Journal

Talanta

Papers (17)

Enhancing endometrial cancer detection: Blood serum intrinsic fluorescence data processing and machine learning application

Endometrial cancer (EC) is the most prevalent cancer within the female reproductive system in developed countries. Despite its high incidence, there is currently no established laboratory screening test for EC, making early detection challenging. This study introduces an innovative, minimally invasive, and cost-effective method utilizing three-dimensional fluorescence analysis combined with machine learning algorithms to enhance early EC detection. Intrinsic fluorescence of blood serum samples was measured using a luminescence spectrophotometer, which captured fluorescence spectra as synchronous excitation spectra and visualized them through wavelength contour matrices. The spectral data were processed using machine learning algorithms, including Random Forest (RF), Logistic Regression (LR), Support Vector Machine (SVM), and Stochastic Gradient Descent (SGD), along with exploratory techniques such as Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA). Fluorescence ratios R300/330 and R360/490, indicative of altered tryptophan metabolism and redox state changes, were identified as fluorescent spectral markers and represent key metabolic biomarkers. These ratios demonstrated high diagnostic efficacy with AUC values of 0.88 and 0.91, respectively. Among the ML algorithms, LR and RF exhibited high sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), showing significant promise for clinical application. After optimization, LR achieved a sensitivity of 0.94, specificity of 0.89, and an impressive AUC value of 0.94. The application of this novel approach in laboratory diagnostics has the potential to significantly enhance early detection and improve prognosis for EC patients.

A perspective on the potential use of aptamer-based field-effect transistor sensors as biosensors for ovarian cancer biomarkers CA125 and HE4

Ovarian cancer (OC) is one of the most fatal gynaecological malignancies, primarily because of its typically asymptomatic early stages, which complicates early detection. Therefore, developing sensitive and appropriate biomarkers for efficient diagnosis of OC is urgently needed. Aptamers, short sequences of single-stranded DNA or RNA molecules, have become crucial in tumor diagnosis because of their high affinity for specific molecules produced by tumors. This ability allows aptamers to accurately detect OC, thus providing better survival rates and a reduced disease burden. Biosensors that combine recognition molecules and nanomaterials are essential in various fields, including disease diagnosis and health management. Molecular-specific field-effect transistor (FET) biosensors are particularly promising due to their rapid response times, ease of miniaturization, and high sensitivity in detecting OC. Aptamers, which are known for their stability and structural tunability, are increasingly being used as biological recognition units in FET biosensors, offering selective and high-affinity binding to target molecules that are ideal for medical diagnostics. This review explores the recent advancements in biosensors for OC detection, including FET biosensors with aptamer-functionalized nanomaterials for CA125 and HE4. Furthermore, this review provides an overview of the structure and sensing principles of these advanced biosensors, preparation methods and functionalization strategies that enhance their performance. Additionally, notable progress and potential of biosensors, including aptamer-functionalized FET biosensors for OC diagnosis have been summarized, emphasising their role and clinical validation in advancing medical diagnostics and improving patient outcomes through enhanced detection capabilities.

Detection of high-risk HPV 16 genotypes in cervical cancers using isothermal DNA amplification with electrochemical genosensor

Cervical cancer emerges as the third most prevalent types of malignancy among women on a global scale. Cervical cancer is significantly associated with the persistent infection of human papillomavirus (HPV) type 16. The process of diagnosing is crucial in order to prevent the progression of a condition into a malignant state. The early detection of cervical cancer through initial stage screening is of the utmost significance in both the prevention and effective management of this disease. The present detection methodology is dependent on quantitative polymerase chain reaction (qPCR), which necessitates the use of a costly heat cycler instrument. In this study, we report the development of an electrochemical DNA biosensor integrated with an isothermal recombinase polymerase amplification (RPA) reaction for the detection and identification of the high-risk HPV-16 genotype. The electrochemical biosensor exhibited a high degree of specificity and sensitivity, as evidenced by its limit of detection (LOD) of 0.23 copies/μL of HPV-16 DNA. The validity of this electrochemical platform was confirmed through the analysis of 40 cervical tissues samples, and the findings were consistent with those obtained through polymerase chain reaction (PCR) testing. Our straightforward electrochemical detection technology and quick turnaround time at 75 min make the assay suitable for point-of-care testing in low-resource settings.

Non-invasive screening for ovarian cancer by combining serum SERS with interpretable machine learning models

Early identification of malignant ovarian tumors is critical for informing treatment decisions and enhancing patients' quality of life. As the third most prevalent gynecologic cancer globally, ovarian cancer remains challenging to diagnose due to the high cost, limited accessibility, and radiation exposure associated with current screening techniques. This study integrates surface-enhanced Raman spectroscopy (SERS) with feature selection techniques and deep learning frameworks to construct a diagnostic model for detecting ovarian cancer based on serum component analysis. The goal is to realize efficient and precise non-invasive screening for the disease. High-quality SERS spectra were first collected from serum samples of patients with clinically confirmed ovarian cancer, healthy individuals, and those with ovarian endometrioma. Subsequently, the Light Gradient Boosting Machine (LightGBM) algorithm was employed as the base classifier to perform two-stage feature selection, utilizing both the model's intrinsic feature importance scores and SHapley Additive exPlanation (SHAP) values. Finally, a Deep Neural Network (DNN) was incorporated and trained via backpropagation to optimize the weights and biases of neuronal connections, thereby improving the predictive performance of the overall network model. After feature selection, the DNN algorithm achieved an accuracy rate of 92.03% in the five-fold cross-validation for the three types of recognition - healthy individuals, ovarian cancer, and potentially malignant ovarian endometrioma. In the evaluation of the independent test set, the accuracy rate still reached as high as 86.96%. In addition, compared with traditional machine learning algorithms, the classification performance of DNN is also the best. The findings above demonstrate that the integration of serum SERS with the robust LightGBM-DNN algorithm offers a promising strategy for clinical ovarian cancer screening.

Metaproteomic analysis from cervical biopsies and cytologies identifies proteinaceous biomarkers representing both human and microbial species

The detection of HPV infection and microbial colonization in cervical lesions is currently done through PCR-based viral or bacterial DNA amplification. Our objective was to develop a methodology to expand the metaproteomic landscape of cervical disease and determine if protein biomarkers from both human and microbes could be detected in distinct cervical samples. This would lead to the development of multi-species proteomics, which includes protein-based lateral flow diagnostics that can define patterns of microbes and/or human proteins relevant to disease status. In this study, we collected both non-frozen tissue biopsy and exfoliative non-fixed cytology samples to assess the consistency of detecting human proteomic signatures between the cytology and biopsy samples. Our results show that proteomics using biopsies or cytologies can detect both human and microbial organisms. Across patients, Lumican and Galectin-1 were most highly expressed human proteins in the tissue biopsy, whilst IL-36 and IL-1RA were most highly expressed human proteins in the cytology. We also used mass spectrometry to assess microbial proteomes known to reside based on prior 16S rRNA gene signatures. Lactobacillus spp. was the most highly expressed proteome in patient samples and specific abundant Lactobacillus proteins were identified. These methodological approaches can be used in future metaproteomic clinical studies to interrogate the vaginal human and microbiome structure and metabolic diversity in cytologies or biopsies from the same patients who have pre-invasive cervical intraepithelial neoplasia, invasive cervical cancer, as well as in healthy controls to assess how human and pathogenic proteins may correlate with disease presence and severity.

Publisher

Elsevier BV

ISSN

0039-9140