RESUMO
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.
Assuntos
Antígeno Ca-125/metabolismo , Carcinoma Epitelial do Ovário/patologia , Transformação Celular Neoplásica/patologia , Proteínas de Membrana/metabolismo , Neoplasias Ovarianas/patologia , Antígeno Ca-125/genética , Carcinoma Epitelial do Ovário/imunologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/imunologia , Progressão da Doença , Feminino , Técnicas de Silenciamento de Genes , Glicosilação , Humanos , Proteínas de Membrana/genética , Neoplasias Ovarianas/imunologia , Ovário/citologia , Ovário/imunologia , Ovário/patologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Evasão TumoralRESUMO
This study demonstrates a discrimination of endometrial cancer versus (non-cancerous) benign controls based on mid-infrared (MIR) spectroscopy of dried plasma or serum liquid samples. A detailed evaluation was performed using four discriminant methods (LDA, QDA, kNN or SVM) to execute the classification task. The discriminant methods used in the study comprised methods that are widely used in the statistics (LDA and QDA) and machine learning literature (kNN and SVM). Of particular interest, is the impact of discrimination when presented with spectral data from a section of the bio-fingerprint region (1430 cm-1 to 900 cm-1) in contrast to the more extended bio-fingerprint region used here (1800 cm-1 to 900 cm-1). Quality metrics used were the misclassification rate, sensitivity, specificity, and Matthew's correlation coefficient (MCC). For plasma (with spectral data ranging from 1430 cm-1 to 900 cm-1), the best performing classifier was kNN, which achieved a sensitivity, specificity and MCC of 0.865 ± 0.043, 0.865 ± 0.023 and 0.762 ± 0.034, respectively. For serum (in the same wavenumber range), the best performing classifier was LDA, achieving a sensitivity, specificity and MCC of 0.899 ± 0.023, 0.763 ± 0.048 and 0.664 ± 0.067, respectively. For plasma (with spectral data ranging from 1800 cm-1 to 900 cm-1), the best performing classifier was SVM, with a sensitivity, specificity and MCC of 0.993 ± 0.010, 0.815 ± 0.000 and 0.815 ± 0.010, respectively. For serum (in the same wavenumber range), QDA performed best achieving a sensitivity, specificity and MCC of 0.852 ± 0.023, 0.700 ± 0.162 and 0.557 ± 0.012, respectively. Our findings demonstrate that even when a section of the bio-fingerprint region has been removed, good classification of endometrial cancer versus non-cancerous controls is still maintained. These findings suggest the potential of a MIR screening tool for endometrial cancer screening.
Assuntos
Neoplasias do Endométrio , Detecção Precoce de Câncer , Neoplasias do Endométrio/diagnóstico , Feminino , Humanos , Aprendizado de Máquina , SoroRESUMO
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.
Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Antígeno Ca-125/sangue , Antígeno Ca-125/urina , Proteínas de Membrana/sangue , Proteínas de Membrana/urina , Neoplasias Ovarianas/diagnóstico , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Estudos de Casos e Controles , Quimioterapia Adjuvante , Estudos de Coortes , Feminino , Humanos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/urinaRESUMO
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.
Assuntos
Líquido Ascítico/química , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Análise Espectral Raman/métodos , Adulto , Idoso , Algoritmos , Estudos de Casos e Controles , Análise Discriminante , Feminino , Humanos , Pessoa de Meia-Idade , Plasma , Análise de Componente Principal , Sensibilidade e Especificidade , Soro , Máquina de Vetores de SuporteRESUMO
Raman hyperspectral imaging is a powerful technique that provides both chemical and spatial information of a sample matrix being studied. The generated data are composed of three-dimensional (3D) arrays containing the spatial information across the x- and y-axis, and the spectral information in the z-axis. Unfolding procedures are commonly employed to analyze this type of data in a multivariate fashion, where the spatial dimension is reshaped and the spectral data fits into a two-dimensional (2D) structure and, thereafter, common first-order chemometric algorithms are applied to process the data. There are only a few algorithms capable of working with the full 3D array. Herein, we propose new algorithms for 3D discriminant analysis of hyperspectral images based on a three-dimensional principal component analysis linear discriminant analysis (3D-PCA-LDA) and a three-dimensional discriminant analysis quadratic discriminant analysis (3D-PCA-QDA) approach. The analysis was performed in order to discriminate simulated and real-world data, comprising benign controls and ovarian cancer samples based on Raman hyperspectral imaging, in which 3D-PCA-LDA and 3D-PCA-QDA achieved far superior performance than classical algorithms using unfolding procedures (PCA-LDA, PCA-QDA, partial lest squares discriminant analysis [PLS-DA], and support vector machines [SVM]), where the classification accuracies improved from 66% to 83% (simulated data) and from 50% to 100% (real-world dataset) after employing the 3D techniques. 3D-PCA-LDA and 3D-PCA-QDA are new approaches for discriminant analysis of hyperspectral images multisets to provide faster and superior classification performance than traditional techniques.
Assuntos
Algoritmos , Máquina de Vetores de Suporte , Análise Discriminante , Análise de Componente PrincipalRESUMO
The progressive aging of the world's population makes a higher prevalence of neurodegenerative diseases inevitable. The necessity for an accurate, but at the same time, inexpensive and minimally invasive, diagnostic test is urgently required, not only to confirm the presence of the disease but also to discriminate between different types of dementia to provide the appropriate management and treatment. In this study, attenuated total reflection FTIR (ATR-FTIR) spectroscopy combined with chemometric techniques were used to analyze blood plasma samples from our cohort. Blood samples are easily collected by conventional venepuncture, permitting repeated measurements from the same individuals to monitor their progression throughout the years or evaluate any tested drugs. We included 549 individuals: 347 with various neurodegenerative diseases and 202 age-matched healthy individuals. Alzheimer's disease (AD; n = 164) was identified with 70% sensitivity and specificity, which after the incorporation of apolipoprotein ε4 genotype (APOE ε4) information, increased to 86% when individuals carried one or two alleles of ε4, and to 72% sensitivity and 77% specificity when individuals did not carry ε4 alleles. Early AD cases (n = 14) were identified with 80% sensitivity and 74% specificity. Segregation of AD from dementia with Lewy bodies (DLB; n = 34) was achieved with 90% sensitivity and specificity. Other neurodegenerative diseases, such as frontotemporal dementia (FTD; n = 30), Parkinson's disease (PD; n = 32), and progressive supranuclear palsy (PSP; n = 31), were included in our cohort for diagnostic purposes. Our method allows for both rapid and robust diagnosis of neurodegeneration and segregation between different dementias.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Apolipoproteína E4/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodosRESUMO
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 (â¼780-1858 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.
Assuntos
Imageamento Tridimensional , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico por imagem , Análise de Componente Principal , Estudos de Casos e Controles , Feminino , Humanos , Análise Espectral RamanRESUMO
The current lack of an accurate, cost-effective and non-invasive test that would allow for screening and diagnosis of gynaecological carcinomas, such as endometrial and ovarian cancer, signals the necessity for alternative approaches. The potential of spectroscopic techniques in disease investigation and diagnosis has been previously demonstrated. Here, we used attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy to analyse urine samples from women with endometrial (n = 10) and ovarian cancer (n = 10), as well as from healthy individuals (n = 10). After applying multivariate analysis and classification algorithms, biomarkers of disease were pointed out and high levels of accuracy were achieved for both endometrial (95% sensitivity, 100% specificity; accuracy: 95%) and ovarian cancer (100% sensitivity, 96.3% specificity; accuracy 100%). The efficacy of this approach, in combination with the non-invasive method for urine collection, suggest a potential diagnostic tool for endometrial and ovarian cancers.
Assuntos
Neoplasias do Endométrio/diagnóstico , Neoplasias Ovarianas/diagnóstico , Espectroscopia de Infravermelho com Transformada de Fourier , Urinálise/métodos , Testes Diagnósticos de Rotina , Neoplasias do Endométrio/urina , Feminino , Humanos , Análise Multivariada , Neoplasias Ovarianas/urina , Sensibilidade e EspecificidadeRESUMO
Alzheimer's disease (AD) is currently under-diagnosed and is predicted to affect a great number of people in the future, due to the unrestrained aging of the population. An accurate diagnosis of AD at an early stage, prior to (severe) symptomatology, is of crucial importance as it would allow the subscription of effective palliative care and/or enrolment into specific clinical trials. Today, new analytical methods and research initiatives are being developed for the on-time diagnosis of this devastating disorder. During the last decade, spectroscopic techniques have shown great promise in the robust diagnosis of various pathologies, including neurodegenerative diseases and dementia. In the current study, blood plasma samples were analysed with near-infrared (NIR) spectroscopy as a minimally-invasive method to distinguish patients with AD (n = 111) from non-demented volunteers (n = 173). After applying multivariate classification models (principal component analysis with quadratic discriminant analysis - PCA-QDA), AD individuals were correctly identified with 92.8% accuracy, 87.5% sensitivity and 96.1% specificity. Our results show the potential of NIR spectroscopy as a simple and cost-effective diagnostic tool for AD. Robust and early diagnosis may be a first step towards tackling this disease by allowing timely intervention.
Assuntos
Doença de Alzheimer/diagnóstico , Análise Química do Sangue/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Idoso , Análise Discriminante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente PrincipalRESUMO
The cyclical process of regeneration of the endometrium suggests that it may contain a cell population that can provide daughter cells with high proliferative potential. These cell lineages are clinically significant as they may represent clonogenic cells that may also be involved in tumourigenesis as well as endometriotic lesion development. To determine whether the putative stem cell location within human uterine tissue can be derived using vibrational spectroscopy techniques, normal endometrial tissue was interrogated by two spectroscopic techniques. Paraffin-embedded uterine tissues containing endometrial glands were sectioned to 10-µm-thick parallel tissue sections and were floated onto BaF2 slides for synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy and globar focal plane array-based FTIR spectroscopy. Different spectral characteristics were identified depending on the location of the glands examined. The resulting infrared spectra were subjected to multivariate analysis to determine associated biophysical differences along the length of longitudinal and crosscut gland sections. Comparison of the epithelial cellular layer of transverse gland sections revealed alterations indicating the presence of putative transient-amplifying-like cells in the basalis and mitotic cells in the functionalis. SR-FTIR microspectroscopy of the base of the endometrial glands identified the location where putative stem cells may reside at the same time pointing towards νsPO2- in DNA and RNA, nucleic acids and amide I and II vibrations as major discriminating factors. This study supports the view that vibration spectroscopy technologies are a powerful adjunct to our understanding of the stem cell biology of endometrial tissue. Graphical abstract á .
Assuntos
Endométrio/química , Células Epiteliais/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Células-Tronco/química , Adulto , Endométrio/citologia , Células Epiteliais/citologia , Desenho de Equipamento , Feminino , Humanos , Análise Multivariada , Espectroscopia de Infravermelho com Transformada de Fourier/instrumentação , Células-Tronco/citologia , SíncrotronsRESUMO
Mitochondrial diseases have been extensively investigated over the last three decades, but many questions regarding their underlying aetiologies remain unanswered. Mitochondrial dysfunction is not only responsible for a range of neurological and myopathy diseases but also considered pivotal in a broader spectrum of common diseases such as epilepsy, autism and bipolar disorder. These disorders are a challenge to diagnose and treat, as their aetiology might be multifactorial. In this review, the focus is placed on potential mechanisms capable of introducing defects in mitochondria resulting in disease. Special attention is given to the influence of xenobiotics on mitochondria; environmental factors inducing mutations or epigenetic changes in the mitochondrial genome can alter its expression and impair the whole cell's functionality. Specifically, we suggest that environmental agents can cause damage in mitochondrial DNA and consequently lead to mutagenesis. Moreover, we describe current approaches for handling mitochondrial diseases, as well as available prenatal diagnostic tests, towards eliminating these maternally inherited diseases. Undoubtedly, more research is required, as current therapeutic approaches mostly employ palliative therapies rather than targeting primary mechanisms or prophylactic approaches. Much effort is needed into further unravelling the relationship between xenobiotics and mitochondria, as the extent of influence in mitochondrial pathogenesis is increasingly recognised.
Assuntos
Genoma Mitocondrial , Doenças Mitocondriais/genética , Mutagênese , Pesquisa Translacional Biomédica , Animais , Poluentes Ambientais , Epigênese Genética , Humanos , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/etiologiaRESUMO
Surgical management of ovarian tumours largely depends on their histo-pathological diagnosis. Currently, screening for ovarian malignancy with tumour markers in conjunction with radiological investigations has a low specificity for discriminating benign from malignant tumours. Also, pre-operative biopsy of ovarian masses increases the risk of intra-peritoneal dissemination of malignancy. Intra-operative frozen section, although sufficiently accurate in differentiating tumours according to their histological type, increases operation times. This results in increased surgery-related risks to the patient and additional burden to resource allocation. We set out to determine whether attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, combined with chemometric analysis can be applied to discriminate between normal, borderline and malignant ovarian tumours and classify ovarian carcinoma subtypes according to the unique spectral signatures of their molecular composition. Formalin-fixed, paraffin-embedded ovarian tissue blocks were de-waxed, mounted on Low-E slides and desiccated before being analysed using ATR-FTIR spectroscopy. Chemometric analysis in the form of principal component analysis (PCA), successive projection algorithm (SPA) and genetic algorithm (GA), followed by linear discriminant analysis (LDA) of the obtained spectra revealed clear segregation between benign versus borderline versus malignant tumours as well as segregation between different histological tumour subtypes, when these approaches are used in combination. ATR-FTIR spectroscopy coupled with chemometric analysis has the potential to provide a novel diagnostic approach in the accurate diagnosis of ovarian tumours assisting surgical decision making to avoid under-treatment or over-treatment, with minimal impact to the patient.
Assuntos
Análise de Fourier , Informática/métodos , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/patologia , Ovário/citologia , Ovário/patologia , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Algoritmos , Metabolismo dos Carboidratos , DNA/metabolismo , Análise Discriminante , Feminino , Humanos , Metabolismo dos Lipídeos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo , Ovário/metabolismo , Fosfatos/metabolismo , Análise de Componente Principal , Proteínas/metabolismo , RNA/metabolismoRESUMO
As biospectroscopy techniques continue to be developed for screening or diagnosis within a point-of-care setting, an important development for this field will be high-throughput optimization. For many of these techniques, it is therefore necessary to adapt and develop parameters to generate a robust yet simple approach delivering high-quality spectra from biological samples. Specifically, this is important for surface-enhanced Raman spectroscopy (SERS) wherein there are multiple variables that can be optimised to achieve an enhancement of the Raman signal from a sample. One hypothesis is that "large" diameter (>100 nm) gold nanoparticles provide a greater enhancement at near-infrared (NIR) and infrared (IR) wavelengths than those <100 nm in diameter. Herein, we examine this notion using examples in which SERS spectra were acquired from MCF-7 breast cancer cells incubated with 150 nm gold nanoparticles. It was found that 150 nm gold nanoparticles are an excellent material for NIR/IR SERS. Larger gold nanoparticles may better satisfy the theoretical restraints for SERS enhancement at NIR/IR wavelengths compared to smaller nanoparticles. Also, larger nanoparticles or their aggregates are more readily observed via optical microscopy (and especially electron microscopy) compared to smaller ones. This allows rapid and straightforward identification of target areas containing a high concentration of nanoparticles and facilitating SERS spectral acquisition. To some extent, these observations appear to extend to biofluids such as blood plasma or (especially) serum; SERS spectra of such biological samples often exhibit a low signal-to-noise ratio in the absence of nanoparticles. With protein-rich biofluids such as serum, a dramatic SERS effect can be observed; although this might facilitate improved spectral biomarker identification in the future, it may not always improve classification between control vs. cancer. Thus, use of "large" gold nanoparticles are a good starting point in order to derive informative NIR/IR SERS analysis of biological samples.
Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Ouro/análise , Nanopartículas Metálicas/análise , Análise Espectral Raman/métodos , Mama/química , Neoplasias da Mama/química , Feminino , Ouro/sangue , Humanos , Células MCF-7 , Nanopartículas Metálicas/ultraestrutura , Soro/químicaRESUMO
Currently available screening tests do not deliver the required sensitivity and specificity for accurate diagnosis of ovarian or endometrial cancer. Infrared (IR) spectroscopy of blood plasma or serum is a rapid, versatile, and relatively non-invasive approach which could characterize biomolecular alterations due to cancer and has potential to be utilized as a screening or diagnostic tool. In the past, no such approach has been investigated for its applicability in screening and/or diagnosis of gynaecological cancers. We set out to determine whether attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy coupled with a proposed classification machine could be applied to IR spectra obtained from plasma and serum for accurate class prediction (cancer vs. normal). Plasma and serum samples were obtained from ovarian cancer cases (n = 30), endometrial cancer cases (n = 30) and non-cancer controls (n = 30), and subjected to ATR-FTIR spectroscopy. Four derived datasets were processed to estimate the real-world diagnosis of ovarian and endometrial cancer. Classification results for ovarian cancer were remarkable (up to 96.7%), whereas endometrial cancer was classified with a relatively high accuracy (up to 81.7%). The results from different combinations of feature extraction and classification methods, and also classifier ensembles, were compared. No single classification system performed best for all different datasets. This demonstrates the need for a framework that can accommodate a diverse set of analytical methods in order to be adaptable to different datasets. This pilot study suggests that ATR-FTIR spectroscopy of blood is a robust tool for accurate diagnosis, and carries the potential to be utilized as a screening test for ovarian cancer in primary care settings. The proposed classification machine is a powerful tool which could be applied to classify the vibrational spectroscopy data of different biological systems (e.g., tissue, urine, saliva), with their potential application in clinical practice.
Assuntos
Células Sanguíneas/patologia , Neoplasias do Endométrio/diagnóstico , Neoplasias Ovarianas/diagnóstico , Ovário/patologia , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Máquina de Vetores de Suporte , Idoso , Estudos de Casos e Controles , Detecção Precoce de Câncer , Neoplasias do Endométrio/sangue , Feminino , Humanos , Análise dos Mínimos Quadrados , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Projetos Piloto , Análise de Componente PrincipalRESUMO
Cervical cancer screening programmes have greatly reduced the burden associated with this disease. However, conventional cervical cytology screening still lacks sensitivity and specificity. There is an urgent need for the development of a low-cost robust screening technique. By generating a spectral "biochemical-cell fingerprint", Fourier-transform infrared (FTIR) spectroscopy has been touted as a tool capable of segregating grades of dysplasia. A total of 529 specimens were collected over a period of one year at two colposcopy centres in Dublin, Ireland. Of these, n = 128 were conventionally classed as high-grade, n = 186 as low-grade and n = 215 as normal. Following FTIR spectroscopy, derived spectra were examined for segregation between classes in scores plots generated with subsequent multivariate analysis. A degree of crossover between classes was noted and this could be associated with imperfect conventional screening resulting in an inaccurate diagnosis or an incomplete transition between classes. Maximal crossover associated with n = 102 of 390 specimens analyzed was found between normal and low-grade specimens. However, robust spectral differences (P≤ 0.0001) were still observed at 1512 cm(-1), 1331 cm(-1) and 937 cm(-1). For high-grade vs. low-grade specimens, spectral differences (P≤ 0.0001) were observed at Amide I (1624 cm(-1)), Amide II (1551 cm(-1)) and asymmetric phosphate stretching vibrations (νasPO2(-); 1215 cm(-1)). Least crossover (n = 50 of 343 specimens analyzed) was seen when comparing high-grade vs. normal specimens; significant inter-class spectral differences (P≤ 0.0001) were noted at Amide II (1547 cm(-1)), 1400 cm(-1) and 995 cm(-1). Deeper understanding of the underlying changes in the transition between cervical cytology classes (normal vs. low-grade vs. high-grade) is required in order to develop biospectroscopy tools as a screening approach. This will then allow for the development of blind classification algorithms.
Assuntos
Colo do Útero/patologia , Citodiagnóstico , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Neoplasias do Colo do Útero/diagnóstico , Estudos de Casos e Controles , Colposcopia , Detecção Precoce de Câncer , Feminino , Humanos , Análise dos Mínimos Quadrados , Gradação de Tumores , Estadiamento de Neoplasias , Análise de Componente Principal , Esfregaço VaginalRESUMO
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.
Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/epidemiologia , Qualidade de Vida , Infecções por Papillomavirus/complicações , Detecção Precoce de Câncer , Análise Espectral , Programas de Rastreamento/métodos , Aprendizado de MáquinaRESUMO
Biospectroscopy is employed to derive absorbance spectra representative of biomolecules present in biological samples. The mid-infrared region (λ = 2.5 µm-25 µm) is absorbed to give a biochemical-cell fingerprint (v = 1800-900 cm(-1)). Cellular material produces complex spectra due to the variety of chemical bonds present. The complexity and size of spectral data sets warrant multivariate analysis for data reduction, interpretation, and classification. Various multivariate analyses are available including principal component analysis (PCA), partial least-squares (PLS), linear discriminant analysis (LDA), and evolving fuzzy rule-based classifier (eClass). Interpretation of both visual and numerical results facilitates biomarker identification, cell-type discrimination, and predictive and mechanistic understanding of cellular behavior. Biospectroscopy is a high-throughput nondestructive technology. A comparison of biomarkers/mechanistic knowledge determined from conventional approaches to biospectroscopy coupled with multivariate analysis often provides complementary answers and a novel approach for diagnosis of disease and cell biology.
Assuntos
Biomarcadores/análise , Biologia Computacional/métodos , Estrutura Molecular , Análise Espectral/métodos , Análise por Conglomerados , Análise Discriminante , Análise dos Mínimos Quadrados , Análise Multivariada , Análise de Componente PrincipalRESUMO
Approaches that allow one to rapidly understand tissue structure and functionality in situ remain to be developed. Such techniques are required in many instances, including where there is a need to remove with a high degree of confidence positive tumour margins during surgical excision. As biological tissue has little contrast, gold standard confirmation of surgical margins is conventionally undertaken by histopathological diagnosis of tissue architecture via optical microscopy. Vibrational spectroscopy techniques, when coupled to sophisticated computational analyses, are capable of constructing bio-molecular contrast images of unstained tissue. To assess the relative applicability of a range of candidate algorithms to distinguish the in situ bio-molecular structures of a complex tissue, the empty modelling approach of multivariate curve resolution-alternating least squares (MCR-ALS) was compared to hierarchical cluster analysis (HCA) or principal component analysis (PCA). Such chemometric analyses were applied to Raman images of benign (tumour-adjacent) endometrium, stage I and stage II endometrioid cancer. Re-constructed images from the in situ bio-molecular tissue architectures highlighted features associated with glandular epithelium, stroma, glandular lumen and myometrium. Of the tested chemometric analyses, MCR-ALS provided the best bio-molecular contrast images, superior to those derived following HCA or PCA, with clear and defined margins of histological features. Iteratively-resolved spectra identified wavenumbers responsible for the contrast image. Wavenumbers 1234 cm(-1) (Amide III), 1390 cm(-1) (CH(3) bend), 1675 cm(-1) (Amide I/lipid), 1275 cm(-1) (Amide III), 918 cm(-1) (proline) and 936 cm(-1) (proline, valine and proteins) were responsible for generating the majority of the contrast within MCR-ALS-generated images. Applications of sophisticated computational analyses coupled with vibrational spectroscopy techniques have the potential to lend novel functionality insights into bio-molecular structures in vivo.