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1
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Rungkamoltip P, Roytrakul S, Navakanitworakul R. MALDI-TOF MS Analysis of Serum Peptidome Patterns in Cervical Cancer. Biomedicines 2023; 11:2327. [PMID: 37626823 PMCID: PMC10452062 DOI: 10.3390/biomedicines11082327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/16/2023] [Accepted: 08/18/2023] [Indexed: 08/27/2023] Open
Abstract
BACKGROUND Cervical cancer is the fourth most common cancer among females worldwide. Identifying peptide patterns discriminating healthy individuals from those with diseases has gained interest in the early detection of cancers. Our study aimed to determine signature peptide patterns for cervical cancer screening. METHODS Our study focused on the serum peptidome analysis of 83 healthy women and 139 patients with cervical cancer. All spectra derived from matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were analyzed using FlexAnalysis 3.0 and ClinProTools 2.2 software. RESULTS In the mass range of 1000-10,000 Da, the total average spectra were represented as the signature pattern. Principal component analysis showed that all the groups were separately distributed. Furthermore, the peaks at m/z 1466.91, 1898.01, 3159.09, and 4299.40 significantly differed among the investigated groups (Wilcoxon/Kruskal-Wallis test and ANOVA, p < 0.001). CONCLUSIONS Laboratory-based rapid mass spectrometry showed that serum peptidome patterns could serve as diagnostic tools for diagnosing cervical cancer; however, verification through larger cohorts and association with clinical data are required, and the use of externally validated samples, such as patients with other types of cancers, should be investigated to validate the specific peptide patterns.
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Affiliation(s)
- Phetploy Rungkamoltip
- Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand;
| | - Sittiruk Roytrakul
- Proteomic Research Laboratory, National Center for Genetic Engineering and Biotechnology, Thailand Science Park, Pathum Thani 12120, Thailand;
| | - Raphatphorn Navakanitworakul
- Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand;
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2
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Plasma proteomics-based identification of novel biomarkers in early gastric cancer. Clin Biochem 2020; 76:5-10. [PMID: 31765635 DOI: 10.1016/j.clinbiochem.2019.11.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 10/27/2019] [Accepted: 11/02/2019] [Indexed: 12/18/2022]
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3
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Li H, Popp R, Borchers CH. Affinity-mass spectrometric technologies for quantitative proteomics in biological fluids. Trends Analyt Chem 2017. [DOI: 10.1016/j.trac.2017.02.011] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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4
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Wan QS, Zhang KH. Noninvasive detection of gastric cancer. Tumour Biol 2016; 37:11633-11643. [PMID: 27381515 DOI: 10.1007/s13277-016-5129-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 06/29/2016] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer (GC) is the fifth most common cancer and the third common cause of cancer death worldwide. Endoscopy is the most effective method for GC screening, but its application is limited by the invasion. Therefore, continuous efforts have been made to develop noninvasive methods for GC detection and promising results have been reported. Here, we review the advances in GC detection by protein and nucleic acid tumor markers, circulating tumor cells, and tumor-associated autoantibodies in peripheral blood. Some potential new noninvasive methods for GC detection are also reviewed, including exhaled breath analysis, blood spectroscopy analysis and molecular imaging.
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Affiliation(s)
- Qin-Si Wan
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, 17 Yongwai Zheng Street, Nanchang, Jiangxi, 330006, China
| | - Kun-He Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, 17 Yongwai Zheng Street, Nanchang, Jiangxi, 330006, China.
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Beeharry MK, Liu WT, Yan M, Zhu ZG. New blood markers detection technology: A leap in the diagnosis of gastric cancer. World J Gastroenterol 2016; 22:1202-1212. [PMID: 26811658 PMCID: PMC4716031 DOI: 10.3748/wjg.v22.i3.1202] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2015] [Revised: 09/28/2015] [Accepted: 11/24/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is still one of the malignant tumors with high morbidity and mortality in the world, with a 5-year survival rate of less than 30%. GC is often either asymptomatic or causes only nonspecific symptoms in its early stages, whereas when the symptoms manifest, the cancer has usually reached an advanced stage, which is one of the main causes of its relatively poor prognosis. Hence, the main focus of GC research has been on discovering new tools and technology to predict, screen and diagnose GC at an early stage which would prompt early treatment. With the tremendous advances in the OMICS technology, serum proteomics has been in the limelight of cancer research over the last few decades and has steered the development of several methods helping to understand the mechanisms underlying gastric carcinogenesis, resulting in the identification of a large number of molecular targets such as circulating tumor cells (CTCs), cell free DNA (cfDNA) and cell tumor DNA (ctDNA) and their sub-molecular components such as miRNA, that show great promise as GC biomarkers. In this review, we are underlying the recent breakthroughs about new blood markers technology for GC while scrutinizing the potential clinical use of CTCs, cfDNA, ctDNA and the role of the methylation of their sub-molecular components in the pathogenesis, diagnosis and management of GC.
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6
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Kalniņa Z, Meistere I, Kikuste I, Tolmanis I, Zayakin P, Linē A. Emerging blood-based biomarkers for detection of gastric cancer. World J Gastroenterol 2015; 21:11636-11653. [PMID: 26556992 PMCID: PMC4631966 DOI: 10.3748/wjg.v21.i41.11636] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2015] [Revised: 07/08/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Early detection and efficient monitoring of tumor dynamics are prerequisites for reducing disease burden and mortality, and for improving the management of patients with gastric cancer (GC). Blood-based biomarker assays for the detection of early-stage GC could be of great relevance both for population-wide or risk group-based screening programs, while circulating biomarkers that reflect the genetic make-up and dynamics of the tumor would allow monitoring of treatment efficacy, predict recurrences and assess the genetic heterogeneity of the tumor. Recent research to identify blood-based biomarkers of GC has resulted in the identification of a wide variety of cancer-associated molecules, including various proteins, autoantibodies against tumor associated antigens, cell-free DNA fragments, mRNAs and various non-coding RNAs, circulating tumor cells and cancer-derived extracellular vesicles. Each type of these biomarkers provides different information on the disease status, has different advantages and disadvantages, and distinct clinical usefulness. In the current review, we summarize the recent developments in blood-based GC biomarker discovery, discuss the origin of various types of biomarkers and their clinical usefulness and the technological challenges in the development of biomarker assays for clinical use.
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7
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A Review: Proteomics in Nasopharyngeal Carcinoma. Int J Mol Sci 2015; 16:15497-530. [PMID: 26184160 PMCID: PMC4519910 DOI: 10.3390/ijms160715497] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2015] [Revised: 06/08/2015] [Accepted: 07/01/2015] [Indexed: 12/24/2022] Open
Abstract
Although radiotherapy is generally effective in the treatment of major nasopharyngeal carcinoma (NPC), this treatment still makes approximately 20% of patients radioresistant. Therefore, the identification of blood or biopsy biomarkers that can predict the treatment response to radioresistance and that can diagnosis early stages of NPC would be highly useful to improve this situation. Proteomics is widely used in NPC for searching biomarkers and comparing differentially expressed proteins. In this review, an overview of proteomics with different samples related to NPC and common proteomics methods was made. In conclusion, identical proteins are sorted as follows: Keratin is ranked the highest followed by such proteins as annexin, heat shock protein, 14-3-3σ, nm-23 protein, cathepsin, heterogeneous nuclear ribonucleoproteins, enolase, triosephosphate isomerase, stathmin, prohibitin, and vimentin. This ranking indicates that these proteins may be NPC-related proteins and have potential value for further studies.
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8
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Chai Y, Wang J, Gao Y, Wang T, Shi F, Su J, Yang Y, Zhou X, Song L, Liu Z. Identification of biomarkers for radiation-induced acute intestinal symptoms (RIAISs) in cervical cancer patients by serum protein profiling. JOURNAL OF RADIATION RESEARCH 2015; 56:134-40. [PMID: 25256248 PMCID: PMC4572598 DOI: 10.1093/jrr/rru081] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 07/22/2014] [Accepted: 08/21/2014] [Indexed: 05/11/2023]
Abstract
Radiation-induced acute intestinal symptoms (RIAISs) are the most frequent complication of radiotherapy that causes great pain and limits the treatment efficacy. The aim of this study was to identify serum biomarkers of RIAISs in cervical cancer patients by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Serum samples were collected from 66 cervical cancer patients prior to pelvic radiotherapy. In our study, RIAISs occurred in 11 patients. An additional 11 patients without RIAISs were selected as controls, whose age, stage, histological type and treatment methods were matched to RIAISs patients. The 22 sera were subsequently analyzed by SELDI-TOF MS, and the resulting protein profiles were evaluated to identify biomarkers using appropriate bioinformatics tools. Comparing the protein profiles of serum samples from the RIAIS group and the control group, it was found that 22 protein peaks were significantly different (P < 0.05), and six of these peaks with mass-to-charge (m/z) ratios of 7514.9, 4603.94, 6887.41, 2769.21, 3839.72 and 4215.7 were successfully identified. A decision tree model of biomarkers was constructed based on three biomarkers (m/z 1270.88, 1503.23 and 7514.90), which separated RIAIS-affected patients from the control group with an accuracy of 81%. This study suggests that serum proteomic analysis by SELDI-TOF MS can identify cervical cancer patients that are susceptible to RIAISs prior to pelvic radiotherapy.
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Affiliation(s)
- Yanlan Chai
- Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P. R. China
| | - Juan Wang
- Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P. R. China
| | - Ying Gao
- Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P. R. China
| | - Tao Wang
- Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P. R. China
| | - Fan Shi
- Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P. R. China
| | - Jin Su
- Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P. R. China
| | - Yunyi Yang
- Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P. R. China
| | - Xi Zhou
- Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P. R. China Renmin Hospital, Hubei University of Medicine, Hubei 442000, P. R. China
| | - Liping Song
- Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P. R. China
| | - Zi Liu
- Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P. R. China
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9
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Tsai MM, Wang CS, Tsai CY, Chi HC, Tseng YH, Lin KH. Potential prognostic, diagnostic and therapeutic markers for human gastric cancer. World J Gastroenterol 2014; 20:13791-13803. [PMID: 25320517 PMCID: PMC4194563 DOI: 10.3748/wjg.v20.i38.13791] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 04/18/2014] [Accepted: 05/26/2014] [Indexed: 02/06/2023] Open
Abstract
The high incidence of gastric cancer (GC) and its consequent mortality rate severely threaten human health. GC is frequently not diagnosed until a relatively advanced stage. Surgery is the only potentially curative treatment. Thus, early screening and diagnosis are critical for improving prognoses in patients with GC. Gastroscopy with biopsy is an appropriate method capable of aiding the diagnosis of specific early GC tumor types; however, the stress caused by this method together with it being excessively expensive makes it difficult to use it as a routine method for screening for GC on a population basis. The currently used tumor marker assays for detecting GC are simple and rapid, but their use is limited by their low sensitivity and specificity. In recent years, several markers have been identified and tested for their clinical relevance in the management of GC. Here, we review the serum-based tumor markers for GC and their clinical significance, focusing on discoveries from microarray/proteomics research. We also review tissue-based GC tumor markers and their clinical application, focusing on discoveries from immunohistochemical research. This review provides a brief description of various tumor markers for the purposes of diagnosis, prognosis and therapeutics, and we include markers already in clinical practice and various forthcoming biomarkers.
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Liquid chromatography-mass spectrometry based serum peptidomic approach for renal clear cell carcinoma diagnosis. J Pharm Biomed Anal 2014; 100:175-183. [PMID: 25168216 DOI: 10.1016/j.jpba.2014.07.028] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Revised: 06/30/2014] [Accepted: 07/24/2014] [Indexed: 11/23/2022]
Abstract
Serum peptidomic approach was applied to investigate the peptidomic signature and discover the clinical biomarkers and biomarker patterns for RCC patients. The holistic orthogonal partial least-squares-discriminant analysis (OPLS-DA) based on qualified profile data successfully classified RCC patients from healthy controls, showing 100% sensitivity and specificity. Following critical criteria, several peptides presenting significant differences in serum level were picked out. The unsupervised hierarchical cluster analysis on those peptides was performed, showing 100% sensitivity and 93.3% specificity for RCC diagnosis regarding the present samples. Besides, receiver-operating characteristic (ROC) analysis was applied on single peptide biomarkers, with four peptides showing excellent predictive power. Among them, IYQLNSKLV and AGISMRSGDSPQD are reported for the first time for cancer detection.
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11
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An J, Tang C, Wang N, Liu Y, Guo W, Li X, Wang Z, He K, Liu X. [Preliminary study of MALDI-TOF mass spectrometry-based screening of patients with the NSCLC serum-specific peptides]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2014; 16:233-9. [PMID: 23676979 PMCID: PMC6000603 DOI: 10.3779/j.issn.1009-3419.2013.05.04] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
背景与目的 早期诊断是提高肺癌生存率的关键，传统的肺癌诊断技术仍存在一定局限性。鉴于近年来以质谱为核心技术的肿瘤蛋白组学在癌症诊断方面的初步研究，本研究探索性应用基质辅助激光解析电离飞行时间质谱（matrix assisted laser desorption ionization-time of flight-mass spectrometry, MALDI-TOF-MS）分析非小细胞肺癌（non-small cell lung cancer, NSCLC）患者和健康人群的血清差异多肽，以建立NSCLC的血清分类模型。 方法 将年龄和性别匹配的133例NSCLC患者和132例健康者血清标本按照3:1的比例随机分为两组：训练组由100例NSCLC患者和100例健康者血清标本组成，用以建立分类模型；测试组由33例NSCLC患者和32例健康者血清标本组成，用以验证模型。采用铜离子鳌合纳米磁珠提取血清多肽、MALDI-TOF-MS技术检测得到质谱图。ClinProToolsTM统计软件分析训练组NSCLC患者与健康者之间的多肽图谱，从中筛选出一组差异多肽并建立分类模型，最后用测试组对模型进行盲样验证。 结果 在训练组中观察到血清质荷比（m/z）在1, 000 Da-10, 000 Da范围内有131个差异多肽信号峰，在此范围内共得到14个有统计学意义的差异多肽峰（P < 0.000, 001; AUC≥0.9），其中NSCLC患者与健康者相比，表达上调的多肽有2个，表达下调的有12个，由统计软件筛选出3个多肽峰（7, 478.59 Da、2, 271.44 Da、4, 468.38 Da）建立分类模型，然后对测试组进行验证，其盲样验证敏感性100%，特异性96.9%，准确率98.5%。 结论 本组研究显示NSCLC患者与健康人群的血清多肽存在差异，应用MALDI-TOF-MS技术可建立NSCLC的血清多肽分类模型且小规模验证具有较好的敏感性和特异性，希望大规模验证模型，并与传统诊断方法对照或结合，进而尝试建立一种新的NSCLC早期诊断模式。
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Affiliation(s)
- Juan An
- Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China
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He CZ, Zhang KH. Serum protein and genetic tumor markers of gastric carcinoma. Asian Pac J Cancer Prev 2014; 14:3437-42. [PMID: 23886124 DOI: 10.7314/apjcp.2013.14.6.3437] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
The high incidence of gastric cancer and consequent mortality pose severe threats to human health. Early screening, diagnosis and treatment are the key to improve the prognosis of the patients with gastric cancer. Gastroscopy with biopsy is an efficient method for the diagnosis of early gastric cancer, but the associated discomfort and high cost make it difficult to be a routine method for screening gastric cancer. Serum tumor marker assay is a simple and practical method for detection of gastric cancer, but it is limited by poor sensitivity and specificity. Therefore, people have been looking for novel serum markers of gastric cancer in recent years. Here we review the novel serum tumor markers of gastric cancer and their diagnostic significance, focusing on the discoveries from serum proteomics analyses and epigenetics researches.
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Affiliation(s)
- Chao-Zhu He
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, Nanchang, China.
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Gopal G, Shirley S, Raja UM, Rajkumar T. Endo-sulfatase Sulf-1 protein expression is down-regulated in gastric cancer. Asian Pac J Cancer Prev 2012; 13:641-6. [PMID: 22524839 DOI: 10.7314/apjcp.2012.13.2.641] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
In our recent report on gene expression in gastric cancer we identified the endo-sulfatase Sulf-1 gene to be up-regulated in gastric tumors relative to apparently normal (AN), and paired normal (PN) gastric tissue samples. In the present report we investigate the protein expression levels of Sulf-1 gene in gastric tumors, AN and PN samples using tissue microarray (TMA) and immunohistochemistry. Expression data was collected from two sets of TMA's containing replicate sections of tissue samples. Scoring data from TMA set-1 revealed a significant difference in Sulf-1 immunoreactivity between tumors and "normals" (PN and AN) (p-value = 0.001928). Also, Sulf-1 expression in tumors was also significantly different from either PN (p-value = 0.019) or AN (p-value = 0.006) samples. Similar results were obtained from analysis of scoring data from the second set of arrays. Comparison of mRNA expression and protein expression in gastric tumor tissues revealed that in 6/20 (30%) tumor samples showed up-regulated protein expression concordant with over-expression of mRNA. However, a discord with mRNA being over-expressed relative to down regulated protein expression was observed in majority 14/20 (70%) of tumor samples. Our study indicates down regulation of Sulf-1 protein expression in gastric tumors relative to PN and AN samples which is discordant with mRNA over-expression seen in tumors.
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Affiliation(s)
- Gopisetty Gopal
- Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India
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Identification of Potential Markers Related to Neoadjuvant Chemotherapy Sensitivity of Breast Cancer by SELDI-TOF MS. Appl Biochem Biotechnol 2011; 166:753-63. [DOI: 10.1007/s12010-011-9464-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2011] [Accepted: 11/15/2011] [Indexed: 11/27/2022]
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Deng C, Lin M, Hu C, Li Y, Gao Y, Cheng X, Zhang F, Dong M, Li Y. Exploring serological classification tree model of active pulmonary tuberculosis by magnetic beads pretreatment and MALDI-TOF MS analysis. Scand J Immunol 2011; 74:397-405. [PMID: 21668462 DOI: 10.1111/j.1365-3083.2011.02590.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Pulmonary tuberculosis (TB) is an infectious disease disturbing status of public health, and accurate diagnosis of TB would effectively help control the disturbance. Our study tried to establish a classification tree model that distinguished active TB from non-TB individuals. We used matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) combined with weak cationic exchange (WCX) magnetic beads to analyse 178 serum samples containing 75 patients with active TB and 103 non-TB individuals (43 patients with common pulmonary diseases and 60 healthy controls). Samples were randomly divided into a training set and a test set. Statistical softwares were applied to construct this model. An amount of 48 differential expressed peaks (P < 0.05) were identified by the training set, and our model was set up by three of them, m/z 7626, 8561 and 8608. This model can discriminate patients with active TB from patients with non-TB with a sensitivity of 98.3% and a specificity of 84.4%. The test set was used to verify the performance, which demonstrated good sensitivity and specificity: 85.7% and 83.3%, respectively. Differential expressed peaks between smear-positive and smear-negative active TB also have been analysed. It came out that m/z 8561 and 8608 not only acted as vital factors in the pathogenesis of active TB but also played an important role in regulating different active TB status. In conclusion, MALDI-TOF MS combined with WCX magnetic beads was a powerful technology for constructing classification tree model, and the model we built could serve as a potential diagnostic tool for active TB.
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Affiliation(s)
- C Deng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Ikeda A, Nishiumi S, Shinohara M, Yoshie T, Hatano N, Okuno T, Bamba T, Fukusaki E, Takenawa T, Azuma T, Yoshida M. Serum metabolomics as a novel diagnostic approach for gastrointestinal cancer. Biomed Chromatogr 2011; 26:548-58. [PMID: 21773981 DOI: 10.1002/bmc.1671] [Citation(s) in RCA: 117] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2011] [Revised: 05/29/2011] [Accepted: 06/06/2011] [Indexed: 12/22/2022]
Abstract
Conventional tumor markers are unsuitable for detecting carcinoma at an early stage and lack clinical efficacy and utility. In this study, we attempted to investigate the differences in serum metabolite profiles of gastrointestinal cancers and healthy volunteers using a metabolomic approach and searched for sensitive and specific metabolomic biomarker candidates. Human serum samples were obtained esophageal (n = 15), gastric (n = 11), and colorectal (n = 12) cancer patients and healthy volunteers (n = 12). A model for evaluating metabolomic biomarker candidates was constructed using multiple classification analysis, and the results were assessed with receiver operating characteristic curves. Among the 58 metabolites, the levels of nine, five and 12 metabolites were significantly changed in the esophageal, gastric and colorectal cancer patients, respectively, compared with the healthy volunteers. Multiple classification analysis revealed that the variations in the levels of malonic acid and L-serine largely contributed to the separation of esophageal cancer; gastric cancer was characterized by changes in the levels of 3-hydroxypropionic acid and pyruvic acid; and L-alanine, glucuronoic lactone and L-glutamine contributed to the separation of colorectal cancer. Our approach revealed that some metabolites are more sensitive for detecting gastrointestinal cancer than conventional biomarkers. Our study supports the potential of metabolomics as an early diagnostic tool for cancer.
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Affiliation(s)
- Atsuki Ikeda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
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Dudley E, Hässler F, Thome J. Profiling for novel proteomics biomarkers in neurodevelopmental disorders. Expert Rev Proteomics 2011; 8:127-36. [PMID: 21329432 DOI: 10.1586/epr.10.97] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Protein biomarker discovery from biological fluids, such as serum, has been widely applied to disorders such as cancer and has more recently also been utilized in neuro-psychiatric disorders with relatively clear biological causes, such as Alzheimer's disease and schizophrenia. The application of the associated technologies for the identification of protein biomarker signatures in neurodevelopmental disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder, is comparatively less well established. The aim of this article is to provide an overview of the various protocols available for such analysis, discuss reports in which these techniques have been previously applied in biomarker discovery/validation in neurodevelopmental disorders, and consider the future development of this area of research.
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Affiliation(s)
- Ed Dudley
- Institute of Mass Spectrometry, School of Medicine, Swansea University, Swansea, UK
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Diao L, Clarke CH, Coombes KR, Hamilton SR, Roth J, Mao L, Czerniak B, Baggerly KA, Morris JS, Fung ET, Bast RC. Reproducibility of SELDI Spectra Across Time and Laboratories. Cancer Inform 2011; 10:45-64. [PMID: 21552492 PMCID: PMC3085423 DOI: 10.4137/cin.s6438] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited.The reproducibility of mass spectrometry (MS) data collected using surface enhanced laser desorption/ionization-time of flight (SELDI-TOF) has been questioned. This investigation was designed to test the reproducibility of SELDI data collected over time by multiple users and instruments. Five laboratories prepared arrays once every week for six weeks. Spectra were collected on separate instruments in the individual laboratories. Additionally, all of the arrays produced each week were rescanned on a single instrument in one laboratory. Lab-to-lab and array-to-array variability in alignment parameters were larger than the variability attributable to running samples during different weeks. The coefficient of variance (CV) in spectrum intensity ranged from 25% at baseline, to 80% in the matrix noise region, to about 50% during the exponential drop from the maximum matrix noise. Before normalization, the median CV of the peak heights was 72% and reduced to about 20% after normalization. Additionally, for the spectra from a common instrument, the CV ranged from 5% at baseline, to 50% in the matrix noise region, to 20% during the drop from the maximum matrix noise. Normalization reduced the variability in peak heights to about 18%. With proper processing methods, SELDI instruments produce spectra containing large numbers of reproducibly located peaks, with consistent heights.
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Affiliation(s)
- Lixia Diao
- Departments of Bioinformatics and Computational Biology
| | | | | | | | | | - Li Mao
- Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore MD 21201
| | | | | | - Jeffrey S. Morris
- Biostatistics, the University of Texas M.D. Anderson Cancer Center, Houston TX 77030 USA
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Kraljevic Pavelic S, Sedic M, Bosnjak H, Spaventi S, Pavelic K. Metastasis: new perspectives on an old problem. Mol Cancer 2011; 10:22. [PMID: 21342498 PMCID: PMC3052211 DOI: 10.1186/1476-4598-10-22] [Citation(s) in RCA: 127] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2010] [Accepted: 02/22/2011] [Indexed: 12/23/2022] Open
Abstract
Many hypotheses have been postulated to explain the intricate nature of the metastatic process, but none of them completely accounted for the actual biological and clinical observations. Consequently, metastasis still remains an open issue with only few metastasis-inducing proteins experimentally validated so far. Recently proposed novel metastatic model, where serial and parallel metastatic processes are adequately integrated, might help to bridge the current gap between experimental results and clinical observations. In addition, the identification, isolation and molecular characterization of cancer stem cells, a population of the cells within the tumour mass able to proliferate, self-renew and induce tumorigenesis, will shed new light on the complex molecular events mediating metastasis, invasion and resistance to therapy. Understanding the molecular basis of these tumour characteristics will usher in a new age of individualized cancer therapy. In this review article, we will provide a current overview of molecular mechanisms underpinning metastasis, and discuss recent findings in this field obtained by global molecular profiling strategies such as proteomics.
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Bones J, Byrne JC, O'Donoghue N, McManus C, Scaife C, Boissin H, Nastase A, Rudd PM. Glycomic and glycoproteomic analysis of serum from patients with stomach cancer reveals potential markers arising from host defense response mechanisms. J Proteome Res 2011; 10:1246-65. [PMID: 21142185 DOI: 10.1021/pr101036b] [Citation(s) in RCA: 108] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Despite the reduced incidence of gastric cancer in the developed world, a diagnosis of stomach carcinoma still carries a poor prognosis due to the asymptomatic nature of the disease in the early stages, subsequent advanced stage diagnosis, and a low 5 year survival rate. Endoscopy remains the primary standard for diagnosis of stomach carcinoma and the current marker, carbohydrate antigen 19-9 (CA19-9) lacks the levels of sensitivity and specificity required in order to make it clinically useful for diagnostic monitoring. Therefore, there is a current need for additional markers to improve the diagnostic accuracy for the early stages of stomach cancer. Together, glycomic, proteomic, and glycoproteomic analyses of serum have the potential to identify such probable markers. A discovery study is reported here using preoperative serum from 80 stomach cancer patients, 10 patients bearing benign stomach disease, and 20 matched controls. Glycomic analysis of the total and immunoaffinity depleted serum revealed statistically significant increases in the levels of sialyl Lewis X epitopes (SLe(X)) present on triantennary glycans accompanied by increased levels of core fucosylated agalactosyl biantennary glycans present on IgG (referred to as the IgG G0 glycoform) which are associated with increasing disease pathogenesis. Protein expression analysis using 2D-DiGE returned a number of differentially expressed protein candidates in the depleted serum, many of which were shown to carry triantennary SLe(X) during subsequent glycomic investigations. Biological pathway analysis of the experimental data returned complement activation and acute phase response signaling as the most significantly altered pathways in the stomach cancer patient serum. Upon the basis of these findings, it is suggested that increased expression of IgG G0 and complement activation are a host response to the presence of the stomach tumor while the increased expression of SLe(X) and acute phase response proteins is a result of pro-inflammatory cytokine signaling, including IL-6, during carcinogenesis. The approach presented herein provides an insight into the underlying mechanisms of disease and the resulting changes in the glycome and glycoproteome offer promise as potential markers for diagnosis and prognostic monitoring in stomach cancer.
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Affiliation(s)
- Jonathan Bones
- NIBRT Dublin-Oxford Glycobiology Laboratory, The National Institute for Bioprocessing Research and Training, University College Dublin, Belfield, Dublin 4, Ireland
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He C, Zheng S, Zhang J, Duan A, Zeng Y, Cui K. Clonal reproduction and natural variation of Populus canescens patches. TREE PHYSIOLOGY 2010; 30:1383-1390. [PMID: 21030405 DOI: 10.1093/treephys/tpq083] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
Trees growing in their natural habitat represent a valuable resource for elucidating mechanisms of adaptation to environmental constraints. Along the Erqis river, there are various Populus forests, which provide 'natural laboratories' for studying tree ecophysiological responses to their habitat. Reproduction strategies and natural variation of the 'mosaic' distributed Populus canescens patches were studied using a proteomic approach and nuclear microsatellite markers. Clonal reproduction was the primary reproduction strategy of these P. canescens patches. Forty-eight percent of the locations represented in one or two P. canescens patches were identified. In total, 83 different proteins were identified in 118 of 119 protein spots, most of them involved in metabolism. Distinct proteomes and post-translational modifications were found in different P. canescens patches. The differences in the proteomes originate both from the expression of different protein isoforms with the same function and from the differential expression of proteins with different functions, suggesting that different patches might have a functional basis for their adaptation to their environments. Our studies provide a good example of applying proteomics to measure natural variation between patches and will provide a basis for understanding how trees survive through their responses to natural conditions.
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Affiliation(s)
- Caiyun He
- Key Laboratory of Silviculture of the State Forestry Administration, Research Institute of Forestry, Chinese Academy of Forestry, Beijing 100091, People's Republic of China
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