PR China
| | - Jiaxiang Wang
- a Department of Pediatric Surgery , First Affiliated Hospital, Zhengzhou University , Zhengzhou , PR China
| |
Collapse
|
|
7
|
Diagnostic and prognostic role of serum protein peak at 6449 m/z in gastric adenocarcinoma based on mass spectrometry. Br J Cancer 2016; 114:929-38. [PMID: 27002935 PMCID: PMC4984799 DOI: 10.1038/bjc.2016.52] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Revised: 02/03/2016] [Accepted: 02/09/2016] [Indexed: 02/07/2023] Open
Abstract
Background: Gastric cancer (GC) is a highly aggressive cancer type associated with significant mortality owing to delayed diagnosis and non-specific symptoms observed in the early stages. Therefore, identification of novel specific GC serum biomarkers for screening purposes is an urgent clinical requirement. Methods: This study recruited a total of 432 serum samples from 296 GC patients split into the mining and testing sets. We aimed to screen for reliable protein biomarkers from matched serum samples based on mass spectrometry, followed by comparison with three representative conventional markers using receiver operating characteristic and survival curve analyses to ascertain their potential values as diagnostic and prognostic biomarkers for GC. Results: We identified an apoC-III fragment with confirmation in an independent test set from a second hospital. We found that the diagnostic ability of this fragment performed better than current standard GC diagnostic biomarkers both individually and in combination in distinguishing patients with GC from healthy individuals. Moreover, we found that this apoC-III protein fragment represents a more robust potential prognostic factor for GC than the three conventional markers. Conclusions: In view of these findings, we suggest that apoC-III protein fragment is a novel diagnostic and prognostic biomarker, a complement to conventional biomarkers in detecting GC.
Collapse
|
|
8
|
Abstract
Multifactorial diseases such as respiratory disease call for a global analysis of such disorders. Recent advances in protein profiling techniques may allow for early diagnosis of respiratory disease, which is crucial for intervention and treatment. In order to reduce false-positive rates, clinical diagnosis requires a high degree of sensitivity and specificity to be an effective screening tool. Protein profiles identified by ProteinChip (Ciphergen Biosystems) technology coupled with mass spectrometry affords a global analysis of clinical samples and is beginning to reach acceptable levels of sensitivity and specificity. Combining the profile with another diagnostic tool enhances the effectiveness of protein profiles to classify disease. Although current efforts have centered on serum protein profiling, the local environment of the lung may be better reflected in proteins of bronchoalveolar lavage or sputum. Identification of biomarkers of disease by protein profiling analyses may lead to an understanding of the mechanisms of this disease and contribute to the discovery of new therapeutics for the prevention and treatment of disease. Advancing these analyses are techniques such as ProteinChip mass spectrometry, laser capture microdissection, tissue microarrays and fluorescently labeled antibody bead arrays, which enable the direct global analysis of complex mixtures. Effective high-throughput and ease of use of clinical testing will arrive with improvements in bioinformatics and decreases in instrumentation costs.
Collapse
Affiliation(s)
- Susan E Boggs
- Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108, USA.
| |
Collapse
|
|
9
|
Indovina P, Marcelli E, Pentimalli F, Tanganelli P, Tarro G, Giordano A. Mass spectrometry-based proteomics: the road to lung cancer biomarker discovery. MASS SPECTROMETRY REVIEWS 2013; 32:129-142. [PMID: 22829143 DOI: 10.1002/mas.21355] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/13/2011] [Revised: 04/18/2012] [Accepted: 04/18/2012] [Indexed: 06/01/2023]
Abstract
Lung cancer is the leading cause of cancer death in men and women in Western nations, and is among the deadliest cancers with a 5-year survival rate of 15%. The high mortality caused by lung cancer is attributable to a late-stage diagnosis and the lack of effective treatments. So, it is crucial to identify new biomarkers that could function not only to detect lung cancer at an early stage but also to shed light on the molecular mechanisms that underlie cancer development and serve as the basis for the development of novel therapeutic strategies. Considering that DNA-based biomarkers for lung cancer showed inadequate sensitivity, specificity, and reproducibility, proteomics could represent a better tool for the identification of useful biomarkers and therapeutic targets for this cancer type. Among the proteomics technologies, the most powerful tool is mass spectrometry. In this review, we describe studies that use mass spectrometry-based proteomics technologies to analyze tumor proteins and peptides, which might represent new diagnostic, prognostic, and predictive markers for lung cancer. We focus in particular on those findings that hold promise to impact significantly on the clinical management of this disease.
Collapse
MESH Headings
- Animals
- Antineoplastic Agents/therapeutic use
- Biomarkers/blood
- Biomarkers/metabolism
- Biomarkers, Tumor/blood
- Biomarkers, Tumor/chemistry
- Biomarkers, Tumor/metabolism
- Chromatography, High Pressure Liquid
- Glycosylation/drug effects
- Humans
- Lung Neoplasms/blood
- Lung Neoplasms/diagnosis
- Lung Neoplasms/drug therapy
- Lung Neoplasms/metabolism
- Pleural Effusion, Malignant/blood
- Pleural Effusion, Malignant/drug therapy
- Pleural Effusion, Malignant/metabolism
- Prognosis
- Protein Processing, Post-Translational/drug effects
- Proteomics/methods
- Saliva/chemistry
- Saliva/drug effects
- Spectrometry, Mass, Electrospray Ionization
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Tandem Mass Spectrometry
Collapse
Affiliation(s)
- Paola Indovina
- Department of Human Pathology and Oncology, University of Siena, Siena, Italy
| | | | | | | | | | | |
Collapse
|
|
10
|
Choi JW, Liu H, Song H, Park JHY, Yun JW. Plasma marker proteins associated with the progression of lung cancer in obese mice fed a high-fat diet. Proteomics 2012; 12:1999-2013. [DOI: 10.1002/pmic.201100582] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Jung-Won Choi
- Department of Biotechnology,; Daegu University,; Kyungsan; Kyungbuk; Republic of Korea
| | - Hao Liu
- Department of Biotechnology,; Daegu University,; Kyungsan; Kyungbuk; Republic of Korea
| | - Hyerim Song
- Department of Food Science and Nutrition; Hallym University; Chuncheon; Republic of Korea
| | - Jung Han Yoon Park
- Department of Food Science and Nutrition; Hallym University; Chuncheon; Republic of Korea
| | - Jong Won Yun
- Department of Biotechnology,; Daegu University,; Kyungsan; Kyungbuk; Republic of Korea
| |
Collapse
|
|
11
|
Rathinam S, Ward DG, James ND, Rajesh PB. Proteomic analysis of resectable non-small cell lung cancer: post-resection serum samples may be useful in identifying potential markers. Interact Cardiovasc Thorac Surg 2011; 13:3-6. [PMID: 21525028 DOI: 10.1510/icvts.2010.260166] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) can be used to analyse peptides and proteins in clinical samples. A prospective study was undertaken on patients undergoing curative resection for non-small cell lung cancer (NSCLC): we used SELDI-TOF-MS to compare the proteomic profiles of serum from these patients both before surgical resection and after resection (disease-free) to identify potential biomarkers. Student t-tests were used, and a P-value of <0.01 was considered significant. Twenty-five patients with NSCLC [76% male, mean age 69 (range 53-81) years] were analysed. There were 13 squamous cell carcinomas, 10 adenocarcinomas and 2 large cell carcinomas with a stage distribution of four stage IA, 11 stage IB, five stage IIB, three stage IIIA, one stage IIIB and one stage IV. SELDI spectra generated with immobilised metal affinity chromatography arrays produced 170 peaks. Of these, 35 showed significant differences in their intensities between the preoperative and post-resection states (P<0.01). Postoperative samples in the disease-free state may represent good controls to identify biomarkers in NSCLC, avoiding the difficulties associated with cross-sectional studies. These pilot data need to be validated with larger numbers of patients.
Collapse
Affiliation(s)
- Sridhar Rathinam
- Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UK
| | | | | | | |
Collapse
|
|
12
|
Hsu PS, Wang YS, Huang SC, Lin YH, Chang CC, Tsang YW, Jiang JS, Kao SJ, Uen WC, Chi KH. Improving Detection Accuracy of Lung Cancer Serum Proteomic Profiling via Two-Stage Training Process. Proteome Sci 2011; 9:20. [PMID: 21496334 PMCID: PMC3102603 DOI: 10.1186/1477-5956-9-20] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2010] [Accepted: 04/17/2011] [Indexed: 01/17/2023] Open
Abstract
Background Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) is a frequently used technique for cancer biomarker research. The specificity of biomarkers detected by SELDI can be influenced by concomitant inflammation. This study aimed to increase detection accuracy using a two-stage analysis process. Methods Sera from 118 lung cancer patients, 72 healthy individuals, and 31 patients with inflammatory disease were randomly divided into training and testing groups by 3:2 ratio. In the training group, the traditional method of using SELDI profile analysis to directly distinguish lung cancer patients from sera was used. The two-stage analysis of distinguishing the healthy people and non-healthy patients (1st-stage) and then differentiating cancer patients from inflammatory disease patients (2nd-stage) to minimize the influence of inflammation was validated in the test group. Results In the test group, the one-stage method had 87.2% sensitivity, 37.5% specificity, and 64.4% accuracy. The two-stage method had lower sensitivity (> 70.1%) but statistically higher specificity (80%) and accuracy (74.7%). The predominantly expressed protein peak at 11480 Da was the primary splitter regardless of one- or two-stage analysis. This peak was suspected to be SAA (Serum Amyloid A) due to the similar m/z countered around this area. This hypothesis was further tested using an SAA ELISA assay. Conclusions Inflammatory disease can severely interfere with the detection accuracy of SELDI profiles for lung cancer. Using a two-stage training process will improve the specificity and accuracy of detecting lung cancer.
Collapse
Affiliation(s)
- Pei-Sung Hsu
- Division of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
13
|
Liu L, Liu J, Wang Y, Dai S, Wang X, Wu S, Wang J, Huang L, Xiao X, He D. A combined biomarker pattern improves the discrimination of lung cancer. Biomarkers 2010; 16:20-30. [DOI: 10.3109/1354750x.2010.521257] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
|
|
14
|
Lung cancer proteomics, clinical and technological considerations. J Proteomics 2010; 73:1851-63. [PMID: 20685322 DOI: 10.1016/j.jprot.2010.05.015] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2010] [Revised: 05/21/2010] [Accepted: 05/25/2010] [Indexed: 11/23/2022]
Abstract
The overall survival of lung cancer patients is disappointingly low. This is due to several factors, including the lack of an effective screening strategy to detect tumors at a potentially curable early stage, a marked resistance of lung cancer cells to drug treatment and a still superficial knowledge about the multifactorial cellular networks that are activated or suppressed during cancer progression. Furthermore, the armamentarium of clinicians and researchers in the field does not yet include reliable biomarkers to predict tumor response to treatment and foresee the natural history of the disease. In the present situation, a potential breakthrough is presented by proteomics technologies with the potential to discover relevant biomarkers which can be accurately quantified in multiplexed assays. Proteomics field can also contribute greatly in the understanding of mechanisms in tumor progression and treatment response. In this review we will describe the work that is being done in the field of lung cancer proteomics, focusing on clinically relevant questions that need to be addressed and on the possible applications of novel technologies.
Collapse
|
|
15
|
Shevchenko VE, Arnotskaya NE, Zaridze DG. Detection of lung cancer using plasma protein profiling by matrix-assisted laser desorption/ionization mass spectrometry. EUROPEAN JOURNAL OF MASS SPECTROMETRY (CHICHESTER, ENGLAND) 2010; 16:539-549. [PMID: 20625202 DOI: 10.1255/ejms.1080] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
There are no satisfactory plasma biomarkers which are available for the early detection and monitoring of lung cancer, one of the most frequent cancers worldwide. The aim of this study is to explore the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) to plasma proteomic patterns to distinguish lung cancer patients from healthy individuals. The EDTA plasma samples have been pre-fractionated using magnetic bead kits functionalized with weak cation exchange coatings. We compiled MS protein profiles for 90 patients with squamous cell carcinomas (SCC) and compared them with profiles from 187 healthy controls. The MALDI-ToF spectra were analyzed statistically using ClinProTools bioinformatics software. Depending on the sample used, up to 441 peaks/spectrum could be detected in a mass range of 1000-20,000 Da; 33 of these proteins had statistically differential expression levels between SCC and control plasma (P < 0.001). The series of the peaks were automatically chosen as potential biomarker patterns in the training set. They allowed the discrimination of plasma samples from healthy control and samples from SCC patients (sensitivity and specificity >90%) in external validation test. These results suggest that plasma MALDI-ToF MS protein profiling can distinguish patients with SCC and also from healthy individuals with relatively high sensitivity and specificity and that MALDI- ToF MS is a potential tool for the screening of lung cancer.
Collapse
Affiliation(s)
- Valeriy E Shevchenko
- N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow 115478, Russia.
| | | | | |
Collapse
|
|
16
|
Yang X, Wei KJ, Zhang L, Pan HY, Li J, Chen WT, Zhong LP, Zhang ZY. Increased expression of Cathepsin B in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 2009; 39:174-81. [PMID: 20042316 DOI: 10.1016/j.ijom.2009.11.018] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2008] [Revised: 09/24/2009] [Accepted: 11/27/2009] [Indexed: 11/26/2022]
Abstract
Previously, an in vitro cellular carcinogenesis model of oral squamous cell carcinoma (OSCC) was established with a line of human immortalized oral epithelial cells (HIOECs), a line of cancerous HB96 cells and another type of cell (HB56 cells) at the early stage of carcinogenesis. In this study, comparative proteomic analysis identified a panel of differentially expressed proteins among these cells. Cathepsin B was one of the significantly up-regulated proteins accompanying cellular transformation. Cathepsin B was further validated for its expression in the three cell lines and in clinical samples of tumour tissues and their adjacent normal epithelia from 30 primary OSCC patients. Western blot analysis and real-time PCR detected increased Cathepsin B protein and mRNA levels in the cancerous HB56 and HB96 cells over HIOECs. Immunohistochemistry and real-time PCR showed elevated Cathepsin B protein and mRNA levels in the tumour tissues over the adjacent non-malignant epithelia from OSCC patients. The results presented here suggest that the expression of Cathepsin B increases along with the cancerisation in OSCC both in vitro and in vivo, and it may serve as a candidate biomarker of OSCC.
Collapse
Affiliation(s)
- X Yang
- Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai 200011, China
| | | | | | | | | | | | | | | |
Collapse
|
|
17
|
Gast MCW, van Gils CH, Wessels LFA, Harris N, Bonfrer JMG, Rutgers EJT, Schellens JHM, Beijnen JH. Influence of sample storage duration on serum protein profiles assessed by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS). Clin Chem Lab Med 2009; 47:694-705. [PMID: 19416081 DOI: 10.1515/cclm.2009.151] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Issues have been raised concerning the robustness and validity of alleged serum markers discovered by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS). Pre-analytical variables have been shown to exert a profound effect on protein profiles, irrespective of true biological variation. However, little is known about the possible effects of sample storage duration on protein profiles. We, therefore, aimed to investigate the effects of extended storage duration on the serum protein profile. METHODS Archival sera from 140 breast cancer patients, stored at -30 degrees C for 1-11 years, were profiled by SELDI-TOF MS using immobilised metal affinity capture (IMAC) arrays, a condition applied in the majority of breast cancer biomarker discovery studies. RESULTS Fourteen peak clusters, structurally identified as C3a des-arginine anaphylatoxin and multiple fragments of albumin and fibrinogen, were found to be significantly associated with sample storage duration by five distinct patterns. These proteins have been described previously as potential cancer markers, rendering them specific to both disease and sample handling issues. CONCLUSIONS To prevent experimental variation being interpreted erroneously as disease associated variation, assessment of potential confounding pre-analytical parameters is a pre-requisite in biomarker discovery and validation studies. In addition, with respect to the different (non-)linear patterns observed in the current study, simply performing linear corrections to account for sample storage duration will not necessarily suffice.
Collapse
Affiliation(s)
- Marie-Christine W Gast
- Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands.
| | | | | | | | | | | | | | | |
Collapse
|
|
18
|
Findeisen P, Neumaier M. Mass spectrometry based proteomics profiling as diagnostic tool in oncology: current status and future perspective. Clin Chem Lab Med 2009; 47:666-84. [PMID: 19445650 DOI: 10.1515/cclm.2009.159] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Proteomics analysis has been heralded as a novel tool for identifying new and specific biomarkers that may improve diagnosis and monitoring of various disease states. Recent years have brought a number of proteomics profiling technologies. Although proteomics profiling has resulted in the detection of disease-associated differences and modification of proteins, current proteomics technologies display certain limitations that are hampering the introduction of these new technologies into clinical laboratory diagnostics and routine applications. In this review, we summarize current advances in mass spectrometry based biomarker discovery. The promises and challenges of this new technology are discussed with particular emphasis on diagnostic perspectives of mass-spectrometry based proteomics profiling for malignant diseases.
Collapse
Affiliation(s)
- Peter Findeisen
- Institute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, Heidelberg, Germany.
| | | |
Collapse
|
|
19
|
Qiu FM, Yu JK, Chen YD, Jin QF, Sui MH, Huang J. Mining novel biomarkers for prognosis of gastric cancer with serum proteomics. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2009; 28:126. [PMID: 19740432 PMCID: PMC2753349 DOI: 10.1186/1756-9966-28-126] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/06/2009] [Accepted: 09/09/2009] [Indexed: 12/15/2022]
Abstract
Background Although gastric caner (GC) remains the second cause of cancer-related death, useful biomarkers for prognosis are still unavailable. We present here the attempt of mining novel biomarkers for GC prognosis by using serum proteomics. Methods Sera from 43 GC patients and 41 controls with gastritis as Group 1 and 11 GC patients as Group 2 was successively detected by Surface Enhanced Laser Desorption/ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS) with Q10 chip. Peaks were acquired by Ciphergen ProteinChip Software 3.2.0 and analyzed by Zhejiang University-ProteinChip Data Analysis System (ZJU-PDAS). CEA level were evaluated by chemiluminescence immunoassay. Results After median follow-up periods of 33 months, Group 1 with 4 GC patients lost was divided into 20 good-prognosis GC patients (overall survival more than 24 months) and 19 poor-prognosis GC patients (no more than 24 months). The established prognosis pattern consisted of 5 novel prognosis biomarkers with 84.2% sensitivity and 85.0% specificity, which were significantly higher than those of carcinoembryonic antigen (CEA) and TNM stage. We also tested prognosis pattern blindly in Group 2 with 66.7% sensitivity and 80.0% specificity. Moreover, we found that 4474-Da peak elevated significantly in GC and was associated with advanced stage (III+IV) and short survival (p < 0.03). Conclusion We have identified a number of novel biomarkers for prognosis prediction of GC by using SELDI-TOF-MS combined with sophisticated bioinformatics. Particularly, elevated expression of 4474-Da peak showed very promising to be developed into a novel biomarker associated with biologically aggressive features of GC.
Collapse
Affiliation(s)
- Fu-Ming Qiu
- Department of Oncology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
| | | | | | | | | | | |
Collapse
|
|
20
|
Qiu F, Liu HY, Dong ZN, Feng YJ, Zhang XJ, Tian YP. Searching for Potential Ovarian Cancer Biomarkers with Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. ACTA ACUST UNITED AC 2009; 1:80-90. [PMID: 20664751 DOI: 10.5099/aj090100080] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Ovarian cancer is a common gynecological malignant disease, causing more deaths among women .The key objective in the treatment of ovarian cancer is early diagnosis. The objective of our study was to seek new ovarian cancer biomarkers based on a serum protein profile with the aim of discriminating ovarian cancer patients from healthy controls. An MB-WCX kit was used to analyze serum samples obtained from 20 ovarian cancer patients and 20 healthy controls and then we generated MALDI-TOF protein profiles from the analysis. After pre-processing of the spectra, linear analysis with ClinProTools bioinformatics software was used to classify protein profiles and search for prominent peaks that could be used as potential ovarian cancer biomarkers. Using ClinproTools bioinformatics and statistical software, we found 5 prominent expressed proteins in the ovarian cancer and healthy control groups. The mass to charge ratio were 4648.21(m/z), 9294.03(m/z), 3886.1(m/z), 9066.38(m/z) and 4254.71(m/z), respectively, and the former four proteins were expressed higher in the ovarian cancer patients, but the later one was expressed at lower levels in the cancer patients. The sensitivity and specificity were both more than 90%. From our study, we found that MALDI-TOF MS is a high-throughput sample preparation method and is a new potential tool for the diagnosis of human disease, not only to search for new early detection biomarkers in the ovarian cancer patients' serum samples, but also with a potential use for routine clinical work.
Collapse
Affiliation(s)
- Feng Qiu
- Department of Clinical Biochemistry, Chinese PLA General Hospital, 28 Fu-Xing Road, Beijing 100853, China
| | | | | | | | | | | |
Collapse
|
|
21
|
Liu D, Cao L, Yu J, Que R, Jiang W, Zhou Y, Zhu L. Diagnosis of pancreatic adenocarcinoma using protein chip technology. Pancreatology 2008; 9:127-35. [PMID: 19077463 DOI: 10.1159/000178883] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2007] [Accepted: 03/21/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND To develop a serum-specific protein fingerprint which is capable of differentiating samples from patients with pancreatic cancer and those with other pancreatic conditions. METHODS We used SELDI-TOF-MS coupled with CM10 chips and bioinformatics tools to analyze a total of 118 serum samples in this study; 78 serum samples were analyzed to establish the diagnostic models and the other 40 samples were analyzed on the second day as an independent test set. RESULTS The analysis of this independent test set yielded a specificity of 91.6% and a sensitivity of 91.6% for pattern 1, which distinguished pancreatic adenocarcinoma (PC) from healthy individuals and a specificity of 80.0% and a sensitivity of 90.9% for pattern 2, which distinguished PC from chronic pancreatitis. CONCLUSION This study indicated that the SELDI-TOF-MS technique can facilitate the discovery of better serum tumor biomarkers and a combination of specific models is more accurate than a single model in diagnosis of PC.
Collapse
Affiliation(s)
- Daren Liu
- Department of Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China
| | | | | | | | | | | | | |
Collapse
|
|
22
|
|
|
23
|
Mao L, Dong H, Yang P, Zhou H, Huang X, Lin X, Kijlstra A. MALDI-TOF/TOF-MS reveals elevated serum haptoglobin and amyloid A in Behcet's disease. J Proteome Res 2008; 7:4500-7. [PMID: 18754684 DOI: 10.1021/pr800279m] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Behcet's disease (BD) is a multisystemic autoimmune disease with unclear etiology and pathogenesis. To screen aberrant serum proteins in BD, serum samples were obtained from eight male BD patients with active uveitis and eight male healthy volunteers with informed consent. The serum samples from active BD patients and normal controls were pooled. Highly abundant serum proteins (albumin and IgG) were depleted from these two samples using an affinity capture based kit. The obtained samples were subjected to two-dimensional gel electrophoresis (2-DE). Protein spots were visualized with the "blue silver" staining. Differently expressed proteins were subsequently identified by matrix-assisted laser desorption /ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Western blot and enzyme-linked immunosorbent assay (ELISA) were performed using the serum samples from 18 patients with active BD, 6 patients with inactive BD, 22 patients with Vogt-Koyanagi-Harada (VKH) syndrome, and 20 healthy volunteers to validate the results of 2-DE and MS. Proteomic profiles of the pooled samples were compared, and approximately 800 protein spots were observed in each of the gels. Expression levels of four of the protein spots in active BD were significantly higher than those in the normal controls. Mass spectrometric protein identification revealed that the four protein spots corresponded to two proteins: haptoglobin (Hp) and serum amyloid A (SAA). Western blot and ELISA showed that Hp was only overexpressed in active BD but not in inactive BD, VKH syndrome, or healthy controls. An obvious band of SAA was detected in 72.2% of the serum samples from BD patients, whereas a vague band of this protein was found in 10.0% of the tested normal samples and 9.1% of VKH samples. Our results revealed a significantly increased expression of Hp and SAA in serum of active BD patients. These two proteins may be involved in the development of BD.
Collapse
Affiliation(s)
- Liming Mao
- Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology of Sun Yat-sen University, Guangzhou, P.R. China
| | | | | | | | | | | | | |
Collapse
|
|
24
|
Koehn J, Krapfenbauer K, Huber S, Stein E, Sutter W, Watzinger F, Erovic BM, Thurnher D, Schindler T, Fountoulakis M, Turhani D. Potential Involvement of MYC- and p53-Related Pathways in Tumorigenesis in Human Oral Squamous Cell Carcinoma Revealed by Proteomic Analysis. J Proteome Res 2008; 7:3818-29. [DOI: 10.1021/pr800077a] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Jadranka Koehn
- Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria, Novartis Institutes for Biomedical Research, Novartis, Vienna, Austria, Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria, and Roche Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland
| | - Kurt Krapfenbauer
- Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria, Novartis Institutes for Biomedical Research, Novartis, Vienna, Austria, Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria, and Roche Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland
| | - Susanna Huber
- Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria, Novartis Institutes for Biomedical Research, Novartis, Vienna, Austria, Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria, and Roche Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland
| | - Elisabeth Stein
- Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria, Novartis Institutes for Biomedical Research, Novartis, Vienna, Austria, Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria, and Roche Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland
| | - Walter Sutter
- Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria, Novartis Institutes for Biomedical Research, Novartis, Vienna, Austria, Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria, and Roche Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland
| | - Franz Watzinger
- Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria, Novartis Institutes for Biomedical Research, Novartis, Vienna, Austria, Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria, and Roche Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland
| | - Boban M. Erovic
- Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria, Novartis Institutes for Biomedical Research, Novartis, Vienna, Austria, Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria, and Roche Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland
| | - Dietmar Thurnher
- Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria, Novartis Institutes for Biomedical Research, Novartis, Vienna, Austria, Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria, and Roche Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland
| | - Thomas Schindler
- Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria, Novartis Institutes for Biomedical Research, Novartis, Vienna, Austria, Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria, and Roche Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland
| | - Michael Fountoulakis
- Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria, Novartis Institutes for Biomedical Research, Novartis, Vienna, Austria, Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria, and Roche Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland
| | - Dritan Turhani
- Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria, Novartis Institutes for Biomedical Research, Novartis, Vienna, Austria, Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria, and Roche Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland
| |
Collapse
|
|
25
|
Serum Proteomic Profiling of Lung Cancer in High-Risk Groups and Determination of Clinical Outcomes. J Thorac Oncol 2008; 3:840-50. [DOI: 10.1097/jto.0b013e31817e464a] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
|
|
26
|
Chan CML, Wong SCC, Lam MYY, Hui EP, Chan JKC, Lo ESF, Cheuk W, Wong MCK, Tsao SW, Chan ATC. Proteomic comparison of nasopharyngeal cancer cell lines C666-1 and NP69 identifies down-regulation of annexin II and beta2-tubulin for nasopharyngeal carcinoma. Arch Pathol Lab Med 2008; 132:675-83. [PMID: 18384219 DOI: 10.5858/2008-132-675-pconcc] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/12/2007] [Indexed: 11/06/2022]
Abstract
CONTEXT Nasopharyngeal carcinoma (NPC), common in southern China and North Africa, has a complex etiology involving interplay between viral, environmental, and hereditary factors and is almost constantly associated with the Epstein-Barr virus. Since the prognosis of locally advanced and metastatic diseases is poor, increased understanding of the pathogenesis of NPC would be important for discovering novel markers for patients' management. OBJECTIVES To compare the proteomic expression profile between an Epstein-Barr virus-associated NPC cell line (C666-1) and a normal NP cell line (NP69). The proteins with differential expression were analyzed in 40 undifferentiated NPC paraffin-embedded specimens. DESIGN Differentially expressed proteins discovered between the two cell lines were identified by mass spectrometry. After confirmation by immunocytochemical staining, their expression in patient samples was measured using 40 pairs of undifferentiated NPCs together with their adjacent normal epithelia. RESULTS Proteomic findings indicated that adenosine triphosphate synthase alpha chain was up-regulated, whereas annexin II, annexin V, beta(2)-tubulin, and profilin 1 were down-regulated. After confirming the results in agar-processed cell lines, annexin II and beta(2)-tubulin expression were found to be lower in tumor cells than in adjacent normal epithelial cells in 100% and 90% of the patients' specimens, respectively. Finally, annexin II down-regulation was positively associated with lymph node metastasis, suggesting that it may be a prognostic factor in NPC. CONCLUSIONS The results suggest that annexin II and beta(2)-tubulin down-regulation is important in NPC formation and may represent potential targets for further investigations.
Collapse
Affiliation(s)
- Charles M L Chan
- Department of Clinical Oncology, Sir Y. K. Pao Centre for Cancer, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
27
|
SELDI-TOF MS profiling of serum for detection of laryngeal squamous cell carcinoma and the progression to lymph node metastasis. J Cancer Res Clin Oncol 2008; 134:769-76. [DOI: 10.1007/s00432-007-0344-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2007] [Accepted: 12/07/2007] [Indexed: 11/26/2022]
|
|
28
|
Zinkin NT, Grall F, Bhaskar K, Otu HH, Spentzos D, Kalmowitz B, Wells M, Guerrero M, Asara JM, Libermann TA, Afdhal NH. Serum Proteomics and Biomarkers in Hepatocellular Carcinoma and Chronic Liver Disease. Clin Cancer Res 2008; 14:470-7. [DOI: 10.1158/1078-0432.ccr-07-0586] [Citation(s) in RCA: 154] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
|
|
29
|
Conrad DH, Goyette J, Thomas PS. Proteomics as a method for early detection of cancer: a review of proteomics, exhaled breath condensate, and lung cancer screening. J Gen Intern Med 2008; 23 Suppl 1:78-84. [PMID: 18095050 PMCID: PMC2150625 DOI: 10.1007/s11606-007-0411-1] [Citation(s) in RCA: 83] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The study of expressed proteins in neoplasia is undergoing a revolution with the advent of proteomic analysis. Unlike genomic studies where individual changes may have no functional significance, protein expression is closely aligned with cellular activity. This perspective will review proteomics as a method of detecting markers of neoplasia with a particular emphasis on lung cancer and the potential to sample the lung by exhaled breath condensate (EBC). EBC collection is a simple, new, and noninvasive technique, which allows sampling of lower respiratory tract fluid. EBC enables the study of a wide variety of biological markers from low molecular weight mediators to macromolecules, such as proteins, in a range of pulmonary diseases. EBC may be applied to the detection of lung cancer where it could be a tool in early diagnosis. This perspective will explore the potential of applying proteomics to the EBC from lung cancer patients as an example of detecting potential biomarkers of disease and progression.
Collapse
Affiliation(s)
- Dean H Conrad
- Inflammatory Diseases Research Unit, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | | | | |
Collapse
|
|
30
|
Collings FB, Vaidya VS. Novel technologies for the discovery and quantitation of biomarkers of toxicity. Toxicology 2007; 245:167-74. [PMID: 18237837 DOI: 10.1016/j.tox.2007.11.020] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2007] [Accepted: 11/28/2007] [Indexed: 12/31/2022]
Abstract
Reliable biomarkers of toxicity are necessary both for the safe conduct of pre-clinical and clinical trials, and are increasingly needed for accurate clinical evaluation of treatment regimens with the potential to cause tissue injury. Recent advances in technology have added several new tools to the biomarker screening toolkit and improved the throughput of existing quantitative assays. Genomics, proteomics, and metabolomics have provided a wealth of data in the search for predictive, specific biomarkers. Multiplexed ELISA-based assay systems, silicon nanowire arrays, and patterned paper present unique abilities for fast, efficient sample analysis over a broad dynamic range. Powerful integrative systems biology software and growing open-source data repositories offer new ways to share, reduce, and analyze data from multiple sources. Novel technologies reviewed here have the potential to significantly reduce assay time and cost and improve the sensitivity of screening methods for candidate biomarkers of toxicity.
Collapse
Affiliation(s)
- Fitz B Collings
- Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine, Rm 550, 4 Blackfan Circle, Boston, MA 02115, United States.
| | | |
Collapse
|
|
31
|
Liu L, Liu J, Dai S, Wang X, Wu S, Wang J, Huang L, Xiao X, He D. Reduced transthyretin expression in sera of lung cancer. Cancer Sci 2007; 98:1617-24. [PMID: 17683510 PMCID: PMC11159885 DOI: 10.1111/j.1349-7006.2007.00576.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Lung cancer is a leading cause of cancer death worldwide, and very few specific biomarkers can be used in its clinical diagnosis. Using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (MS) to find novel serum biomarkers for lung cancer, we analyzed 227 serum samples, including 146 lung cancers, 41 benign lung diseases and 40 normal individuals. Three peaks, at 13.78, 13.90 and 14.07 k m/z, were significantly lower in lung cancer sera compared with sera from normal individuals (P < 0.001), whereas these peaks were higher than those in the sera of benign lung diseases (P < 0.001). The peaks were identified as native transthyretin (TTR) and its two variants by one-dimensional polyacrylamide gel electrophoresis, ESI-MS/MS, immunoprecipitation and western blot analysis. An enzyme-linked immunosorbent assay indicated that TTR levels were consistent with surface-enhanced laser desorption-ionization analysis in all groups tested. It gave 78.5% sensitivity and 77.5% specificity for lung cancer versus normal at the cut-off point 115 microg/mL, and 66.7% sensitivity and 64.4% specificity for lung cancer versus benign lung diseases at the cut-off point 88.5 microg/mL. Therefore, TTR may be useful as a biomarker to improve the diagnosis of lung cancer.
Collapse
Affiliation(s)
- Liyun Liu
- Key laboratory for Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing 100875, China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Au JSK, Cho WCS, Yip TT, Yip C, Zhu H, Leung WWF, Tsui PYB, Kwok DLP, Kwan SSM, Cheng WW, Tzang LCH, Yang M, Law SCK. Deep proteome profiling of sera from never-smoked lung cancer patients. Biomed Pharmacother 2007; 61:570-577. [PMID: 17913442 DOI: 10.1016/j.biopha.2007.08.017] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Previous studies on the serum proteome are hampered by the huge dynamic range of concentration of different protein species. The use of Equalizer Beads coupled with a combinatorial library of ligands has been shown to allow access to many low-abundance proteins or polypeptides undetectable by classical analytical methods. This study focused on never-smoked lung cancer, which is considered to be more homogeneous and distinct from smoking-related cases both clinically and biologically. Serum samples obtained from 42 never-smoked lung cancer patients (28 patients with active untreated disease and 14 patients with tumor resected) were compared with those from 30 normal control subjects using the pioneering Equalizer Beads technology followed by subsequent analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Eighty-five biomarkers were significantly different between lung cancer and normal control. The application of classification algorithms based on significant biomarkers achieved good accuracy of 91.7%, 80% and 87.5% in class-prediction with respect to presence or absence of disease, subsequent development of metastasis and length of survival (longer or shorter than median) respectively. Support vector machine (SVM) performed best overall. We have proved the feasibility and convenience of using the Equalizer Beads technology to study the deep proteome of the sera of lung cancer patients in a rapid and high-throughput fashion, and which enables detection of low abundance polypeptides/proteins biomarkers. Coupling with classification algorithms, the technologies will be clinically useful for diagnosis and prediction of prognosis in lung cancer.
Collapse
Affiliation(s)
- Joseph S K Au
- Department of Clinical Oncology, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Abstract
Proteomic studies have generated numerous datasets of potential diagnostic, prognostic, and therapeutic significance in human cancer. Two key technologies underpinning these studies in cancer tissue are two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry (MS). Although surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF)-MS is the mainstay for serum or plasma analysis, other methods including isotope-coded affinity tag technology, reverse-phase protein arrays, and antibody microarrays are emerging as alternative proteomic technologies. Because there is little overlap between studies conducted with these approaches, confirmation of these advanced technologies remains an elusive goal. This problem is further exacerbated by lack of uniform patient inclusion and exclusion criteria, low patient numbers, poor supporting clinical data, absence of standardized sample preparation, and limited analytical reproducibility (in particular of 2D-PAGE). Despite these problems, there is little doubt that the proteomic approach has the potential to identify novel diagnostic biomarkers in cancer. In therapeutic proteomics, the challenge is significant due to the complexity systems under investigation (i.e., cells generate over 10(5) different polypeptides). However, the most significant contribution of therapeutic proteomics research is expected to derive not from single experiments, but from the synthesis and comparison of large datasets obtained under different conditions (e.g., normal, inflammation, cancer) and in different tissues and organs. Thus, standardized processes for storing and retrieving data obtained with different technologies by different research groups will have to be developed. Shifting the emphasis of cancer proteomics from technology development and data generation to careful study design, data organization, formatting, and mining is crucial to answer clinical questions in cancer research.
Collapse
Affiliation(s)
- M A Reymond
- Department of Surgery, University of Magdeburg, Germany
| | | |
Collapse
|
|
34
|
Affiliation(s)
- Haleem J Issaq
- Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, P.O. Box B, Frederick, Maryland 21702, USA
| | | | | |
Collapse
|
|
35
|
Dai S, Wang X, Liu L, Liu J, Wu S, Huang L, Xiao X, He D. Discovery and identification of Serum Amyloid A protein elevated in lung cancer serum. ACTA ACUST UNITED AC 2007; 50:305-11. [PMID: 17609886 DOI: 10.1007/s11427-007-0053-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2006] [Accepted: 01/28/2007] [Indexed: 01/10/2023]
Abstract
Two hundred and eighteen serum samples from 175 lung cancer patients and 43 healthy individuals were analyzed by using Surface Enhaced Laser Desorption/Ionization Time of Flight Mass Spectrome-try (SELDI-TOF-MS). The data analyzed by both Biomarker Wizardtrade mark and Biomarker Patternstrade mark software showed that a protein peak with the molecular weight of 11.6 kDa significantly increased in lung cancer. Meanwhile, the level of this biomarker was progressively increased with the clinical stages of lung cancer. The candidate biomarker was then obtained from tricine one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis by matching the molecular weight with peaks on WCX2 chips and was identified as Serum Amyloid A protein (SAA) by MALDI/MS-MS and database searching. It was further validated in the same serum samples by immunoprecipitation with commercial SAA antibody. To confirm the SAA differential expression in lung cancer patients, the same set of serum samples was measured by ELISA assay. The result showed that at the cutoff point 0.446 (OD value) on the Receiver Operating Characteristic (ROC) curve, SAA could better discriminate lung cancer from healthy individuals with sensitivity of 84.1% and specificity of 80%. These findings demonstrated that SAA could be characterized as a biomarker related to pathological stages of lung cancer.
Collapse
Affiliation(s)
- SongWei Dai
- Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Beijing Normal University, Beijing, 100875, China
| | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Bharti A, Ma PC, Salgia R. Biomarker discovery in lung cancer--promises and challenges of clinical proteomics. MASS SPECTROMETRY REVIEWS 2007; 26:451-66. [PMID: 17407130 DOI: 10.1002/mas.20125] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
Lung cancer is a devastating illness with an overall poor prognosis. To effectively address this disease, early detection and novel therapeutics are required. Early detection of lung cancer is challenging, in part because of the lack of adequate tumor biomarkers. The goal of this review is to summarize the knowledge of current biomarkers in lung cancer, with a focus on important serum biomarkers. The current knowledge on the known serum cytokines and tumor biomarkers of lung cancer will be presented. Emerging trends and new findings in the search for novel diagnostic and therapeutic tumor biomarkers using proteomics technologies and platforms are emphasized, including recent advances in mass spectrometry to facilitate tumor biomarker discovery program in lung cancer. It is our hope that validation of these new research platforms and technologies will result in improved early detection, prognostication, and finally the treatment of lung cancer with potential novel molecularly targeted therapeutics.
Collapse
Affiliation(s)
- Ajit Bharti
- Center for Molecular Stress Response Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
| | | | | |
Collapse
|
|
37
|
Chen G, Wang X, Yu J, Varambally S, Yu J, Thomas DG, Lin MY, Vishnu P, Wang Z, Wang R, Fielhauer J, Ghosh D, Giordano TJ, Giacherio D, Chang AC, Orringer MB, El-Hefnawy T, Bigbee WL, Beer DG, Chinnaiyan AM. Autoantibody Profiles Reveal Ubiquilin 1 as a Humoral Immune Response Target in Lung Adenocarcinoma. Cancer Res 2007; 67:3461-7. [PMID: 17409457 DOI: 10.1158/0008-5472.can-06-4475] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
There is considerable evidence that the presence of cancer can elicit a humoral immune response to specific proteins in the host, and these resulting autoantibodies may have potential as noninvasive biomarkers. To characterize the autoantibody repertoire present in the sera of patients with lung adenocarcinoma, we developed a high-density peptide microarray derived from biopanning a lung cancer phage display library. Using a 2,304-element microarray, we interrogated a total of 250 sera from Michigan lung cancer patients and noncancer controls to develop an "autoantibody profile" of lung adenocarcinoma. A set of 22 discriminating peptides derived from a training set of 125 serum samples from lung adenocarcinoma patients and control subjects was found to predict cancer status with 85% sensitivity and 86% specificity in an independent test set of 125 sera. Sequencing of the immunoreactive phage-peptide clones identified candidate humoral immune response targets in lung adenocarcinoma, including ubiquilin 1, a protein that regulates the degradation of several ubiquitin-dependent proteasome substrates. An independent validation set of 122 serum samples from Pittsburgh was examined using two overlapping clones of ubiquilin 1 that showed 0.79 and 0.74 of the area under the receiver operating characteristics curve, respectively. Significantly increased levels of both ubiquilin 1 mRNA and protein, as well as reduced levels of the phosphorylated form of this protein, were detected in lung tumors. Immunofluorescence using anti-ubiquilin 1 antibodies confirmed intracellular expression within tumors cells. These studies indicate that autoantibody profiles, as well as individual candidates, may be useful for the noninvasive detection of lung adenocarcinoma.
Collapse
Affiliation(s)
- Guoan Chen
- Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
38
|
Grizzle WE, Semmes OJ, Bigbee W, Zhu L, Malik G, Oelschlager DK, Manne B, Manne U. the need for review and understanding of SELDI/MALDI mass spectroscopy data prior to analysis. Cancer Inform 2007; 1:86-97. [PMID: 19305634 PMCID: PMC2657646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Abstract
Multiple studies have reported that surface enhanced laser desorption/ionization time of flight mass spectroscopy (SELDI-TOF-MS) is useful in the early detection of disease based on the analysis of bodily fluids. Use of any multiplex mass spectroscopy based approach as in the analysis of bodily fluids to detect disease must be analyzed with great care due to the susceptibility of multiplex and mass spectroscopy methods to biases introduced via experimental design, patient samples, and/or methodology. Specific biases include those related to experimental design, patients, samples, protein chips, chip reader and spectral analysis. Contributions to biases based on patients include demographics (e.g., age, race, ethnicity, sex), homeostasis (e.g., fasting, medications, stress, time of sampling), and site of analysis (hospital, clinic, other). Biases in samples include conditions of sampling (type of sample container, time of processing, time to storage), conditions of storage, (time and temperature of storage), and prior sample manipulation (freeze thaw cycles). Also, there are many potential biases in methodology which can be avoided by careful experimental design including ensuring that cases and controls are analyzed randomly. All the above forms of biases affect any system based on analyzing multiple analytes and especially all mass spectroscopy based methods, not just SELDI-TOF-MS. Also, all current mass spectroscopy systems have relatively low sensitivity compared with immunoassays (e.g., ELISA). There are several problems which may be unique to the SELDI-TOF-MS system marketed by Ciphergen(®). Of these, the most important is a relatively low resolution (±0.2%) of the bundled mass spectrometer which may cause problems with analysis of data. Foremost, this low resolution results in difficulties in determining what constitutes a "peak" if a peak matching approach is used in analysis. Also, once peaks are selected, the peaks may represent multiple proteins. In addition, because peaks may vary slightly in location due to instrumental drift, long term identification of the same peaks may prove to be a challenge. Finally, the Ciphergen(®) system has some "noise" of the baseline which results from the accumulation of charge in the detector system. Thus, we must be very aware of the factors that may affect the use of proteomics in the early detection of disease, in determining aggressive subsets of cancers, in risk assessment and in monitoring the effectiveness of novel therapies.
Collapse
Affiliation(s)
| | | | - William Bigbee
- University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA,Correspondence: William Grizzle,
| | - Liu Zhu
- University of Alabama at Birmingham, Birmingham, AL
| | | | | | - Barkha Manne
- University of Alabama at Birmingham, Birmingham, AL
| | | |
Collapse
|
|
39
|
Jazbec J, Todorovski L, Jereb B. Classification tree analysis of second neoplasms in survivors of childhood cancer. BMC Cancer 2007; 7:27. [PMID: 17270060 PMCID: PMC1802085 DOI: 10.1186/1471-2407-7-27] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2006] [Accepted: 02/02/2007] [Indexed: 11/22/2022] Open
Abstract
Background Reports on childhood cancer survivors estimated cumulative probability of developing secondary neoplasms vary from 3,3% to 25% at 25 years from diagnosis, and the risk of developing another cancer to several times greater than in the general population. Methods In our retrospective study, we have used the classification tree multivariate method on a group of 849 first cancer survivors, to identify childhood cancer patients with the greatest risk for development of secondary neoplasms. Results In observed group of patients, 34 develop secondary neoplasm after treatment of primary cancer. Analysis of parameters present at the treatment of first cancer, exposed two groups of patients at the special risk for secondary neoplasm. First are female patients treated for Hodgkin's disease at the age between 10 and 15 years, whose treatment included radiotherapy. Second group at special risk were male patients with acute lymphoblastic leukemia who were treated at the age between 4,6 and 6,6 years of age. Conclusion The risk groups identified in our study are similar to the results of studies that used more conventional approaches. Usefulness of our approach in study of occurrence of second neoplasms should be confirmed in larger sample study, but user friendly presentation of results makes it attractive for further studies.
Collapse
Affiliation(s)
- Janez Jazbec
- Division of oncology and hematology, Department of Pediatrics, Medical Center, Vrazov trg 1, Ljubljana, Slovenia
| | | | - Berta Jereb
- Institute of Oncology, Zaloška 2, Ljubljana, Slovenia
| |
Collapse
|
|
40
|
Liu H, Lang J, Zhou Q, Shan D, Li Q. Detection of endometriosis with the use of plasma protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Fertil Steril 2007; 87:988-90. [PMID: 17207800 DOI: 10.1016/j.fertnstert.2006.08.095] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2005] [Revised: 08/07/2006] [Accepted: 08/07/2006] [Indexed: 11/29/2022]
Abstract
In this prospective case-control study, we determined the role of surface-enhanced laser desorption and ionization time-of-flight mass spectrometry in the detection of histologically proven endometriosis. In the plasma of the group with endometriosis, there were 20 different protein peaks, and the classifier showed a sensitivity of 87.5% and a specificity of 80% in the diagnosis of endometriosis.
Collapse
|
|
41
|
Wang JX, Yu JK, Wang L, Liu QL, Zhang J, Zheng S. Application of serum protein fingerprint in diagnosis of papillary thyroid carcinoma. Proteomics 2006; 6:5344-9. [PMID: 16941571 DOI: 10.1002/pmic.200500833] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
To find new biomarkers and establish serum protein fingerprint models for early diagnosis and preoperative staging of papillary thyroid carcinoma, we employed SELDI-TOF-MS and bioinformatics tools. A total of 116 samples were analyzed in this study. The first 80 samples were analyzed by SELDI-TOF-MS and two biomarker patterns were identified. Pattern 1 distinguishes patients with papillary thyroid carcinoma from healthy individuals. Pattern 2 distinguishes papillary thyroid carcinoma from benign thyroid nodes. The remaining 29 samples were analyzed on the second day and served as an independent test set. The analysis of this independent test set yielded a specificity of 80.0% and a sensitivity of 88.9% for pattern 1 and a specificity of 80.0% and a sensitivity of 80.0% for pattern 2. Two additional biomarker patterns were identified to distinguish different stages of the papillary thyroid carcinoma (pattern 3) with an accuracy of 77.1% and different pathological types of thyroid carcinoma (pattern 4) with an accuracy of 88.1%. Taken together, the SELDI-TOF-MS technique combined with bioinformatics approaches can not only facilitate the discovery of better biomarkers for papillary thyroid carcinoma but also provide a useful tool for molecular diagnosis in the future.
Collapse
MESH Headings
- Adenocarcinoma, Follicular/blood
- Adenocarcinoma, Follicular/diagnosis
- Adenocarcinoma, Follicular/pathology
- Blood Proteins/metabolism
- Carcinoma, Medullary/blood
- Carcinoma, Medullary/diagnosis
- Carcinoma, Medullary/pathology
- Carcinoma, Papillary/blood
- Carcinoma, Papillary/diagnosis
- Carcinoma, Papillary/pathology
- Humans
- Neoplasm Proteins/blood
- Neoplasm Staging
- Peptide Mapping/methods
- Protein Array Analysis
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Thyroid Neoplasms/blood
- Thyroid Neoplasms/diagnosis
- Thyroid Neoplasms/pathology
Collapse
Affiliation(s)
- Jia-Xiang Wang
- Department of Surgery, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henang Province, P R China
| | | | | | | | | | | |
Collapse
|
|
42
|
Cho WCS. [Research progress in SELDI-TOF MS and its clinical applications]. SHENG WU GONG CHENG XUE BAO = CHINESE JOURNAL OF BIOTECHNOLOGY 2006; 22:871-876. [PMID: 17168305 PMCID: PMC7148935 DOI: 10.1016/s1872-2075(06)60061-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/10/2006] [Accepted: 08/10/2006] [Indexed: 11/17/2022]
Abstract
Proteinchip profiling is a powerful and innovative proteomic technology for the discovery of biomarkers and the development of diagnostic/prognostic assays. On the basis of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), Ciphergen’s proteinchip system offers a single, unified, and high throughput platform for a multitude of proteomic research applications. Proteins are the major functional components of the cell. The study of proteomics helps to better understand the mechanism of a disease. Remarkable findings in disease biomarkers have shed light on the early diagnosis, monitoring, and prognosis of various diseases, especially for cancer. In this paper, the development and technology of SELDI-TOF MS are introduced. The research progress and encouraging research results in malignancies, infectious diseases, neurological diseases, and diabetes mellitus using SELDI-TOF MS are reviewed. This paper concludes by evaluating the pros and cons, and the future perspectives are also expounded.
Collapse
|
|
43
|
Solassol J, Jacot W, Lhermitte L, Boulle N, Maudelonde T, Mangé A. Clinical proteomics and mass spectrometry profiling for cancer detection. Expert Rev Proteomics 2006; 3:311-20. [PMID: 16771703 DOI: 10.1586/14789450.3.3.311] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
A key challenge in the clinical proteomics of cancer is the identification of biomarkers that would enable early detection, diagnosis and monitoring of disease progression to improve long-term survival of patients. Recent advances in proteomic instrumentation and computational methodologies offer a unique chance to rapidly identify these new candidate markers or pattern of markers. The combination of retentate affinity chromatography and mass spectrometry is one of the most interesting new approaches for cancer diagnostics using proteomic profiling. This review presents two technologies in this field, surface-enhanced laser desorption/ionization time-of-flight and Clinprot, and aims to summarize the results of studies obtained with the first of them for the early diagnosis of human cancer. Despite promising results, the use of the proteomic profiling as a diagnostic tool brought some controversies and technical problems, and still requires some efforts to be standardized and validated.
Collapse
Affiliation(s)
- Jérôme Solassol
- Hôpital Arnaud de Villeneuve, Laboratoire de Biologie Cellulaire- INSERM U540, 371 Avenue du Doyen Giraud, 34295 Montpellier Cedex 5, France.
| | | | | | | | | | | |
Collapse
|
|
44
|
Abstract
Proteomics is the study of the entire protein complement of the genome (the proteome) in a biological system. Proteomic studies require a multidisciplinary approach and have only been practical with the convergence of technical and methodologic improvements including the following: advances in mass spectrometry and genomic sequencing that now permit the identification and relative quantization of small amounts (femtomole) of nearly any single protein; new methods in gel electrophoresis that allow the detection of subtle changes in protein expression, including posttranslational modifications; automation and miniaturization that permit high-throughput analysis of clinical samples; and new bioinformatics and computational methods that facilitate analysis and interpretation of the abundant data that are generated by proteomics experiments. This convergence makes proteomics studies practical for pulmonary researchers using BAL fluid, lung tissue, blood, and exhaled breath condensates, and will facilitate the research of complex, multifactorial lung diseases such as acute lung injury and COPD. This review describes how proteomics experiments are conducted and interpreted, their limitations, and how proteomics has been used in clinical pulmonary medicine.
Collapse
Affiliation(s)
- Russell P Bowler
- Department of Medicine, University of Colorado Health Sciences Center, Denver, 80206, USA.
| | | | | |
Collapse
|
|
45
|
Miles AK, Matharoo-Ball B, Li G, Ahmad M, Rees RC. The identification of human tumour antigens: Current status and future developments. Cancer Immunol Immunother 2006; 55:996-1003. [PMID: 16408215 PMCID: PMC11029826 DOI: 10.1007/s00262-005-0115-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2005] [Accepted: 12/10/2005] [Indexed: 11/25/2022]
Abstract
The biggest challenge facing us today in cancer control and prevention is the identification of novel biomarkers for detection and improved therapeutic interventions to reduce mortality and morbidity rates. Biomarkers are important indicators to inform us of the physiological state of the cell at a specific time. It is now clear that malignant transformation occurs by changes in cellular DNA and protein expression with subsequent clonal proliferation of the altered cells. The affected genes and their expressed protein products or biomarkers are those involved in the normal growth and maintenance of the cancerous cells. These biomarkers could prove pivotal for the identification of early cancer and people at risk of developing cancer. Altered proteins or changes in gene expression in malignant cells may lead to the expression of tumour antigens recognised by host immune system. In this review we discuss current research into the molecular technologies making possible the global genomic-wide analysis of changes in DNA (genotyping), RNA expression (transcriptomics) and protein expression (proteomics) that have accelerated the rate of new biomarker/tumour antigen discovery. To gain a comprehensive understanding of the physiology and pathophysiology of cancer an approach that harmoniously integrates the various 'omic' platforms are key to unraveling the complexity 'needle-in-a-haystack' quality of biomarker/tumour antigen discovery.
Collapse
Affiliation(s)
- Amanda K. Miles
- School of Biomedical and Natural Sciences, Nottingham Trent University, Clifton Lane, Clifton, NG11 8NS Nottingham, UK
| | - Balwir Matharoo-Ball
- School of Biomedical and Natural Sciences, Nottingham Trent University, Clifton Lane, Clifton, NG11 8NS Nottingham, UK
| | - Geng Li
- School of Biomedical and Natural Sciences, Nottingham Trent University, Clifton Lane, Clifton, NG11 8NS Nottingham, UK
| | - Murrium Ahmad
- School of Biomedical and Natural Sciences, Nottingham Trent University, Clifton Lane, Clifton, NG11 8NS Nottingham, UK
| | - Robert C. Rees
- School of Biomedical and Natural Sciences, Nottingham Trent University, Clifton Lane, Clifton, NG11 8NS Nottingham, UK
| |
Collapse
|
|
46
|
Ciordia S, de Los Ríos V, Albar JP. Contributions of advanced proteomics technologies to cancer diagnosis. Clin Transl Oncol 2006; 8:566-80. [PMID: 16952845 DOI: 10.1007/s12094-006-0062-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The ability of Medicine to effectively treat and cure cancer is directly dependent on their capability to detect cancers at their earliest stages. The advent of proteomics has brought with it the hope of discovering novel biomarkers in the early phases of tumorigenesis that can be used to diagnose diseases, predict susceptibility, and monitor progression. This discipline incorporates technologies that can be applied to complex biosystems such as serum and tissue in order to characterize the content of, and changes in, the proteome induced by physiological changes, benign or pathologic. These tools include 2-DE, 2D-DIGE, ICAT, protein arrays, MudPIT and mass spectrometries including SELDI-TOF. The application of these tools has assisted to uncover molecular mechanisms associated with cancer at the global level and may lead to new diagnostic tests and improvements in therapeutics. In this review these approaches are evaluated in the context of their contribution to cancer biomarker discovery. Particular attention is paid to the promising contribution of the ProteinChip/SELDI-TOF platform as a revolutionary approach in proteomic patterns analysis that can be applied at the bedside for discovering protein profiles that distinguish disease and disease-free states with high sensitivity and specificity. Understanding the basic concepts and tools used will illustrate how best to apply these technologies for patient benefit for the early cancer detection and improved patient care.
Collapse
Affiliation(s)
- Sergio Ciordia
- Proteomics Facility, Centro Nacional de Biotecnología-CSIC, Universidad Autónoma, Madrid, Spain
| | | | | |
Collapse
|
|
47
|
Lo WY, Tsai MH, Tsai Y, Hua CH, Tsai FJ, Huang SY, Tsai CH, Lai CC. Identification of over-expressed proteins in oral squamous cell carcinoma (OSCC) patients by clinical proteomic analysis. Clin Chim Acta 2006; 376:101-7. [PMID: 16889763 DOI: 10.1016/j.cca.2006.06.030] [Citation(s) in RCA: 105] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2006] [Revised: 06/12/2006] [Accepted: 06/26/2006] [Indexed: 10/24/2022]
Abstract
BACKGROUND Oral cancer is a worldwide problem. It is a universal aggressive disease in the population of smoking and drinking. The oral cancer mortality has been ranked 5th place in Taiwan in male cancer patients. A number of protein markers for oral cancer are still not applicable in large populations. Proteomic technologies provide excellent tools for rapid screening of a large number of potential biomarkers in malignant cells. METHOD Proteomics and real-time quantitative RT-PCR were used to analyze over-expressed proteins in 10 OSCC patients. RESULT Forty-one proteins were identified as commonly over-expressed in OSCC tissues. In OSCC tissues, alphaB-crystallin, tropomyosin 2, myosin light chain 1, heat shock protein 27 (HSP27), stratifin, thioredoxin-dependent peroxide reductase, flavin reductase, vimentin, rho GDP-dissociation inhibitor 2 (rho GDI-2), glutathione S-transferase Pi (GST-pi) and superoxide dismutase [Mn] (MnSOD) were significantly over-expressed (an average of 7.2, 6.0, 5.7, 4.3, 3.6, 3.4, 3.0, 3.0, 2.6, 2.5, 2.1-fold, respectively). In real-time quantitative RT-PCR analysis, the gene expressions of alphaB-crystallin, HSP27 and MnSOD were also increased in the cancer tissues, consistent with proteomic results. CONCLUSION The identified proteins in this experiment may be used in future studies of carcinogenesis or as diagnostic markers and therapeutic targets for OSCC.
Collapse
Affiliation(s)
- Wan-Yu Lo
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Scarlett CJ, Smith RC, Saxby A, Nielsen A, Samra JS, Wilson SR, Baxter RC. Proteomic classification of pancreatic adenocarcinoma tissue using protein chip technology. Gastroenterology 2006; 130:1670-1678. [PMID: 16697731 DOI: 10.1053/j.gastro.2006.02.036] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2005] [Accepted: 02/01/2006] [Indexed: 01/02/2023]
Abstract
BACKGROUND & AIMS Pancreatic adenocarcinoma is a most devastating cancer that presents late and is rapidly progressive. This study aimed to identify unique, tissue-specific protein biomarkers capable of differentiating pancreatic adenocarcinoma (PC) from adjacent uninvolved pancreatic tissue (AP), benign pancreatic disease (B), and nonmalignant tumor tissue (NM). METHODS Tissue samples representing PC (n = 31), AP (n = 44), and B (n = 19) tissue were analyzed on hydrophobic protein chip arrays by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Training models were developed using logistic regression and validated using the 10-fold cross-validation approach. RESULTS The hydrophobic protein chip array revealed 13 protein peaks differentially expressed between PC and AP (receiver operating characteristic [ROC] area under the curve [AUC], 0.64-0.85), 8 between PC and B (ROC AUC, 0.67-0.78), and 12 between PC and NM tissue (ROC AUC, 0.63-0.81). Logistic regression and cross-validation identified overlapping panels of peaks to develop a training model that distinguished PC from AP (77.4% sensitivity, 84.1% specificity), B (83.9% sensitivity, 78.9% specificity), and NM tissue (58.1% sensitivity, 90.5% specificity). The final panels selected correctly classified 80.6% of PC and 88.6% of AP samples (ROC AUC, 0.92), 93.5% of PC and 89.5% of B samples (ROC AUC, 0.99), and 71.0% of PC and 92.1% of NM samples (ROC AUC, 0.91). CONCLUSIONS This study used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to discover a number of protein panels that can distinguish effectively between pancreatic adenocarcinoma, benign, and adjacent pancreatic tissue. Identification of these proteins will add to our understanding of the biology of pancreatic cancer. Furthermore, these protein panels may have important diagnostic implications.
Collapse
Affiliation(s)
- Christopher J Scarlett
- Department of Surgery, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | | | | | | | | | | | | |
Collapse
|
|
49
|
Manne U, Srivastava RG, Srivastava S. Recent advances in biomarkers for cancer diagnosis and treatment. Drug Discov Today 2006; 10:965-76. [PMID: 16023055 DOI: 10.1016/s1359-6446(05)03487-2] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
With the availability of new technologies and the increased interest of medical practitioners to use molecular biomarkers in early detection and diagnosis, and in the prediction of therapeutic treatment efficacy and clinical outcomes, the academic and research institutions, as well as the pharmaceutical industry, have increased their efforts to develop novel molecular biomarkers for several human diseases, including cancer. The identification of molecular biomarkers also enables the development of a new generation of diagnostic products and to integrate diagnostics and therapeutics. This integrated approach will aid in 'individualizing' the medical practice. Here, we address issues related to the development of biomarkers, novel technological platforms used for drug development, future technologies and strategies for validating biomarkers for their clinical utility.
Collapse
|
|
50
|
Turhani D, Krapfenbauer K, Thurnher D, Langen H, Fountoulakis M. Identification of differentially expressed, tumor-associated proteins in oral squamous cell carcinoma by proteomic analysis. Electrophoresis 2006; 27:1417-23. [PMID: 16568407 DOI: 10.1002/elps.200500510] [Citation(s) in RCA: 106] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Oral squamous cellular carcinoma is a malignant tumor with poor prognosis and therefore the discovery of early markers to discriminate malignant from normal cells would be of critical importance in clinical diagnosis. Subcellular fractions from oral squamous cell carcinoma (OSCC) and control samples, enriched in mitochondrial and cytosolic proteins, were analyzed by 2-DE, followed by MALDI-TOF-MS. Twenty proteins showed altered expression levels in OSCC; 14 were up- and 6 were down-regulated in comparison with the control samples. For 11 proteins, cofilin, C-reactive protein precursor, creatine kinase m-chain, fatty acid-binding protein, keratin type II, myosin light chain 2 and 3, nucleoside diphosphate kinase A, phosphoglycerate mutase 1, plakoglobulin, and retinoic acid-binding protein II, it is shown for the first time that they are differentially expressed in OSCC. Proteins with highly up-regulated levels may be of interest as potential diagnostic markers and consequently of clinical interest.
Collapse
Affiliation(s)
- Dritan Turhani
- Department of Cranio-Maxillofacial and Oral Surgery, University of Vienna, Vienna, Austria
| | | | | | | | | |
Collapse
|