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Article ; Online: The evolving role of MUC16 (CA125) in the transformation of ovarian cells and the progression of neoplasia.

Giamougiannis, Panagiotis / Martin-Hirsch, Pierre L / Martin, Francis L

2021 Volume 42, Issue 3, Page(s) 327–343

Abstract: MUC16 (the cancer antigen CA125) is the most commonly used serum biomarker in epithelial ovarian cancer, with increasing levels reflecting disease progression. It is a transmembrane glycoprotein with multiple isoforms, undergoing significant changes ... ...

Abstract	MUC16 (the cancer antigen CA125) is the most commonly used serum biomarker in epithelial ovarian cancer, with increasing levels reflecting disease progression. It is a transmembrane glycoprotein with multiple isoforms, undergoing significant changes through the metastatic process. Aberrant glycosylation and cleavage with overexpression of a small membrane-bound fragment consist MUC16-related mechanisms that enhance malignant potential. Even MUC16 knockdown can induce an aggressive phenotype but can also increase susceptibility to chemotherapy. Variable MUC16 functions help ovarian cancer cells avoid immune cytotoxicity, survive inside ascites and form metastases. This review provides a comprehensive insight into MUC16 transformations and interactions, with description of activated oncogenic signalling pathways, and adds new elements on the role of its differential glycosylation. By following the journey of the molecule from pre-malignant states to advanced stages of disease it demonstrates its behaviour, in relation to the phenotypic shifts and progression of ovarian cancer. Additionally, it presents proposed differences of MUC16 structure in normal/benign conditions and epithelial ovarian malignancy.
MeSH term(s)	CA-125 Antigen/genetics ; CA-125 Antigen/metabolism ; Carcinoma, Ovarian Epithelial/immunology ; Carcinoma, Ovarian Epithelial/pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/immunology ; Cell Transformation, Neoplastic/pathology ; Disease Progression ; Female ; Gene Knockdown Techniques ; Glycosylation ; Humans ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Ovarian Neoplasms/immunology ; Ovarian Neoplasms/pathology ; Ovary/cytology ; Ovary/immunology ; Ovary/pathology ; Signal Transduction/genetics ; Signal Transduction/immunology ; Tumor Escape
Chemical Substances	CA-125 Antigen ; MUC16 protein, human ; Membrane Proteins
Language	English
Publishing date	2021-02-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	603134-1
ISSN	1460-2180 ; 0143-3334
ISSN (online)	1460-2180
ISSN	0143-3334
DOI	10.1093/carcin/bgab010
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Article ; Online: Advancing cervical cancer diagnosis and screening with spectroscopy and machine learning.

Meza Ramirez, Carlos A / Greenop, Michael / Almoshawah, Yasser A / Martin Hirsch, Pierre L / Rehman, Ihtesham U

Expert review of molecular diagnostics

2023 Volume 23, Issue 5, Page(s) 375–390

Abstract: Introduction: In the UK alone, the incidence of cervical cancer is increasing, hence an urgent need for early and rapid detection of cancer before it develops. Spectroscopy in conjunction with machine learning offers a disruptive technology that ... ...

Abstract	Introduction: In the UK alone, the incidence of cervical cancer is increasing, hence an urgent need for early and rapid detection of cancer before it develops. Spectroscopy in conjunction with machine learning offers a disruptive technology that promises to pick up cancer early as compared to the current diagnostic techniques used. Areas covered: This review article explores the different spectroscopy techniques that have been used for the analysis of cervical cancer. Along with the extensive description of spectroscopic techniques, the various machine learning techniques are also described as well as the applications that have been explored in the diagnosis of cervical cancer. This review delimits the literature specifically associated with cervical cancer studies performed solely with the use of a spectroscopy technique, and machine learning. Expert opinion: Although there are several methods and techniques to detect cervical cancer, the clinical sector requires to introduce new diagnostic technologies that help improve the quality of life of patients. These innovative technologies involve spectroscopy as a qualitative method and machine learning as a quantitative method. In this article, both the techniques and methodologies that allow and promise to be a new screening tool for the detection of cervical cancer are covered.
MeSH term(s)	Female ; Humans ; Uterine Cervical Neoplasms/epidemiology ; Quality of Life ; Papillomavirus Infections/complications ; Early Detection of Cancer ; Spectrum Analysis ; Mass Screening/methods ; Machine Learning
Language	English
Publishing date	2023-04-19
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	2112530-2
ISSN	1744-8352 ; 1473-7159
ISSN (online)	1744-8352
ISSN	1473-7159
DOI	10.1080/14737159.2023.2203816
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Article ; Online: Need for early, minimally invasive cancer diagnosis.

Paraskevaidi, Maria / Martin-Hirsch, Pierre L / Martin, Francis L

Proceedings of the National Academy of Sciences of the United States of America

2019 Volume 116, Issue 11, Page(s) 4752

MeSH term(s)	Humans ; Microscopy, Confocal ; Neoplasms ; Tumor Microenvironment
Language	English
Publishing date	2019-02-19
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1817551116
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Article ; Online: Vibrational spectroscopy: a promising approach to discriminate neurodegenerative disorders.

Paraskevaidi, Maria / Martin-Hirsch, Pierre L / Martin, Francis L

Molecular neurodegeneration

2018 Volume 13, Issue 1, Page(s) 20

Abstract: Neurodegenerative diseases are a growing burden in modern society, thus crucially calling for the development of accurate diagnostic strategies. These diseases are currently incurable, a fact which has been attributed to their late diagnosis, after brain ...

Abstract	Neurodegenerative diseases are a growing burden in modern society, thus crucially calling for the development of accurate diagnostic strategies. These diseases are currently incurable, a fact which has been attributed to their late diagnosis, after brain damage has already become widespread. An earlier and improved diagnosis is necessary for the enrolment of patients into clinical trials and can pave the way for the development of therapeutic tactics. Novel analytical techniques, such as mass spectrometry and vibrational spectroscopy, have been able to successfully detect and characterise neurodegenerative disorders. It is critical to globally support and make use of innovative basic research and techniques, which could ultimately lead to the creation of a cost-effective diagnostic test. Minimally invasive samples, such as biological fluids, have also been shown to reveal information for these diseases; utilising them could simplify sample collection/analysis and be more preferable to patients.
MeSH term(s)	Humans ; Neurodegenerative Diseases/diagnosis ; Spectrum Analysis/methods
Language	English
Publishing date	2018-05-02
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	2244557-2
ISSN	1750-1326 ; 1750-1326
ISSN (online)	1750-1326
ISSN	1750-1326
DOI	10.1186/s13024-018-0252-x
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Article ; Online: Progress and Challenges in the Diagnosis of Dementia: A Critical Review.

Paraskevaidi, Maria / Martin-Hirsch, Pierre L / Martin, Francis L

ACS chemical neuroscience

2018 Volume 9, Issue 3, Page(s) 446–461

Abstract: Longer life expectancies have led to an increased number of neurodegenerative disease cases globally. Accurate diagnosis of this devastating disorder is of crucial importance but is still feasible only by a brain biopsy after death. An enormous amount of ...

Abstract	Longer life expectancies have led to an increased number of neurodegenerative disease cases globally. Accurate diagnosis of this devastating disorder is of crucial importance but is still feasible only by a brain biopsy after death. An enormous amount of attention and research has been in place over the years toward the better understanding of the mechanisms, as well as the early diagnosis, of neurodegeneration. However, numerous studies have been contradictory from time to time, while new diagnostic methods are constantly developed in a tireless effort to tackle the disease. Nonetheless, there is not yet a conclusive report covering a broader range of techniques for the diagnosis of different types of dementia. In this paper, we critically review current knowledge on the different hypotheses about the pathogenesis of distinct types of dementia, as well as risk factors and current diagnostic approaches in a clinical setting, including neuroimaging, cerebrospinal (CSF), and blood tests. Encouraging research results for the diagnosis and investigation of neurodegenerative disorders are also reported. Particular attention is given to the field of spectroscopy as an emerging tool to detect dementias, follow-up patients, and potentially monitor the patients' response to a therapeutic approach. Spectroscopic techniques, such as infrared and Raman spectroscopy, have facilitated numerous disease-related studies, including neurodegenerative disorders, and are currently undergoing trials for clinical implementation. This review constitutes a comprehensive report with an in-depth focus on promising imaging, molecular biomarker and spectroscopic tests in the field of dementive diseases.
MeSH term(s)	Alzheimer Disease/diagnosis ; Alzheimer Disease/pathology ; Animals ; Biomarkers/analysis ; Dementia/diagnosis ; Dementia/pathology ; Humans ; Neuroimaging ; Risk ; Spectrum Analysis, Raman/methods
Chemical Substances	Biomarkers
Language	English
Publishing date	2018-02-12
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.8b00007
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Article: Detection of ovarian cancer (± neo-adjuvant chemotherapy effects) via ATR-FTIR spectroscopy: comparative analysis of blood and urine biofluids in a large patient cohort

Giamougiannis, Panagiotis / Morais, Camilo L. M. / Rodriguez, Brice / Wood, Nicholas J. / Martin-Hirsch, Pierre L. / Martin, Francis L.

Analytical and bioanalytical chemistry. 2021 Aug., v. 413, no. 20

2021

Abstract: Ovarian cancer remains the most lethal gynaecological malignancy, as its timely detection at early stages remains elusive. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy of biofluids has been previously applied in pilot ... ...

Abstract	Ovarian cancer remains the most lethal gynaecological malignancy, as its timely detection at early stages remains elusive. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy of biofluids has been previously applied in pilot studies for ovarian cancer diagnosis, with promising results. Herein, these initial findings were further investigated by application of ATR-FTIR spectroscopy in a large patient cohort. Spectra were obtained by measurements of blood plasma and serum, as well as urine, from 116 patients with ovarian cancer and 307 patients with benign gynaecological conditions. A preliminary chemometric analysis revealed significant spectral differences in ovarian cancer patients without previous chemotherapy (n = 71) and those who had received neo-adjuvant chemotherapy—NACT (n = 45), so these groups were compared separately with benign controls. Classification algorithms with blind predictive model validation demonstrated that serum was the best biofluid, achieving 76% sensitivity and 98% specificity for ovarian cancer detection, whereas urine exhibited poor performance. A drop in sensitivities for the NACT ovarian cancer group in plasma and serum indicates the potential of ATR-FTIR spectroscopy to identify chemotherapy-related spectral changes. Comparisons of regression coefficient plots for identification of biomarkers suggest that glycoproteins (such as CA125) are the main classifiers for ovarian cancer detection and responsible for smaller differences in spectra between NACT patients and benign controls. This study confirms the capacity of biofluids’ ATR-FTIR spectroscopy (mainly blood serum) to diagnose ovarian cancer with high accuracy and demonstrates its potential in monitoring response to chemotherapy, which is reported for the first time. ATR-FTIR spectroscopy of blood serum achieves good segregation of ovarian cancers from benign controls, with attenuation of differences following neo-adjuvant chemotherapy.
Keywords	biomarkers ; blood serum ; chemometrics ; drug therapy ; glycoproteins ; model validation ; ovarian neoplasms ; patients ; regression analysis ; urine
Language	English
Dates of publication	2021-08
Size	p. 5095-5107.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ISSN	1618-2642
DOI	10.1007/s00216-021-03472-8
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Article ; Online: A three-dimensional principal component analysis approach for exploratory analysis of hyperspectral data: identification of ovarian cancer samples based on Raman microspectroscopy imaging of blood plasma.

Morais, Camilo L M / Martin-Hirsch, Pierre L / Martin, Francis L

The Analyst

2019 Volume 144, Issue 7, Page(s) 2312–2319

Abstract: Hyperspectral imaging is a powerful tool to obtain both chemical and spatial information of biological systems. However, few algorithms are capable of working with full three-dimensional images, in which reshaping or averaging procedures are often ... ...

Abstract	Hyperspectral imaging is a powerful tool to obtain both chemical and spatial information of biological systems. However, few algorithms are capable of working with full three-dimensional images, in which reshaping or averaging procedures are often performed to reduce the data complexity. Herein, we propose a new algorithm of three-dimensional principal component analysis (3D-PCA) for exploratory analysis of complete 3D spectrochemical images obtained through Raman microspectroscopy. Blood plasma samples of ten patients (5 healthy controls, 5 diagnosed with ovarian cancer) were analysed by acquiring hyperspectral imaging in the fingerprint region (∼780-1858 cm-1). Results show that 3D-PCA can clearly differentiate both groups based on its scores plot, where higher loadings coefficients were observed in amino acids, lipids and DNA regions. 3D-PCA is a new methodology for exploratory analysis of hyperspectral imaging, providing fast information for class differentiation.
MeSH term(s)	Case-Control Studies ; Female ; Humans ; Imaging, Three-Dimensional ; Ovarian Neoplasms/blood ; Ovarian Neoplasms/diagnostic imaging ; Principal Component Analysis ; Spectrum Analysis, Raman
Language	English
Publishing date	2019-02-04
Publishing country	England
Document type	Journal Article
ZDB-ID	210747-8
ISSN	1364-5528 ; 0003-2654
ISSN (online)	1364-5528
ISSN	0003-2654
DOI	10.1039/c8an02031k
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Article ; Online: Detection of ovarian cancer (± neo-adjuvant chemotherapy effects) via ATR-FTIR spectroscopy: comparative analysis of blood and urine biofluids in a large patient cohort.

Giamougiannis, Panagiotis / Morais, Camilo L M / Rodriguez, Brice / Wood, Nicholas J / Martin-Hirsch, Pierre L / Martin, Francis L

Analytical and bioanalytical chemistry

2021 Volume 413, Issue 20, Page(s) 5095–5107

Abstract	Ovarian cancer remains the most lethal gynaecological malignancy, as its timely detection at early stages remains elusive. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy of biofluids has been previously applied in pilot studies for ovarian cancer diagnosis, with promising results. Herein, these initial findings were further investigated by application of ATR-FTIR spectroscopy in a large patient cohort. Spectra were obtained by measurements of blood plasma and serum, as well as urine, from 116 patients with ovarian cancer and 307 patients with benign gynaecological conditions. A preliminary chemometric analysis revealed significant spectral differences in ovarian cancer patients without previous chemotherapy (n = 71) and those who had received neo-adjuvant chemotherapy-NACT (n = 45), so these groups were compared separately with benign controls. Classification algorithms with blind predictive model validation demonstrated that serum was the best biofluid, achieving 76% sensitivity and 98% specificity for ovarian cancer detection, whereas urine exhibited poor performance. A drop in sensitivities for the NACT ovarian cancer group in plasma and serum indicates the potential of ATR-FTIR spectroscopy to identify chemotherapy-related spectral changes. Comparisons of regression coefficient plots for identification of biomarkers suggest that glycoproteins (such as CA125) are the main classifiers for ovarian cancer detection and responsible for smaller differences in spectra between NACT patients and benign controls. This study confirms the capacity of biofluids' ATR-FTIR spectroscopy (mainly blood serum) to diagnose ovarian cancer with high accuracy and demonstrates its potential in monitoring response to chemotherapy, which is reported for the first time. ATR-FTIR spectroscopy of blood serum achieves good segregation of ovarian cancers from benign controls, with attenuation of differences following neo-adjuvant chemotherapy.
MeSH term(s)	Biomarkers, Tumor/blood ; Biomarkers, Tumor/urine ; CA-125 Antigen/blood ; CA-125 Antigen/urine ; Case-Control Studies ; Chemotherapy, Adjuvant ; Cohort Studies ; Female ; Humans ; Membrane Proteins/blood ; Membrane Proteins/urine ; Ovarian Neoplasms/blood ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/urine ; Spectroscopy, Fourier Transform Infrared/methods
Chemical Substances	Biomarkers, Tumor ; CA-125 Antigen ; MUC16 protein, human ; Membrane Proteins
Language	English
Publishing date	2021-07-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	201093-8
ISSN	1618-2650 ; 0016-1152 ; 0372-7920
ISSN (online)	1618-2650
ISSN	0016-1152 ; 0372-7920
DOI	10.1007/s00216-021-03472-8
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Article: A comparative analysis of different biofluids towards ovarian cancer diagnosis using Raman microspectroscopy

Giamougiannis, Panagiotis / Morais, Camilo L. M / Grabowska, Rita / Ashton, Katherine M / Wood, Nicholas J / Martin-Hirsch, Pierre L / Martin, Francis L

Analytical and bioanalytical chemistry. 2021 Jan., v. 413, no. 3

2021

Abstract: Biofluids, such as blood plasma or serum, are currently being evaluated for cancer detection using vibrational spectroscopy. These fluids contain information of key biomolecules, such as proteins, lipids, carbohydrates and nucleic acids, that comprise ... ...

Abstract	Biofluids, such as blood plasma or serum, are currently being evaluated for cancer detection using vibrational spectroscopy. These fluids contain information of key biomolecules, such as proteins, lipids, carbohydrates and nucleic acids, that comprise spectrochemical patterns to differentiate samples. Raman is a water-free and practically non-destructive vibrational spectroscopy technique, capable of recording spectrochemical fingerprints of biofluids with minimum or no sample preparation. Herein, we compare the performance of these two common biofluids (blood plasma and serum) together with ascitic fluid, towards ovarian cancer detection using Raman microspectroscopy. Samples from thirty-eight patients were analysed (n = 18 ovarian cancer patients, n = 20 benign controls) through different spectral pre-processing and discriminant analysis techniques. Ascitic fluid provided the best class separation in both unsupervised and supervised discrimination approaches, where classification accuracies, sensitivities and specificities above 80% were obtained, in comparison to 60–73% with plasma or serum. Ascitic fluid appears to be rich in collagen information responsible for distinguishing ovarian cancer samples, where collagen-signalling bands at 1004 cm⁻¹ (phenylalanine), 1334 cm⁻¹ (CH₃CH₂ wagging vibration), 1448 cm⁻¹ (CH₂ deformation) and 1657 cm⁻¹ (Amide I) exhibited high statistical significance for class differentiation (P < 0.001). The efficacy of vibrational spectroscopy, in particular Raman spectroscopy, combined with ascitic fluid analysis, suggests a potential diagnostic method for ovarian cancer. Raman microspectroscopy analysis of ascitic fluid allows for discrimination of patients with benign gynaecological conditions or ovarian cancer.
Keywords	Raman spectroscopy ; analytical chemistry ; blood serum ; collagen ; deformation ; diagnostic techniques ; discriminant analysis ; ovarian neoplasms ; phenylalanine ; vibration
Language	English
Dates of publication	2021-01
Size	p. 911-922.
Publishing place	Springer Berlin Heidelberg
Document type	Article
Note	NAL-AP-2-clean
ISSN	1618-2642
DOI	10.1007/s00216-020-03045-1
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Article ; Online: An analysis of benign human prostate offers insights into the mechanism of apocrine secretion and the origin of prostasomes.

Fullwood, Nigel J / Lawlor, Alan J / Martin-Hirsch, Pierre L / Matanhelia, Shyam S / Martin, Francis L

Scientific reports

2019 Volume 9, Issue 1, Page(s) 4582

Abstract: The structure and function of normal human prostate is still not fully understood. Herein, we concentrate on the different cell types present in normal prostate, describing some previously unreported types and provide evidence that prostasomes are ... ...

Abstract	The structure and function of normal human prostate is still not fully understood. Herein, we concentrate on the different cell types present in normal prostate, describing some previously unreported types and provide evidence that prostasomes are primarily produced by apocrine secretion. Patients (n = 10) undergoing TURP were prospectively consented based on their having a low risk of harbouring CaP. Scanning electron microscopy and transmission electron microscopy was used to characterise cell types and modes of secretion. Zinc levels were determined using Inductively Coupled Plasma Mass Spectrometry. Although merocrine secretory cells were noted, the majority of secretory cells appear to be apocrine; for the first time, we clearly show high-resolution images of the stages of aposome secretion in human prostate. We also report a previously undescribed type of epithelial cell and the first ultrastructural image of wrapping cells in human prostate stroma. The zinc levels in the tissues examined were uniformly high and X-ray microanalysis detected zinc in merocrine cells but not in prostasomes. We conclude that a significant proportion of prostasomes, possibly the majority, are generated via apocrine secretion. This finding provides an explanation as to why so many large proteins, without a signal peptide sequence, are present in the prostatic fluid.
MeSH term(s)	Biological Transport ; Humans ; Male ; Models, Biological ; Prostate/metabolism ; Prostate/pathology ; Prostate/ultrastructure ; Secretory Vesicles/metabolism ; Secretory Vesicles/ultrastructure
Language	English
Publishing date	2019-03-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-40820-2
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