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Ge QM, Hu QH, Liu JX, Min YL, Liang RB, Li B, Shi WQ, Lin Q, Yuan Q, Li QY, Shao Y. Cancer antigen 153: A risk factor for ocular metastases in patients with breast cancer. Exp Ther Med 2024; 28:421. [PMID: 39301252 PMCID: PMC11412098 DOI: 10.3892/etm.2024.12710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 12/19/2022] [Indexed: 09/22/2024] Open
Abstract
Ocular metastasis (OM) in breast cancer (BC) always predicts poor prognosis. The present study explored differences in tumor markers in patients with BC with and without OM, and attempted to determine risk factors for OM in patients with BC. This study involved 629 patients with BC. Patients' clinical features were tested using χ2 test, unpaired Student's t-test and Mann-Whitney U. These parameters were analyzed using binary logistic regression to obtain risk factors for OM. A receiver operating characteristic curve was then established to determine the diagnostic value for OM. There were no significant differences in age, sex, menopausal state, and pathological type between the two groups. Significantly more axillary lymph node metastases were observed in the OM group compared with the non-ocular metastases group. Cancer antigen 153 (CA153) was revealed to be a significant independent risk factor for OM in patients with BC. The cutoff CA153 value for diagnosis of OM was 43.00 u/ml, the sensitivity was 96.15% and the specificity was 96.02%. In conclusion, CA153 was demonstrated to be a risk factor for OM in patients with BC. High levels of CA153 were associated with OM in patients with BC.
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Affiliation(s)
- Qian-Min Ge
- Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Qiao-Hao Hu
- Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Jia-Xiang Liu
- Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - You-Lan Min
- Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Rong-Bin Liang
- Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Biao Li
- Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Wen-Qing Shi
- Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Qi Lin
- Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Qing Yuan
- Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Qiu-Yu Li
- Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Yi Shao
- Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
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Brown AR, Branthwaite HE, Farahbakhsh ZZ, Mukerjee S, Melugin PR, Song K, Noamany H, Siciliano CA. Structured tracking of alcohol reinforcement (STAR) for basic and translational alcohol research. Mol Psychiatry 2023; 28:1585-1598. [PMID: 36849824 PMCID: PMC10208967 DOI: 10.1038/s41380-023-01994-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 01/26/2023] [Accepted: 02/07/2023] [Indexed: 03/01/2023]
Abstract
There is inherent tension between methodologies developed to address basic research questions in model species and those intended for preclinical to clinical translation: basic investigations require flexibility of experimental design as hypotheses are rapidly tested and revised, whereas preclinical models emphasize standardized protocols and specific outcome measures. This dichotomy is particularly relevant in alcohol research, which spans a diverse range of basic sciences in addition to intensive efforts towards understanding the pathophysiology of alcohol use disorder (AUD). To advance these goals there is a great need for approaches that facilitate synergy across basic and translational areas of nonhuman alcohol research. In male and female mice, we establish a modular alcohol reinforcement paradigm: Structured Tracking of Alcohol Reinforcement (STAR). STAR provides a robust platform for quantitative assessment of AUD-relevant behavioral domains within a flexible framework that allows direct crosstalk between translational and mechanistically oriented studies. To achieve cross-study integration, despite disparate task parameters, a straightforward multivariate phenotyping analysis is used to classify subjects based on propensity for heightened alcohol consumption and insensitivity to punishment. Combining STAR with extant preclinical alcohol models, we delineate longitudinal phenotype dynamics and reveal putative neuro-biomarkers of heightened alcohol use vulnerability via neurochemical profiling of cortical and brainstem tissues. Together, STAR allows quantification of time-resolved biobehavioral processes essential for basic research questions simultaneous with longitudinal phenotyping of clinically relevant outcomes, thereby providing a framework to facilitate cohesion and translation in alcohol research.
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Affiliation(s)
- Alex R Brown
- Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, 37232, USA
| | - Hannah E Branthwaite
- Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, 37232, USA
| | - Zahra Z Farahbakhsh
- Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, 37232, USA
| | - Snigdha Mukerjee
- Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, 37232, USA
| | - Patrick R Melugin
- Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, 37232, USA
| | - Keaton Song
- Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, 37232, USA
| | - Habiba Noamany
- Department of Neurobiology, Harvard Medical School, Boston, MA, USA
| | - Cody A Siciliano
- Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, 37232, USA.
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Arip M, Tan LF, Jayaraj R, Abdullah M, Rajagopal M, Selvaraja M. Exploration of biomarkers for the diagnosis, treatment and prognosis of cervical cancer: a review. Discov Oncol 2022; 13:91. [PMID: 36152065 PMCID: PMC9509511 DOI: 10.1007/s12672-022-00551-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 06/16/2022] [Indexed: 12/19/2022] Open
Abstract
As the fourth most diagnosed cancer, cervical cancer (CC) is one of the major causes of cancer-related mortality affecting females globally, particularly when diagnosed at advanced stage. Discoveries of CC biomarkers pave the road to precision medicine for better patient outcomes. High throughput omics technologies, characterized by big data production further accelerate the process. To date, various CC biomarkers have been discovered through the advancement in technologies. Despite, very few have successfully translated into clinical practice due to the paucity of validation through large scale clinical studies. While vast amounts of data are generated by the omics technologies, challenges arise in identifying the clinically relevant data for translational research as analyses of single-level omics approaches rarely provide causal relations. Integrative multi-omics approaches across different levels of cellular function enable better comprehension of the fundamental biology of CC by highlighting the interrelationships of the involved biomolecules and their function, aiding in identification of novel integrated biomarker profile for precision medicine. Establishment of a worldwide Early Detection Research Network (EDRN) system helps accelerating the pace of biomarker translation. To fill the research gap, we review the recent research progress on CC biomarker development from the application of high throughput omics technologies with sections covering genomics, transcriptomics, proteomics, and metabolomics.
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Affiliation(s)
- Masita Arip
- Allergy & Immunology Research Centre, Institute for Medical Research, National Institute of Health, Setia Alam, 40170 Shah Alam, Selangor, Malaysia
| | - Lee Fang Tan
- Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia.
| | - Rama Jayaraj
- Charles Darwin University, Darwin, NT, 0909, Australia
| | - Maha Abdullah
- Immunology Unit, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Jalan Serdang, 43400, Serdang, Selangor, Malaysia
| | - Mogana Rajagopal
- Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia.
| | - Malarvili Selvaraja
- Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia.
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Wuputra K, Ku CC, Pan JB, Liu CJ, Liu YC, Saito S, Kato K, Lin YC, Kuo KK, Chan TF, Chong IW, Lin CS, Wu DC, Yokoyama KK. Stem Cell Biomarkers and Tumorigenesis in Gastric Cancer. J Pers Med 2022; 12:jpm12060929. [PMID: 35743714 PMCID: PMC9224738 DOI: 10.3390/jpm12060929] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 05/25/2022] [Accepted: 05/31/2022] [Indexed: 02/01/2023] Open
Abstract
Stomach cancer has a high mortality, which is partially caused by an absence of suitable biomarkers to allow detection of the initiation stages of cancer progression. Thus, identification of critical biomarkers associated with gastric cancer (GC) is required to advance its clinical diagnoses and treatment. Recent studies using tracing models for lineage analysis of GC stem cells indicate that the cell fate decision of the gastric stem cells might be an important issue for stem cell plasticity. They include leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5+), Cholecystokinin receptor 2 (Cckr2+), and axis inhibition protein 2 (Axin2+) as the stem cell markers in the antrum, Trefoil Factor 2 (TFF2+), Mist1+ stem cells, and Troy+ chief cells in the corpus. By contrast, Estrogen receptor 1 (eR1), Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1), SRY (sex determining region Y)-box 2 (Sox2), and B lymphoma Mo-MLV insertion region 1 homolog (Bmi1) are rich in both the antrum and corpus regions. These markers might help to identify the cell-lineage identity and analyze the plasticity of each stem cell population. Thus, identification of marker genes for the development of GC and its environment is critical for the clinical application of cancer stem cells in the prevention of stomach cancers.
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Affiliation(s)
- Kenly Wuputra
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (K.W.); (C.-C.K.); (J.-B.P.); (C.-S.L.)
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-J.L.); (K.-K.K.); (D.-C.W.)
- Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan;
| | - Chia-Chen Ku
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (K.W.); (C.-C.K.); (J.-B.P.); (C.-S.L.)
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-J.L.); (K.-K.K.); (D.-C.W.)
- Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan;
| | - Jia-Bin Pan
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (K.W.); (C.-C.K.); (J.-B.P.); (C.-S.L.)
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-J.L.); (K.-K.K.); (D.-C.W.)
- Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan;
| | - Chung-Jung Liu
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-J.L.); (K.-K.K.); (D.-C.W.)
- Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan;
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
- Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Yi-Chang Liu
- Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan;
| | - Shigeo Saito
- Saito Laboratory of Cell Technology, Yaita 329-2192, Japan;
- Horus Co., Ltd., Nakano, Tokyo 164-0001, Japan
| | - Kohsuke Kato
- Department of Infection Biology, Graduate School of Comprehensive Human Sciences, The University of Tsukuba, Tsukuba 305-8577, Japan;
| | - Ying-Chu Lin
- School of Dentistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | - Kung-Kai Kuo
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-J.L.); (K.-K.K.); (D.-C.W.)
- Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan;
- Division of General & Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
| | - Te-Fu Chan
- Department of Obstetrics and Genecology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan;
| | - Inn-Wen Chong
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan;
| | - Chang-Shen Lin
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (K.W.); (C.-C.K.); (J.-B.P.); (C.-S.L.)
| | - Deng-Chyang Wu
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-J.L.); (K.-K.K.); (D.-C.W.)
- Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan;
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
- Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Obstetrics and Genecology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan;
| | - Kazunari K. Yokoyama
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (K.W.); (C.-C.K.); (J.-B.P.); (C.-S.L.)
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-J.L.); (K.-K.K.); (D.-C.W.)
- Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan;
- Correspondence: ; Tel.: +886-7312-1101 (ext. 2729); Fax: +886-7313-3849
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Mousavi SM, Hashemi SA, Kalashgrani MY, Gholami A, Omidifar N, Babapoor A, Vijayakameswara Rao N, Chiang WH. Recent Advances in Plasma-Engineered Polymers for Biomarker-Based Viral Detection and Highly Multiplexed Analysis. BIOSENSORS 2022; 12:286. [PMID: 35624587 PMCID: PMC9138656 DOI: 10.3390/bios12050286] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 04/22/2022] [Accepted: 04/27/2022] [Indexed: 05/07/2023]
Abstract
Infectious diseases remain a pervasive threat to global and public health, especially in many countries and rural urban areas. The main causes of such severe diseases are the lack of appropriate analytical methods and subsequent treatment strategies due to limited access to centralized and equipped medical centers for detection. Rapid and accurate diagnosis in biomedicine and healthcare is essential for the effective treatment of pathogenic viruses as well as early detection. Plasma-engineered polymers are used worldwide for viral infections in conjunction with molecular detection of biomarkers. Plasma-engineered polymers for biomarker-based viral detection are generally inexpensive and offer great potential. For biomarker-based virus detection, plasma-based polymers appear to be potential biological probes and have been used directly with physiological components to perform highly multiplexed analyses simultaneously. The simultaneous measurement of multiple clinical parameters from the same sample volume is possible using highly multiplexed analysis to detect human viral infections, thereby reducing the time and cost required to collect each data point. This article reviews recent studies on the efficacy of plasma-engineered polymers as a detection method against human pandemic viruses. In this review study, we examine polymer biomarkers, plasma-engineered polymers, highly multiplexed analyses for viral infections, and recent applications of polymer-based biomarkers for virus detection. Finally, we provide an outlook on recent advances in the field of plasma-engineered polymers for biomarker-based virus detection and highly multiplexed analysis.
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Affiliation(s)
- Seyyed Mojtaba Mousavi
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei City 106335, Taiwan;
| | - Seyyed Alireza Hashemi
- Nanomaterials and Polymer Nanocomposites Laboratory, School of Engineering, University of British Columbia, Kelowna, BC V1V 1V7, Canada;
| | - Masoomeh Yari Kalashgrani
- Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran; (M.Y.K.); (A.G.)
| | - Ahmad Gholami
- Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran; (M.Y.K.); (A.G.)
| | - Navid Omidifar
- Department of Pathology, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran;
| | - Aziz Babapoor
- Department of Chemical Engineering, University of Mohaghegh Ardabil, Ardabil 56199-11367, Iran;
| | - Neralla Vijayakameswara Rao
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei City 106335, Taiwan;
| | - Wei-Hung Chiang
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei City 106335, Taiwan;
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6
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Hong X, Liu F. Editorial: Molecular Biomarkers for Gastric Cancer. Front Oncol 2022; 12:850373. [PMID: 35186772 PMCID: PMC8850303 DOI: 10.3389/fonc.2022.850373] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 01/17/2022] [Indexed: 01/04/2023] Open
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Blomberg K, Hansen TF, Brasen CL, Madsen JB, Jensen LH, Thomsen CB. The Soluble Urokinase-Type Plasminogen Activator Receptor as a Biomarker for Survival and Early Treatment Effect in Metastatic Colorectal Cancer. Cancers (Basel) 2021; 13:5100. [PMID: 34680247 PMCID: PMC8534079 DOI: 10.3390/cancers13205100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 10/07/2021] [Accepted: 10/08/2021] [Indexed: 12/17/2022] Open
Abstract
The soluble urokinase-type plasminogen activator receptor (suPAR) is prognostic for overall survival (OS) in colorectal cancer (CRC). Our study explored the association between baseline suPAR and OS and progression-free survival (PFS) in metastatic CRC (mCRC). It is also the first study to explore the association between the initial change in suPAR level and OS, PFS and the first CT response evaluation. The study included 132 patients with mCRC treated with chemotherapy (FOLFIRI) with or without an EGFR-inhibitor. Blood samples were drawn before the first treatment cycle and in between the first and second treatment cycle. suPAR levels were determined using an ELISA assay. Using the Kaplan-Meyer method, we demonstrated a significantly shorter OS for patients with suPAR levels above the median (HR = 1.79, 95%CI = 1.10-2.92, p = 0.01). We also showed association between plasma suPAR level, gender and performance status (PS). However, we could not show any association with PFS, and analysis on the change in suPAR level provided no significant results. The results showing association between baseline suPAR and OS are in line with previous findings.
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Affiliation(s)
- Kristian Blomberg
- Department of Health Science, University of Southern Denmark, 5000 Odense, Denmark;
- Danish Colorectal Cancer Center South, Department of Oncology, University Hospital of Southern Denmark, 7100 Vejle, Denmark; (T.F.H.); (L.H.J.)
| | - Torben F. Hansen
- Danish Colorectal Cancer Center South, Department of Oncology, University Hospital of Southern Denmark, 7100 Vejle, Denmark; (T.F.H.); (L.H.J.)
- Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark;
| | - Claus L. Brasen
- Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark;
- Department of Biochemistry and Immunology, Lillebaelt Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark;
| | - Jeppe B. Madsen
- Department of Biochemistry and Immunology, Lillebaelt Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark;
| | - Lars H. Jensen
- Danish Colorectal Cancer Center South, Department of Oncology, University Hospital of Southern Denmark, 7100 Vejle, Denmark; (T.F.H.); (L.H.J.)
- Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark;
- Open Patient Data Explorative Network, The Clinical Institute, Odense University Hospital, 5000 Odense, Denmark
| | - Caroline B. Thomsen
- Danish Colorectal Cancer Center South, Department of Oncology, University Hospital of Southern Denmark, 7100 Vejle, Denmark; (T.F.H.); (L.H.J.)
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Lakpour N, Saliminejad K, Ghods R, Reza Sadeghi M, Pilatz A, Khosravi F, Madjd Z. Potential biomarkers for testicular germ cell tumour: Risk assessment, diagnostic, prognostic and monitoring of recurrence. Andrologia 2021; 53:e13998. [PMID: 33534171 DOI: 10.1111/and.13998] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 01/01/2021] [Accepted: 01/12/2021] [Indexed: 12/17/2022] Open
Abstract
Testicular germ cell tumour (TGCT) is considered a relatively rare malignancy usually occurring in young men between 15 and 35 years of age, and both genetic and environmental factors contribute to its development. The majority of patients are diagnosed in an early-stage of TGCTs with an elevated 5-year survival rate after therapy. However, approximately 25% of patients show an incomplete response to chemotherapy or tumours relapse. The current therapies are accompanied by several adverse effects, including infertility. Aside from classical serum biomarker, many studies reported novel biomarkers for TGCTs, but without proper validation. Cancer cells share many similarities with embryonic stem cells (ESCs), and since ESC genes are not transcribed in most adult tissues, they could be considered ideal candidate targets for cancer-specific diagnosis and treatment. Added to this, several microRNAs (miRNA) including miRNA-371-3p can be further investigated as a molecular biomarker for diagnosis and monitoring of TGCTs. In this review, we will illustrate the findings of recent investigations in novel TGCTs biomarkers applicable for risk assessment, screening, diagnosis, prognosis, prediction and monitoring of the relapse.
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Affiliation(s)
- Niknam Lakpour
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran.,Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| | - Kioomars Saliminejad
- Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| | - Roya Ghods
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran.,Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Sadeghi
- Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| | - Adrian Pilatz
- Department of Urology, Pediatric Urology and Andrology, Justus Liebig University, Giessen, Germany
| | - Farhad Khosravi
- Department of Physiology, Faculty of Medicine, Justus Liebig University, Giessen, Germany
| | - Zahra Madjd
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran.,Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
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Srivastava S, Wagner PD. The Early Detection Research Network: A National Infrastructure to Support the Discovery, Development, and Validation of Cancer Biomarkers. Cancer Epidemiol Biomarkers Prev 2020; 29:2401-2410. [PMID: 32357955 PMCID: PMC11106613 DOI: 10.1158/1055-9965.epi-20-0237] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 03/30/2020] [Accepted: 04/08/2020] [Indexed: 11/16/2022] Open
Abstract
In 2000, the NCI (Rockville, MD) established the Early Detection Research Network (EDRN) to identify, develop, and validate biomarkers to improve the detection of early-stage cancers and risk assessment. This consortium of more than 300 investigators at academic institutions and in the private sector is working collaboratively to bring biomarkers and imaging methods to clinical fruition. Although significant roadblocks have hindered the field of biomarker discovery and validation, the EDRN has helped overcome many of them by setting well-defined strategies and milestones focused on solving defined unmet clinical needs. The EDRN has implemented measures to improve biomarker discovery and validation, such as data sharing, use of common data elements, generating multidisciplinary and multi-institutional collaborations within a cohesive and productive team environment, and putting emphasis on quality control and data replication for all candidate biomarkers for reaching a "go" or "no go" decision. A measure of the success of the EDRN is the number of biomarkers tests or devices approved by the FDA to which EDRN investigators have made significant contributions and the number of biomarkers tests developed by EDRN investigators that are available in Clinical Laboratory Improvement Amendments laboratories.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."
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Affiliation(s)
- Sudhir Srivastava
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - Paul D Wagner
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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Value of Serum NEUROG1 Methylation for the Detection of Advanced Adenomas and Colorectal Cancer. Diagnostics (Basel) 2020; 10:diagnostics10070437. [PMID: 32605302 PMCID: PMC7399835 DOI: 10.3390/diagnostics10070437] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 06/23/2020] [Accepted: 06/26/2020] [Indexed: 02/06/2023] Open
Abstract
Aberrant DNA methylation detected in liquid biopsies is a promising approach for colorectal cancer (CRC) detection, including premalignant advanced adenomas (AA). We evaluated the diagnostic capability of serum NEUROG1 methylation for the detection of AA and CRC. A CpG island in NEUROG1 promoter was assessed by bisulfite pyrosequencing in a case-control cohort to select optimal CpGs. Selected sites were evaluated through a nested methylation-specific qPCR custom assay in a screening cohort of 504 asymptomatic family-risk individuals. Individuals with no colorectal findings and benign pathologies showed low serum NEUROG1 methylation, similar to non-advanced adenomas. Contrarily, individuals bearing AA or CRC (advanced neoplasia—AN), exhibited increased NEUROG1 methylation. Using >1.3518% as NEUROG1 cut-off (90.60% specificity), 33.33% of AN and 32.08% of AA were identified, detecting 50% CRC cases. Nonetheless, the combination of NEUROG1 with fecal immunochemical test (FIT), together with age and gender through a multivariate logistic regression resulted in an AUC = 0.810 for AN, and 0.796 for AA, detecting all cancer cases and 35–47% AA (specificity 98–95%). The combination of NEUROG1 methylation with FIT, age and gender demonstrated a convenient performance for the detection of CRC and AA, providing a valuable tool for CRC screening programs in asymptomatic individuals.
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11
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Assad DX, Mascarenhas ECP, de Lima CL, de Toledo IP, Chardin H, Combes A, Acevedo AC, Guerra ENS. Salivary metabolites to detect patients with cancer: a systematic review. Int J Clin Oncol 2020; 25:1016-1036. [PMID: 32221803 DOI: 10.1007/s10147-020-01660-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 03/10/2020] [Indexed: 12/16/2022]
Abstract
Novel adjunctive screening aids are needed to reduce the morbidity and mortality related to cancer, and every effort should be made for early diagnosis. This systematic review aimed to evaluate salivary metabolites and their diagnostic value in patients with cancer.The systematic review was performed in two phases and included studies that focused on the diagnostic value of salivary metabolites in humans with solid malignant neoplasms. Five electronic databases were searched, and the risk of bias in individual studies was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2). All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Of the 1151 studies retrieved, 25 were included; 13 studies used targeted and 12 untargeted metabolomics approaches. Most studies included patients with breast and oral cancer. Except for one, all studies had case-control designs, and none fulfilled all quality assessments. Overall, 140 salivary metabolites were described. The most frequently reported metabolites were alanine, valine, and leucine. Among the 11 studies that reported diagnostic test accuracy (DTA) values, proline, threonine, and histidine in combination and monoacylglycerol alone demonstrated the highest DTA for breast cancer. Combined choline, betaine, pipecolinic acid, and L-carnitine showed better discriminatory performance for early oral cancer.This systematic review highlights the current evidence on salivary metabolites that may be used as a future strategy to diagnose cancer. Further studies including larger sample sizes with confirmation of the results by untargeted analysis are warranted.
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Affiliation(s)
- Daniele Xavier Assad
- Laboratory of Oral Histopathology, Health Sciences Faculty, University of Brasília, Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil.,Medical Oncology Department, Hospital Sírio-Libanês, SGAS 613 Conj. E Bl. B, Brasília, DF, 70200-730, Brazil
| | - Elisa Cançado Porto Mascarenhas
- Laboratory of Oral Histopathology, Health Sciences Faculty, University of Brasília, Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil.,Medical Oncology Department, Cettro-Centro de Câncer de Brasília, SMH/N Quadra 02, 12° Andar, Brasilia, DF, 70710-904, Brazil
| | - Caroline Lourenço de Lima
- Laboratory of Oral Histopathology, Health Sciences Faculty, University of Brasília, Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil
| | - Isabela Porto de Toledo
- Laboratory of Oral Histopathology, Health Sciences Faculty, University of Brasília, Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil
| | - Hélène Chardin
- Department of Analytical, Bioanalytical Sciences and Miniaturization (LSABM), ESPCI Paris, UMR CBI 8231, PSL Research University, 10 Rue Vauquelin, Paris, 75005, France.,Faculté de Chirurgie Dentaire, Université de Paris, 1 rue M. Arnoux, 92120, Montrouge, France
| | - Audrey Combes
- Department of Analytical, Bioanalytical Sciences and Miniaturization (LSABM), ESPCI Paris, UMR CBI 8231, PSL Research University, 10 Rue Vauquelin, Paris, 75005, France
| | - Ana Carolina Acevedo
- Laboratory of Oral Histopathology, Health Sciences Faculty, University of Brasília, Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil
| | - Eliete Neves Silva Guerra
- Laboratory of Oral Histopathology, Health Sciences Faculty, University of Brasília, Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, Brazil.
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12
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Li J, Li X. Comprehensive analysis of prognosis-related methylated sites in breast carcinoma. Mol Genet Genomic Med 2020; 8:e1161. [PMID: 32037691 PMCID: PMC7196449 DOI: 10.1002/mgg3.1161] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 11/20/2019] [Accepted: 01/23/2020] [Indexed: 12/26/2022] Open
Abstract
Background Breast carcinoma has become a nonnegligible public health problem in China with its increasing incidence and mortality in woman. As a early event regulating tumorigenesis and development, DNA methylation became one of the focuses of current carcinoma researches on potential diagnostic and therapeutic targets. Methods In this study, we comprehensively analyzed the gene expression data and DNA methylation data of breast carcinoma and adjacent normal tissues samples in the Gene Expression Omnibus database. Influences of tumor stage, adjuvant therapy, hormone therapy, and chemotherapy on CpG methylation level were explored by linear regression analysis. Correlations between methylation and gene expression levels were determined by spearman rank correlation analysis. Log‐rank test was applied for determining significance of associations between CpG sites methylation level and breast cancer patients' Kaplan–Meier survival. Results A total of 229 CpG sites were found to be significantly associated with tumor stage or treatment, and eight of which were potential markers that affect the survival of breast carcinoma and negatively correlated with their genes' expression levels. Conclusions We reported eight CpG sites as potential breast cancer prognosis signatures through comprehensively analyzed gene expression and DNA methylation datasets, and excluding influences of tumor stage and treatment. This should be helpful for breast cancer early diagnosis and treatment.
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Affiliation(s)
- Jia Li
- Department of Breast Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, P.R. China
| | - Xinzheng Li
- Department of Breast Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, P.R. China
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13
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Zayas B, Lebron V, Vélez C, Cox O. Novel NBQ-48 as marker of hypoxic cells in 2D and 3D colon cancer cells. JOURNAL OF CANCER PREVENTION & CURRENT RESEARCH 2020; 11:13-18. [PMID: 34765722 PMCID: PMC8580369 DOI: 10.15406/jcpcr.2020.11.00417] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
This study presents the applicability of a novel nitro-substituted heterocyclic compound NBQ48, member of the family of compounds identified as 3 nitrobenzazolo[3, 2-a] quinolinium chloride salts (NBQS) as a screening tool to identify hypoxic tumor cells. The applicability was tested on COLO 205 colon cancer cells 2D and 3D cultures treated with NBQ48 to assess the formation of a bio-reduction fluorescent metabolite under hypoxic conditions in contrast, to those under aerobic environment. Hypoxic environment was created applying a controlled hypoxic gas chamber. Prior to testing the applicability of NBQ48 as a hypoxic fluorescent marker, cytotoxic studies where performed to identify a low-toxicity dose at 24 hours under aerobic and hypoxic environments that would allow the bio-reduction process with little toxicity. The differences in fluorescence emission after treatment was measured by fluorometer and fluorescence microscopy. Results indicated that cell treatments up to 24 hours with NBQ48 under aerobic environment did not reach an IC50 dose in COLO205 cells, however under hypoxic environment the IC50 reached at 100μM. The significant fluorescence increment after 24 and 48 hrs in 2D and 3D cultures treated with NBQ48 (75uM) at hypoxic in contrast to aerobic environments clearly demonstrated the need of a low oxygen content for the bio-reduction of the parent NBQ48. This study confirms the applicability of NBQ48 as markers for hypoxia in metabolically active 2D and 3D cultures. This hydrophilic hypoxic marker could additionally aid researchers in testing hypoxia activated pro-drugs for therapeutic applications in cancer as well as on other diseases where cellular hypoxia is a significant risk factor.
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Affiliation(s)
- Beatriz Zayas
- School of Science, Technology and Environment, Ana G. Mendez University (UAGM), USA
| | - Vivian Lebron
- School of Science, Technology and Environment, Ana G. Mendez University (UAGM), USA
| | - Christian Vélez
- School of Science, Technology and Environment, Ana G. Mendez University (UAGM), USA
| | - Osvaldo Cox
- School of Science, Technology and Environment, Ana G. Mendez University (UAGM), USA
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14
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Lovergne L, Lovergne J, Bouzy P, Untereiner V, Offroy M, Garnotel R, Thiéfin G, Baker MJ, Sockalingum GD. Investigating pre-analytical requirements for serum and plasma based infrared spectro-diagnostic. JOURNAL OF BIOPHOTONICS 2019; 12:e201900177. [PMID: 31276294 DOI: 10.1002/jbio.201900177] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Revised: 07/02/2019] [Accepted: 07/04/2019] [Indexed: 06/09/2023]
Abstract
Infrared spectroscopy is a rapid, easy-to-operate, label-free and therefore cost-effective technique. Many studies performed on biofluids (eg, serum, plasma, urine, sputum, bile and cerebrospinal fluid) have demonstrated its promising application as a clinical diagnostic tool. Given all these characteristics, infrared spectroscopy appears to be an ideal candidate to be implemented into the clinics. However, before considering its translation, a clear effort is needed to standardise protocols for biofluid spectroscopic analysis. To reach this goal, careful investigations to identify and track errors that can occur during the pre-analytical phase is a crucial step. Here, we report for the first time, results of investigations into pre-analytical factors that can affect the quality of the spectral data acquired on serum and plasma, such as the impact of long-term freezing time storage of samples as well as the month-to-month reproducibility of the spectroscopic analysis. The spectral data discrimination has revealed to be majorly impacted by a residual water content variation in serum and plasma dried samples.
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Affiliation(s)
- Lila Lovergne
- Université de Reims Champagne-Ardenne, BioSpecT EA7506, UFR de Pharmacie, Reims, France
- WESTChem, Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, Glasgow, UK
| | - Jean Lovergne
- WESTChem, Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, Glasgow, UK
| | - Pascaline Bouzy
- Université de Reims Champagne-Ardenne, BioSpecT EA7506, UFR de Pharmacie, Reims, France
| | - Valérie Untereiner
- Université de Reims Champagne-Ardenne, BioSpecT EA7506, UFR de Pharmacie, Reims, France
- Université de Reims Champagne-Ardenne, Plateforme en Imagerie Cellulaire et Tissulaire (PICT), Reims, France
| | - Marc Offroy
- Université de Reims Champagne-Ardenne, BioSpecT EA7506, UFR de Pharmacie, Reims, France
| | - Roselyne Garnotel
- Université de Reims Champagne-Ardenne, BioSpecT EA7506, UFR de Pharmacie, Reims, France
- CHU de Reims, Hôpital Maison Blanche, Laboratoire de Biochimie-Pharmacologie-Toxicologie, Reims, France
| | - Gérard Thiéfin
- Université de Reims Champagne-Ardenne, BioSpecT EA7506, UFR de Pharmacie, Reims, France
- CHU de Reims, Hôpital Robert Debré, Service d'hépato- Gastroentérologie, Reims, France
| | - Matthew J Baker
- WESTChem, Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, Glasgow, UK
| | - Ganesh D Sockalingum
- Université de Reims Champagne-Ardenne, BioSpecT EA7506, UFR de Pharmacie, Reims, France
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15
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Tan LP, Tan GW, Sivanesan VM, Goh SL, Ng XJ, Lim CS, Kim WR, Mohidin TBBM, Mohd Dali NS, Ong SH, Wong CY, Sawali H, Yap YY, Hassan F, Pua KC, Koay CE, Ng CC, Khoo ASB. Systematic comparison of plasma EBV DNA, anti-EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma. Int J Cancer 2019; 146:2336-2347. [PMID: 31469434 PMCID: PMC7065012 DOI: 10.1002/ijc.32656] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 07/17/2019] [Accepted: 08/15/2019] [Indexed: 12/31/2022]
Abstract
Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein–Barr virus (EBV)‐associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost‐effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI‐W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI‐W 121 bp and ebv‐miR‐BART7‐3p were validated. Hsa‐miR‐29a‐3p and hsa‐miR‐103a‐3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI‐W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling. What's new? Plasma Epstein–Barr virus (EBV) DNA is an established nasopharyngeal carcinoma (NPC) biomarker, but not all cases are associated with EBV and its sensitivity for stage I NPC remains controversial. Meanwhile, most newly‐reported NPC biomarkers have neither been externally validated nor compared to established biomarkers. This study systematically evaluates six established and four new biomarkers in NPC cases, population controls, and hospital controls. The findings provide evidence to policymakers for improvement in NPC screening and monitoring strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity/specificity, and testing multiple biomarkers on single specimens to avoid the logistic problems of resampling.
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Affiliation(s)
- Lu Ping Tan
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Ministry of Health Malaysia, Kuala Lumpur, Malaysia.,Department of Medical Sciences, School of Healthcare and Medical Sciences, Sunway University, Selangor, Malaysia
| | - Geok Wee Tan
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Ministry of Health Malaysia, Kuala Lumpur, Malaysia.,Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Vijaya Mohan Sivanesan
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Ministry of Health Malaysia, Kuala Lumpur, Malaysia
| | - Siang Ling Goh
- Faculty of Science, University of Malaya, Institute of Biological Sciences, Kuala Lumpur, Malaysia
| | - Xun Jin Ng
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Ministry of Health Malaysia, Kuala Lumpur, Malaysia
| | - Chun Shen Lim
- Faculty of Science, University of Malaya, Institute of Biological Sciences, Kuala Lumpur, Malaysia.,Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
| | - Wee Ric Kim
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Ministry of Health Malaysia, Kuala Lumpur, Malaysia
| | | | - Nor Soleha Mohd Dali
- Haematology Unit, Cancer Research Centre, Institute for Medical Research, Ministry of Health Malaysia, Kuala Lumpur, Malaysia
| | - Siew Hoon Ong
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Ministry of Health Malaysia, Kuala Lumpur, Malaysia
| | - Chun Ying Wong
- Department of Otorhinolaryngology, Sarawak General Hospital, Ministry of Health Malaysia, Jalan Hospital, Kuching, Sarawak, Malaysia
| | - Halimuddin Sawali
- Department of Otorhinolaryngology, Queen Elizabeth Hospital, Ministry of Health Malaysia, Kota Kinabalu, Sabah, Malaysia
| | - Yoke Yeow Yap
- Department of Otorhinolaryngology, Kuala Lumpur Hospital, Ministry of Health Malaysia, Kuala Lumpur, Malaysia.,Department of Surgery, Clinical Campus Faculty of Medicine and Health Sciences, University Putra Malaysia at Kuala Lumpur Hospital, Ministry of Health Malaysia, Kuala Lumpur, Malaysia
| | - Faridah Hassan
- Department of Otorhinolaryngology, Selayang Hospital, Ministry of Health Malaysia, Batu Caves, Selangor, Malaysia
| | - Kin Choo Pua
- Department of Otorhinolaryngology, Pulau Pinang Hospital, Ministry of Health Malaysia, Georgetown, Pulau Pinang, Malaysia
| | - Cheng Eng Koay
- Gleneagles Kuala Lumpur Hospital, Kuala Lumpur, Malaysia.,Sunway Medical Centre, Bandar Sunway, Selangor, Malaysia
| | - Ching Ching Ng
- Faculty of Science, University of Malaya, Institute of Biological Sciences, Kuala Lumpur, Malaysia
| | - Alan Soo-Beng Khoo
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Ministry of Health Malaysia, Kuala Lumpur, Malaysia
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16
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Cruz A, Peng WK. Perspective: Cellular and Molecular Profiling Technologies in Personalized Oncology. J Pers Med 2019; 9:E44. [PMID: 31547284 PMCID: PMC6789676 DOI: 10.3390/jpm9030044] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 08/28/2019] [Accepted: 09/04/2019] [Indexed: 02/08/2023] Open
Abstract
Cancer is a leading cause of death worldwide and therefore one of the most important public health concerns. In this contribution, we discuss recent key enabling technological innovations (and their challenges), including biomarker-based technologies, that potentially allow for decentralization (e.g., self-monitoring) with the increasing availability of point-of-care technologies in the near future. These technological innovations are moving the field one step closer toward personalized oncology.
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Affiliation(s)
- Andrea Cruz
- International Iberian Nanotechnology Laboratory, 4715-330 Braga, Portugal.
| | - Weng Kung Peng
- International Iberian Nanotechnology Laboratory, 4715-330 Braga, Portugal.
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17
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Nakamura S, Kanda M, Kodera Y. Incorporating molecular biomarkers into clinical practice for gastric cancer. Expert Rev Anticancer Ther 2019; 19:757-771. [PMID: 31437076 DOI: 10.1080/14737140.2019.1659136] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Introduction: Gastric cancer is one of the most common causes of cancer-related mortality worldwide. To improve clinical outcomes, it is critical to develop appropriate approaches to diagnosis and treatment. Biomarkers have numerous potential clinical applications, including screening, assessing risk, determining prognosis, monitoring recurrence, and predicting response to treatment. Furthermore, biomarkers may contribute to the development of effective therapies. Areas covered: Here we review recent progress in exploiting GC-specific biomarkers such as protein-coding genes, microRNAs, long noncoding RNAs, and methylated gene promoters. Expert opinion: The development of biomarkers for diagnosing and monitoring gastric cancer and for individualizing therapeutic targets shows great promise for improving gastric cancer management.
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Affiliation(s)
- Shunsuke Nakamura
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine , Nagoya , Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine , Nagoya , Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine , Nagoya , Japan
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18
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Abstract
INTRODUCTION Cancer is often diagnosed at late stages when the chance of cure is relatively low and although research initiatives in oncology discover many potential cancer biomarkers, few transition to clinical applications. This review addresses the current landscape of cancer biomarker discovery and translation with a focus on proteomics and beyond. Areas covered: The review examines proteomic and genomic techniques for cancer biomarker detection and outlines advantages and challenges of integrating multiple omics approaches to achieve optimal sensitivity and address tumor heterogeneity. This discussion is based on a systematic literature review and direct participation in translational studies. Expert commentary: Identifying aggressive cancers early on requires improved sensitivity and implementation of biomarkers representative of tumor heterogeneity. During the last decade of genomic and proteomic research, significant advancements have been made in next generation sequencing and mass spectrometry techniques. This in turn has led to a dramatic increase in identification of potential genomic and proteomic cancer biomarkers. However, limited successes have been shown with translation of these discoveries into clinical practice. We believe that the integration of these omics approaches is the most promising molecular tool for comprehensive cancer evaluation, early detection and transition to Precision Medicine in oncology.
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Affiliation(s)
- Ventzislava A Hristova
- a Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA
| | - Daniel W Chan
- a Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA
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19
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Anastasi E, Gigli S, Ballesio L, Angeloni A, Manganaro L. The Complementary Role of Imaging and Tumor Biomarkers
in Gynecological Cancers: An Update of the Literature. Asian Pac J Cancer Prev 2018; 19:309-317. [PMID: 29479951 PMCID: PMC5980913 DOI: 10.22034/apjcp.2018.19.2.309] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Gynecological tumors, including endometrial, cervical and ovarian cancer, have increased in incidence over time. The widespread introduction of screening programs and advances in diagnostic imaging methods has lead to a progressive increase in gynecological cancer detection. Accurate diagnosis and proper monitoring of disease remain the primary target for a successful treatment. In the last years, knowledge about cancer biomarkers has considerably increased providing great opportunities for improving cancer detection and treatment. In addition, in the last few years there has been an important development of imaging techniques. Nowadays, a multimodal approach including the evaluation of serum tumor biomarkers combined with imaging techniques, seems to be the best strategy for assessing tumor presence, spread, recurrence, and/or the response to treatment in female cancer patients In this review we provide an overview of the application of biomarkers combined with novel imaging methods and highlight their roles in female cancer diagnosis and follow-up.
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Affiliation(s)
- Emanuela Anastasi
- Department of Molecular Medicine, Sapienza University, Viale Regina Elena 324, 00161 Roma, Italy.
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20
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Review: in vivo optical spectral tissue sensing-how to go from research to routine clinical application? Lasers Med Sci 2016; 32:711-719. [PMID: 27909918 DOI: 10.1007/s10103-016-2119-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Accepted: 11/22/2016] [Indexed: 10/20/2022]
Abstract
Innovations in optical spectroscopy have helped the technology reach a point where performance previously seen only in laboratory settings can be translated and tested in real-world applications. In the field of oncology, spectral tissue sensing (STS) by means of optical spectroscopy is considered to have major potential for improving diagnostics and optimizing treatment outcome. The concept has been investigated for more than two decades and yet spectral tissue sensing is not commonly employed in routine medical practice. It is therefore important to understand what is needed to translate technological advances and insights generated through basic scientific research in this field into clinical practice. The aim of the discussion presented here is not to provide a comprehensive review of all work published over the last decades but rather to highlight some of the challenges found in literature and encountered by our group in the quest to translate optical technologies into useful clinical tools. Furthermore, an outlook is proposed on how translational researchers could proceed to eventually have STS incorporated in the process of clinical decision-making.
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21
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Fleisher B, Clarke C, Ait-Oudhia S. Current advances in biomarkers for targeted therapy in triple-negative breast cancer. BREAST CANCER (DOVE MEDICAL PRESS) 2016; 8:183-197. [PMID: 27785100 PMCID: PMC5063595 DOI: 10.2147/bctt.s114659] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Triple-negative breast cancer (TNBC) is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials.gov. The selected candidate biomarkers were classified as surrogate, prognostic, predictive, or pharmacodynamic (PD) and organized by location in the blood, on the cell surface, in the cytoplasm, or in the nucleus. Blood biomarkers include vascular endothelial growth factor/vascular endothelial growth factor receptor and interleukin-8 (IL-8); cell surface biomarkers include EGFR, insulin-like growth factor binding protein, c-Kit, c-Met, and PD-L1; cytoplasm biomarkers include PIK3CA, pAKT/S6/p4E-BP1, PTEN, ALDH1, and the PIK3CA/AKT/mTOR-related metabolites; and nucleus biomarkers include BRCA1, the gluco-corticoid receptor, TP53, and Ki67. Candidate biomarkers were further organized into a "cellular protein network" that demonstrates potential connectivity. This review provides an inventory and reference point for promising biomarkers for breakthrough targeted therapies in TNBC.
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Affiliation(s)
- Brett Fleisher
- Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL
| | - Charlotte Clarke
- Department of Translational Research, UT MD Anderson Cancer Center, Houston, TX, USA
| | - Sihem Ait-Oudhia
- Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL
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22
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Evaluation of serum nucleoside diphosphate kinase A for the detection of colorectal cancer. Sci Rep 2016; 6:26703. [PMID: 27222072 PMCID: PMC4879623 DOI: 10.1038/srep26703] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 05/09/2016] [Indexed: 01/27/2023] Open
Abstract
We previously described the over-expression of nucleoside diphosphate kinase A (NDKA) in tumours and serum from colorectal cancer (CRC) patients, suggesting its use as biomarker. In this study we evaluated the diagnostic accuracy of serum NDKA to detect advanced neoplasia (CRC or advanced adenomas). Furthermore, the performance of NDKA was compared with the faecal immunochemical test (FIT). The study population included a case-control cohort and a screening cohort (511 asymptomatic first-degree relatives of CRC patients that underwent a colonoscopy and a FIT). Serum NDKA was elevated in CRC patients in the case-control cohort (p = 0.002). In the screening cohort, NDKA levels were higher for advanced adenomas (p = 0.010) and advanced neoplasia (p = 0.006) compared to no neoplasia. Moreover, elevated NDKA was associated with severe characteristics of adenomas (≥3 lesions, size ≥ 1 cm or villous component). Setting specificity to 85%, NDKA showed a sensitivity of 30.19% and 29.82% for advanced adenomas and advanced neoplasia, respectively. NDKA combined with FIT (100 ng/mL cut-off) detected advanced adenomas and advanced neoplasia with 45.28% and 49.12% sensitivity, with specificity close to 90%. The combination of serum NDKA and FIT can improve the detection of advanced neoplasia, mainly for lesions located on the proximal colon, in asymptomatic individuals with CRC family-risk.
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23
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Werner S, Chen H, Butt J, Michel A, Knebel P, Holleczek B, Zörnig I, Eichmüller SB, Jäger D, Pawlita M, Waterboer T, Brenner H. Evaluation of the diagnostic value of 64 simultaneously measured autoantibodies for early detection of gastric cancer. Sci Rep 2016; 6:25467. [PMID: 27140836 PMCID: PMC4853774 DOI: 10.1038/srep25467] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Accepted: 04/18/2016] [Indexed: 02/08/2023] Open
Abstract
Autoantibodies against tumor-associated antigens (TAAs) have been suggested as biomarkers for early detection of gastric cancer. However, studies that systematically assess the diagnostic performance of a large number of autoantibodies are rare. Here, we used bead-based multiplex serology to simultaneously measure autoantibody responses against 64 candidate TAAs in serum samples from 329 gastric cancer patients, 321 healthy controls and 124 participants with other diseases of the upper digestive tract. At 98% specificity, sensitivities for the 64 tested autoantibodies ranged from 0–12% in the training set and a combination of autoantibodies against five TAAs (MAGEA4 + CTAG1 + TP53 + ERBB2_C + SDCCAG8) was able to detect 32% of the gastric cancer patients at a specificity of 87% in the validation set. Sensitivities for early and late stage gastric cancers were similar, while chronic atrophic gastritis, a precursor lesion of gastric cancer, was not detectable. However, the 5-marker combination also detected 26% of the esophageal cancer patients. In conclusion, the tested autoantibodies and combinations alone did not reach sufficient sensitivity for gastric cancer screening. Nevertheless, some autoantibodies, such as anti-MAGEA4, anti-CTAG1 or anti-TP53 and their combinations could possibly contribute to the development of cancer early detection tests (not necessarily restricted to gastric cancer) when being combined with other markers.
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Affiliation(s)
- Simone Werner
- Division of Clinical Epidemiology and Aging Research, DKFZ, Heidelberg, Germany
| | - Hongda Chen
- Division of Clinical Epidemiology and Aging Research, DKFZ, Heidelberg, Germany
| | - Julia Butt
- Division of Molecular Diagnostics of Oncogenic Infections, DKFZ, Heidelberg, Germany
| | - Angelika Michel
- Division of Molecular Diagnostics of Oncogenic Infections, DKFZ, Heidelberg, Germany
| | - Phillip Knebel
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | | | - Inka Zörnig
- Department of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Heidelberg, Germany
| | - Stefan B Eichmüller
- GMP &T cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Dirk Jäger
- Department of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Heidelberg, Germany
| | - Michael Pawlita
- Division of Molecular Diagnostics of Oncogenic Infections, DKFZ, Heidelberg, Germany
| | - Tim Waterboer
- Division of Molecular Diagnostics of Oncogenic Infections, DKFZ, Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, DKFZ, Heidelberg, Germany.,Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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Prorok PC, Kramer BS, Miller AB. Study designs for determining and comparing sensitivities of disease screening tests. J Med Screen 2015; 22:213-20. [DOI: 10.1177/0969141315600003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Accepted: 07/21/2015] [Indexed: 11/16/2022]
Abstract
Objective To investigate the capability of various study designs to determine the sensitivity of a disease screening test. Methods Quantities that can be calculated from these designs were derived and examined for their relationship to true sensitivity (the ability to detect unrecognized disease that would surface clinically in the absence of screening) and overdiagnosis. Results To examine the sensitivity of one test, the single cohort design, in which all participants receive the test, is particularly weak, providing only an upper bound on the true sensitivity, and yields no information about overdiagnosis. A randomized design, with one control arm and participants tested in the other, that includes sufficient post-screening follow-up, allows calculation of bounds on, and an approximation to, true sensitivity and also determination of overdiagnosis. Without follow-up, bounds on the true sensitivity can be calculated. To compare two tests, the single cohort paired design in which all participants receive both tests is precarious. The three arm randomized design with post screening follow-up is preferred, yielding an approximation to the true sensitivity, bounds on the true sensitivity, and the extent of overdiagnosis of each test. Without post screening follow-up, bounds on the true sensitivities can be calculated. When an unscreened control arm is not possible, the two-arm randomized design is recommended. Individual test sensitivities cannot be determined, but with sufficient post-screening follow-up, an order relationship can be established, as can the difference in overdiagnosis between the two tests.
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Wang M, Yin B, Wang HY, Wang RF. Current advances in T-cell-based cancer immunotherapy. Immunotherapy 2015; 6:1265-78. [PMID: 25524383 DOI: 10.2217/imt.14.86] [Citation(s) in RCA: 109] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.
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Affiliation(s)
- Mingjun Wang
- Center for Inflammation & Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA
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Mordente A, Meucci E, Martorana GE, Silvestrini A. Cancer Biomarkers Discovery and Validation: State of the Art, Problems and Future Perspectives. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2015; 867:9-26. [DOI: 10.1007/978-94-017-7215-0_2] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Creaney J, Robinson BWS. Author's response: Inconsistent results or inconsistent methods? A plea for standardisation of biomarker sampling in mesothelioma studies. Thorax 2014; 70:374-5. [PMID: 25480441 DOI: 10.1136/thoraxjnl-2014-206564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- Jenette Creaney
- National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia The Australian Mesothelioma Tissue Bank, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - Bruce W S Robinson
- National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia The Australian Mesothelioma Tissue Bank, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
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Jordan R, Visweswaran S, Gopalakrishnan V. Semi-automated literature mining to identify putative biomarkers of disease from multiple biofluids. J Clin Bioinforma 2014; 4:13. [PMID: 25379168 PMCID: PMC4215335 DOI: 10.1186/2043-9113-4-13] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Accepted: 10/02/2014] [Indexed: 11/10/2022] Open
Abstract
Background Computational methods for mining of biomedical literature can be useful in augmenting manual searches of the literature using keywords for disease-specific biomarker discovery from biofluids. In this work, we develop and apply a semi-automated literature mining method to mine abstracts obtained from PubMed to discover putative biomarkers of breast and lung cancers in specific biofluids. Methodology A positive set of abstracts was defined by the terms ‘breast cancer’ and ‘lung cancer’ in conjunction with 14 separate ‘biofluids’ (bile, blood, breastmilk, cerebrospinal fluid, mucus, plasma, saliva, semen, serum, synovial fluid, stool, sweat, tears, and urine), while a negative set of abstracts was defined by the terms ‘(biofluid) NOT breast cancer’ or ‘(biofluid) NOT lung cancer.’ More than 5.3 million total abstracts were obtained from PubMed and examined for biomarker-disease-biofluid associations (34,296 positive and 2,653,396 negative for breast cancer; 28,355 positive and 2,595,034 negative for lung cancer). Biological entities such as genes and proteins were tagged using ABNER, and processed using Python scripts to produce a list of putative biomarkers. Z-scores were calculated, ranked, and used to determine significance of putative biomarkers found. Manual verification of relevant abstracts was performed to assess our method’s performance. Results Biofluid-specific markers were identified from the literature, assigned relevance scores based on frequency of occurrence, and validated using known biomarker lists and/or databases for lung and breast cancer [NCBI’s On-line Mendelian Inheritance in Man (OMIM), Cancer Gene annotation server for cancer genomics (CAGE), NCBI’s Genes & Disease, NCI’s Early Detection Research Network (EDRN), and others]. The specificity of each marker for a given biofluid was calculated, and the performance of our semi-automated literature mining method assessed for breast and lung cancer. Conclusions We developed a semi-automated process for determining a list of putative biomarkers for breast and lung cancer. New knowledge is presented in the form of biomarker lists; ranked, newly discovered biomarker-disease-biofluid relationships; and biomarker specificity across biofluids.
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Affiliation(s)
- Rick Jordan
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Shyam Visweswaran
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA ; Intelligent Systems Program, University of Pittsburgh, Pittsburgh, PA, USA ; Department of Computational & Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Vanathi Gopalakrishnan
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA ; Intelligent Systems Program, University of Pittsburgh, Pittsburgh, PA, USA ; Department of Computational & Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA
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Espín-Pérez A, Krauskopf J, de Kok TM, Kleinjans JC. ‘OMICS-based’ Biomarkers for Environmental Health Studies. Curr Environ Health Rep 2014. [DOI: 10.1007/s40572-014-0028-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Abstract
Recent developments and improvements of multimodal imaging methods for use in animal research have substantially strengthened the options of in vivo visualization of cancer-related processes over time. Moreover, technological developments in probe synthesis and labelling have resulted in imaging probes with the potential for basic research, as well as for translational and clinical applications. In addition, more sophisticated cancer models are available to address cancer-related research questions. This Review gives an overview of developments in these three fields, with a focus on imaging approaches in animal cancer models and how these can help the translation of new therapies into the clinic.
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Affiliation(s)
- Marion de Jong
- Departments of Nuclear Medicine and Radiology, Erasmus MC Rotterdam, Room Na-610, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
| | - Jeroen Essers
- Departments of Genetics (Cancer Genomics Centre), Radiation Oncology and Vascular Surgery, Erasmus MC Rotterdam, P.O Box 2040, 3000CA Rotterdam, The Netherlands
| | - Wytske M van Weerden
- Department of Urology, Erasmus MC Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
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Abstract
Liver fibrosis is the final common pathway for almost all causes of chronic liver injury. Liver fibrosis is now known to be a dynamic process having significant potential for resolution. Therefore, fibrosis prediction is an essential part of the assessment and management of patients with chronic liver disease. As such, there is strong demand for reliable liver biomarkers that provide insight into disease etiology, diagnosis, therapy, and prognosis in lieu of more invasive approaches such as liver biopsy. Current diagnostic strategies range from use of serum biomarkers to more advanced imaging techniques including transient elastography and magnetic resonance imaging. In addition to these modalities, there are other approaches including the use of novel, but yet to be validated, biomarkers. In this chapter, we discuss the biomarkers of liver fibrosis including the use of invasive and noninvasive biomarkers and disease-specific biomarkers in various chronic liver diseases.
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van Dieck J, Schmid V, Heindl D, Dziadek S, Schraeml M, Gerg M, Massoner P, Engel AM, Tiefenthaler G, Vural S, Stritt S, Tetzlaff F, Soukupova M, Kopetzki E, Bossenmaier B, Thomas M, Klein C, Mertens A, Heller A, Tacke M. Development of bispecific molecules for the in situ detection of protein-protein interactions and protein phosphorylation. ACTA ACUST UNITED AC 2014; 21:357-68. [PMID: 24529991 DOI: 10.1016/j.chembiol.2013.12.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2013] [Revised: 12/13/2013] [Accepted: 12/31/2013] [Indexed: 01/07/2023]
Abstract
Investigation of protein-protein interactions (PPIs) and protein phosphorylation in clinical tissue samples can offer valuable information about the activation status and function of proteins involved in disease progression. However, existing antibody-based methods for phosphorylation detection have been found to lack specificity, and methods developed for examining PPIs in vitro cannot be easily adapted for tissues samples. In this study, we eliminated some of these limitations by developing a specific immunohistochemical staining method that uses "dual binders" (DBs), which are bispecific detection agents consisting of two Fab fragment molecules joined by a flexible linker, to detect PPIs and protein phosphorylation. We engineered DBs by selecting Fab fragments with fast off-rate kinetics, which allowed us to demonstrate that stable target binding was achieved only upon simultaneous, cooperative binding to both epitopes. We show that DBs specifically detect the activated HER2/HER3 complex in formalin-fixed, paraffin-embedded cancer cells and exhibit superior detection specificity for phospho-HER3 compared to the corresponding monoclonal antibody. Overall, the performance of DBs makes them attractive tools for future development for clinical applications.
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Affiliation(s)
- Jan van Dieck
- Pharma Research and Early Development, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Volker Schmid
- Pharma Research and Early Development, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Dieter Heindl
- Roche Professional Diagnostics, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Sebastian Dziadek
- Roche Professional Diagnostics, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Michael Schraeml
- Roche Professional Diagnostics, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Michael Gerg
- Roche Professional Diagnostics, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Petra Massoner
- Roche Professional Diagnostics, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Alfred M Engel
- Roche Professional Diagnostics, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Georg Tiefenthaler
- Pharma Research and Early Development, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Serhat Vural
- Roche Professional Diagnostics, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Simon Stritt
- Pharma Research and Early Development, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Fabian Tetzlaff
- Pharma Research and Early Development, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Monika Soukupova
- Roche Professional Diagnostics, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Erhard Kopetzki
- Pharma Research and Early Development, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Birgit Bossenmaier
- Pharma Research and Early Development, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Marlene Thomas
- Pharma Research and Early Development, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Christian Klein
- Pharma Research and Early Development, Roche Glycart AG, 8952 Schlieren, Switzerland
| | - Alfred Mertens
- Pharma Research and Early Development, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Astrid Heller
- Pharma Research and Early Development, Roche Diagnostics GmbH, 82377 Penzberg, Germany
| | - Michael Tacke
- Roche Professional Diagnostics, Roche Diagnostics GmbH, 82377 Penzberg, Germany.
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Fung KYC, Nice E, Priebe I, Belobrajdic D, Phatak A, Purins L, Tabor B, Pompeia C, Lockett T, Adams TE, Burgess A, Cosgrove L. Colorectal cancer biomarkers: To be or not to be? Cautionary tales from a road well travelled. World J Gastroenterol 2014; 20:888-898. [PMID: 24574763 PMCID: PMC3921542 DOI: 10.3748/wjg.v20.i4.888] [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: 09/26/2013] [Revised: 11/26/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide and places a major economic burden on the global health care system. The time frame for development from premalignant to malignant disease typically spans 10-15 years, and this latent period provides an ideal opportunity for early detection and intervention to improve patient outcomes. Currently, early diagnosis of CRC is hampered by a lack of suitable non-invasive biomarkers that are clinically or economically acceptable for population-based screening. New blood-based protein biomarkers for early detection of CRC are therefore urgently required. The success of clinical biomarker discovery and validation studies is critically dependent on understanding and adjusting for potential experimental, analytical, and biological factors that can interfere with the robust interpretation of results. In this review we outline some important considerations for research groups undertaking biomarker research with exemplars from our studies. Implementation of experimental strategies to minimise the potential effects of these problems will facilitate the identification of panels of biomarkers with the sensitivity and specificity required for the development of successful tests for the early detection and surveillance of CRC.
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Anderson D, Kodukula K. Biomarkers in pharmacology and drug discovery. Biochem Pharmacol 2014; 87:172-88. [DOI: 10.1016/j.bcp.2013.08.026] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Accepted: 08/19/2013] [Indexed: 12/21/2022]
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Prassas I, Brinc D, Farkona S, Leung F, Dimitromanolakis A, Chrystoja CC, Brand R, Kulasingam V, Blasutig IM, Diamandis EP. False biomarker discovery due to reactivity of a commercial ELISA for CUZD1 with cancer antigen CA125. Clin Chem 2013; 60:381-8. [PMID: 24097894 DOI: 10.1373/clinchem.2013.215236] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND By using proteomics and bioinformatics, we have previously identified a group of highly pancreas-specific proteins as candidate pancreatic ductal adenocarcinoma (PDAC) biomarkers. With the use of commercially available ELISAs, the performance of some of these candidates was initially evaluated in a relatively small serum cohort (n = 100 samples). This phase revealed that CUB and zona pellucida-like domains protein 1 (CUZD1) may represent a new, promising PDAC biomarker. METHODS We performed detailed experiments to investigate the specificity of the commercial CUZD1 ELISA assay. CUZD1 was expressed in house in both bacteria and yeast expression systems. Recombinant CUZD1 and biological samples containing CUZD1, as well as commercial CUZD1 ELISA standards, were analyzed by Western blot, size exclusion HPLC, and mass spectrometry (LC-MS Orbitrap). RESULTS We confirmed that instead of CUZD1, the commercial assay is recognizing a nonhomologous, known cancer antigen [cancer antigen 125 (CA125)]. CONCLUSIONS We conclude that poor characterization of commercial ELISA assays is a factor that could lead to false biomarker discovery. To our knowledge, this is the first report documenting that a commercial ELISA marketed for one analyte (CUZD1) may, in fact, recognize a different, nonhomologous antigen (CA125).
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Affiliation(s)
- Ioannis Prassas
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
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Han SS, Lee SJ, Kim WJ, Ryu DR, Won JY, Park S, Cheon MJ. Plasma osteopontin is a useful diagnostic biomarker for advanced non-small cell lung cancer. Tuberc Respir Dis (Seoul) 2013; 75:104-10. [PMID: 24101934 PMCID: PMC3790021 DOI: 10.4046/trd.2013.75.3.104] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2013] [Revised: 05/10/2013] [Accepted: 05/31/2013] [Indexed: 01/01/2023] Open
Abstract
Background Osteopontin (OPN) and carbonic anhydrase IX (CAIX), which are expressed on the surface of tumor cells, are associated with hypoxia during tumor development and progression. However, the roles of these proteins in the plasma of patients with non-small cell lung cancer (NSCLC) are poorly understood. Herein, we hypothesized that plasma OPN and CAIX levels could be used as diagnostic and prognostic tumor markers in patients with NSCLC. Methods Fifty-three patients with NSCLC and 50 healthy control subjects were enrolled. We selected controls without malignancy and matched them with NSCLC patient cases according to age and gender. Blood samples were collected at the time of diagnosis; the plasma levels of OPN and CAIX were measured by enzyme-linked immunosorbent assays. Results The plasma levels of OPN in the patients with NSCLC were significantly elevated as compared to those in the controls (p=0.016). However, there was no difference in the plasma level of CAIX between the NSCLC patients and controls. NSCLC patients with a distant metastasis had a remarkable increase in plasma OPN compared with patients without metastasis (p=0.026), but no such correlation was found for CAIX. There was no difference in overall survival rates according to the plasma level of OPN between the two groups (by Kaplan-Meier survival analysis). Conclusion Plasma OPN levels were elevated in patients with NSCLC as compared with the controls, with greater elevation of OPN levels in the advanced stages of disease. Therefore, plasma OPN may have utility as a diagnostic, but not prognostic, biomarker of advanced NSCLC.
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Affiliation(s)
- Seon-Sook Han
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
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Neto BAD, Corrêa JR, Silva RG. Selective mitochondrial staining with small fluorescent probes: importance, design, synthesis, challenges and trends for new markers. RSC Adv 2013. [DOI: 10.1039/c2ra21995f] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Abstract
BACKGROUND
The National Cancer Institute's Early Detection Research Network (EDRN) has made significant progress in developing an organized effort for discovering and validating biomarkers, building resources to support this effort, demonstrating the capabilities of several genomic and proteomic platforms, identifying candidate biomarkers, and undertaking multicenter validation studies. In its first 10 years, the EDRN went from a groundbreaking concept to an operational success.
CONTENTS
The EDRN has established clear milestones for reaching a decision of “go” or “no go” during the biomarker development process. Milestones are established on the basis of statistical criteria, performance characteristics of biomarkers, and anticipated clinical use. More than 300 biomarkers have been stopped from further development. To date, the EDRN has prioritized more than 300 biomarkers and has completed more than 10 validation studies. The US Food and Drug Administration has now cleared 5 biomarkers for various clinical endpoints.
SUMMARY
The EDRN today combines numerous collaborative and multidisciplinary investigator-initiated projects with a strong national administrative and data infrastructure. The EDRN has created a rigorous peer-review system that ensures that preliminary data—analytical, clinical, and quantitative—are of excellent quality. The process begins with an internal review with clinical, biostatistical, and analytical expertise. The project then receives external peer review and, finally, National Cancer Institute program staff review, resulting in an exceptionally robust and high-quality validation trial.
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Affiliation(s)
- Sudhir Srivastava
- Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD
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Immunohistochemical markers of the hypoxic response can identify malignancy in phaeochromocytomas and paragangliomas and optimize the detection of tumours with VHL germline mutations. Br J Cancer 2012; 108:429-37. [PMID: 23257898 PMCID: PMC3566818 DOI: 10.1038/bjc.2012.538] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background: There are no reliable markers of malignancy in phaeochromocytomas (PCC) and paragangliomas (PGL). We investigated the relevance of the mammalian target of rapamycin (mTOR)/AKT and hypoxic pathways as novel immunohistochemical markers of malignancy. Methods: Tissue microarray blocks were constructed with a total of 100 tumours (10 metastatic) and 20 normal adrenomedullary samples. Sections were immunostained for hypoxia-inducible factor 1α (Hif-1α), vascular endothelial growth factor A (VEGF-A), mTOR, carbonic anhydrase IX (CaIX) and AKT. The predictive performance of these markers was studied using univariate, multivariate and receiver operating characteristic analyses. Results: In all, 100 consecutive patients, 64% PCC, 29% familial with a median tumour size of 4.7 cm (range 1–14) were included. Univariate analyses showed Hif-1α overexpression, tumour necrosis, size >5 cm, capsular and vascular invasion to be predictors of metastasis. In multivariate analysis, Hif-1α, necrosis and vascular invasion remained as independent predictors of metastasis. Hif-1α was the most discriminatory biomarker for the presence of metastatic diffusion. Strong membranous CaIX expression was seen in von Hippel–Lindau (VHL) PCC as opposed to other subtypes. Conclusion: Lack of vascular invasion, tumour necrosis and low Hif-1α expression identify tumours with lower risk of malignancy. We propose membranous CaIX expression as a potential marker for VHL disease in patients presenting with PCC.
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Qian M, Wu D, Wang E, Marincola FM, Wang W, Rhodes W, Liebman M, Bai C, Lam CW, Marko-Varga G, Fehniger TE, Andersson R, Wang X. Development and promotion in translational medicine: perspectives from 2012 sino-american symposium on clinical and translational medicine. Clin Transl Med 2012; 1:25. [PMID: 23369198 PMCID: PMC3561049 DOI: 10.1186/2001-1326-1-25] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2012] [Accepted: 09/11/2012] [Indexed: 11/10/2022] Open
Abstract
UNLABELLED BACKGROUND Clinical translational medicine (CTM) is an emerging area comprising multidisciplinary research from basic science to medical applications and entails a close collaboration among hospital, academia and industry. FINDINGS This Session focused discussing on new models for project development and promotion in translational medicine. The conference stimulated the scientific and commercial communication of project development between academies and companies, shared the advanced knowledge and expertise of clinical applications, and created the environment for collaborations. CONCLUSIONS Although strategic collaborations between corporate and academic institutions have resulted in a state of resurgence in the market, new cooperation models still need time to tell whether they will improve the translational medicine process.
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Younes A, Berry DA. From drug discovery to biomarker-driven clinical trials in lymphoma. Nat Rev Clin Oncol 2012; 9:643-53. [PMID: 22965151 DOI: 10.1038/nrclinonc.2012.156] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Over the past three decades, the pathological classification of lymphoma has substantially improved. The early Rappaport classification included a handful of subtypes that did not reflect the cell of origin and, not surprisingly, resulted in diagnostic inaccuracies. The WHO currently classifies lymphoma into 30 major distinctive types. While this classification improved the accuracy and consistency of the histological diagnosis of lymphoma, it had little impact on advancing drug development or improving the cure rate of this disease. One reason for this lack of improvement is that recent developments in cancer genomics show these histopathological subtypes to be heterogeneous. Basing treatment decisions on histopathological subtypes is inefficient as it groups different underlying molecular characteristics into one category. Such a strategy exposes many patients to potentially toxic drugs without providing benefits. The recent approval of two new cancer drugs with companion diagnostics to allow selection and treatment of patients with melanoma and non-small-cell lung cancer has raised hope that a similar approach may also expedite successful drug development in lymphoma. We review the current status of biomarker development in lymphoma, and discuss novel biomarker-directed clinical trial designs for lymphoma.
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Affiliation(s)
- Anas Younes
- Department of Lymphoma/Myeloma, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
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Frangogiannis NG. Biomarkers: hopes and challenges in the path from discovery to clinical practice. Transl Res 2012; 159:197-204. [PMID: 22424424 PMCID: PMC4402218 DOI: 10.1016/j.trsl.2012.01.023] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2012] [Accepted: 01/25/2012] [Indexed: 01/08/2023]
Abstract
Biomarkers are objectively measured indicators of normal or pathological processes that may be helpful in diagnosis, staging, monitoring treatment, or prognostic evaluation of a disease. Although development of genomic, metabolomic and proteomic technologies has contributed to an explosion in identification of candidate analytes, validation remains expensive and challenging, and successful introduction of new biomarkers to clinical practice occurs at a very slow pace. The goal of this introductory overview is to provide the context for a series of review manuscripts published in the special issue on biomarkers. The promises and challenges of biomarker discovery are highlighted. Discovery and implementation of transformative new biomarkers in clinical practice requires close collaborations between scientists, clinicians and industry. High throughput technologies can identify a myriad of promising candidates but cannot predict their clinical value. In addition to rapid effective and systematic approaches for clinical validation, there is a need to study and establish links between the purported biomarker and the pathophysiologic basis of the disease of interest. Biomarkers are most informative when they provide insights into activation of specific pathways, thus serving as windows into the molecular basis of the disease.
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Affiliation(s)
- Nikolaos G Frangogiannis
- Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, NY
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