Search Results (9)

To investigate the incidence and prognostically significant correlations and cooperations of LKB1 loss of expression in non-small cell lung cancer (NSCLC), surgical specimens from 188 metastatic and 60 non-metastatic operable stage I-IIIA NSCLC patients were analyzed to evaluate their expression of LKB1 and pAMPK proteins in relation to various processes. The investigated factors included antitumor immunity response regulators STING and PD-L1; pro-angiogenic, EMT and cell cycle targets, as well as metastasis-related (VEGFC, PDGFRα, PDGFRβ, p53, p16, Cyclin D1, ZEB1, CD24) targets; and cell adhesion (β-catenin) molecules. The protein expression levels were evaluated via immunohistochemistry; the RNA levels of LKB1 and NEDD9 were evaluated via PCR, while KRAS exon 2 and BRAF^V600E mutations were evaluated by Sanger sequencing. Overall, loss of LKB1 protein expression was observed in 21% (51/248) patients and correlated significantly with histotype (p < 0.001), KRAS mutations (p < 0.001), KC status (concomitant KRAS mutation and p16 downregulation) (p < 0.001), STING loss (p < 0.001), and high CD24 expression (p < 0.001). STING loss also correlated significantly with loss of LKB1 expression in the metastatic setting both overall (p = 0.014) and in lung adenocarcinomas (LUACs) (p = 0.005). Additionally, LKB1 loss correlated significantly with a lack of or low β-catenin membranous expression exclusively in LUACs, both independently of the metastatic status (p = 0.019) and in the metastatic setting (p = 0.007). Patients with tumors yielding LKB1 loss and concomitant nonexistent or low β-catenin membrane expression experienced significantly inferior median overall survival of 20.50 vs. 52.99 months; p < 0.001 as well as significantly greater risk of death (HR: 3.32, 95% c.i.: 1.71–6.43; p <0.001). Our findings underscore the impact of the synergy of LKB1 with STING and β-catenin in NSCLC, in prognosis. Full article

Cardiotoxicity induced by breast cancer therapies is a potentially serious complication associated with the use of various breast cancer therapies. Prediction and better management of cardiotoxicity in patients receiving chemotherapy is of critical importance. However, the management of cancer therapy-related cardiac dysfunction (CTRCD) lacks clinical evidence and is based on limited clinical studies. Aim: To provide an overview of existing and potentially novel biomarkers that possess a promising predictive value for the early and late onset of CTRCD in the clinical setting. Methods: A systematic review of published studies searching for promising biomarkers for the prediction of CTRCD in patients with breast cancer was undertaken according to PRISMA guidelines. A search strategy was performed using PubMed, Google Scholar, and Scopus for the period 2013–2023. All subjects were >18 years old, diagnosed with breast cancer, and received breast cancer therapies. Results: The most promising biomarkers that can be used for the development of an alternative risk cardiac stratification plan for the prediction and/or early detection of CTRCD in patients with breast cancer were identified. Conclusions: We highlighted the new insights associated with the use of currently available biomarkers as a standard of care for the management of CTRCD and identified potentially novel clinical biomarkers that could be further investigated as promising predictors of CTRCD. Full article

Radiomics analysis is a powerful tool aiming to provide diagnostic and prognostic patient information directly from images that are decoded into handcrafted features, comprising descriptors of shape, size and textural patterns. Although radiomics is gaining momentum since it holds great promise for accelerating digital diagnostics, it is susceptible to bias and variation due to numerous inter-patient factors (e.g., patient age and gender) as well as inter-scanner ones (different protocol acquisition depending on the scanner center). A variety of image and feature based harmonization methods has been developed to compensate for these effects; however, to the best of our knowledge, none of these techniques has been established as the most effective in the analysis pipeline so far. To this end, this review provides an overview of the challenges in optimizing radiomics analysis, and a concise summary of the most relevant harmonization techniques, aiming to provide a thorough guide to the radiomics harmonization process. Full article

The tumor immune microenvironment (TIME) is an important player in breast cancer pathophysiology. Surrogates for antitumor immune response have been explored as predictive biomarkers to immunotherapy, though with several limitations. Immunohistochemistry for programmed death ligand 1 suffers from analytical problems, immune signatures are devoid of spatial information and histopathological evaluation of tumor infiltrating lymphocytes exhibits interobserver variability. Towards improved understanding of the complex interactions in TIME, several emerging multiplex in situ methods are being developed and gaining much attention for protein detection. They enable the simultaneous evaluation of multiple targets in situ, detection of cell densities/subpopulations as well as estimations of functional states of immune infiltrate. Furthermore, they can characterize spatial organization of TIME—by cell-to-cell interaction analyses and the evaluation of distribution within different regions of interest and tissue compartments—while digital imaging and image analysis software allow for reproducibility of the various assays. In this review, we aim to provide an overview of the different multiplex in situ methods used in cancer research with special focus on breast cancer TIME at the neoadjuvant, adjuvant and metastatic setting. Spatial heterogeneity of TIME and importance of longitudinal evaluation of TIME changes under the pressure of therapy and metastatic progression are also addressed. Full article

Pollen identification is an important task for the botanical certification of honey. It is performed via thorough microscopic examination of the pollen present in honey; a process called melissopalynology. However, manual examination of the images is hard, time-consuming and subject to inter- and intra-observer variability. In this study, we investigated the applicability of deep learning models for the classification of pollen-grain images into 20 pollen types, based on the Cretan Pollen Dataset. In particular, we applied transfer and ensemble learning methods to achieve an accuracy of 97.5%, a sensitivity of 96.9%, a precision of 97%, an F1 score of 96.89% and an AUC of 0.9995. However, in a preliminary case study, when we applied the best-performing model on honey-based pollen-grain images, we found that it performed poorly; only 0.02 better than random guessing (i.e., an AUC of 0.52). This indicates that the model should be further fine-tuned on honey-based pollen-grain images to increase its effectiveness on such data. Full article

The aim of this study is to investigate the possibility of predicting histological grade in patients with endometrial cancer on the basis of intravoxel incoherent motion (IVIM)-related histogram analysis parameters. This prospective study included 52 women with endometrial cancer (EC) who underwent MR imaging as initial staging in our hospital, allocated into low-grade (G1 and G2) and high-grade (G3) tumors according to the pathology reports. Regions of interest (ROIs) were drawn on the diffusion weighted images and apparent diffusion coefficient (ADC), true diffusivity (D), and perfusion fraction (f) using diffusion models were computed. Mean, median, skewness, kurtosis, and interquartile range (IQR) were calculated from the whole-tumor histogram. The IQR of the diffusion coefficient (D) was significantly lower in the low-grade tumors from that of the high-grade group with an adjusted p-value of less than 5% (0.048). The ROC curve analysis results of the statistically significant IQR of the D yielded an accuracy, sensitivity, and specificity of 74.5%, 70.1%, and 76.5% respectively, for discriminating low from high-grade tumors, with an optimal cutoff of 0.206 (×10⁻³ mm²/s) and an AUC of 75.4% (95% CI: 62.1 to 88.8). The IVIM modeling coupled with histogram analysis techniques is promising for preoperative differentiation between low- and high-grade EC tumors. Full article

Differentiation between transient osteoporosis (TOH) and avascular necrosis (AVN) of the hip is a longstanding challenge in musculoskeletal radiology. The purpose of this study was to utilize MRI-based radiomics and machine learning (ML) for accurate differentiation between the two entities. A total of 109 hips with TOH and 104 hips with AVN were retrospectively included. Femoral heads and necks with segmented radiomics features were extracted. Three ML classifiers (XGboost, CatBoost and SVM) using 38 relevant radiomics features were trained on 70% and validated on 30% of the dataset. ML performance was compared to two musculoskeletal radiologists, a general radiologist and two radiology residents. XGboost achieved the best performance with an area under the curve (AUC) of 93.7% (95% CI from 87.7 to 99.8%) among ML models. MSK radiologists achieved an AUC of 90.6% (95% CI from 86.7% to 94.5%) and 88.3% (95% CI from 84% to 92.7%), respectively, similar to residents. The general radiologist achieved an AUC of 84.5% (95% CI from 80% to 89%), significantly lower than of XGboost (p = 0.017). In conclusion, radiomics-based ML achieved a performance similar to MSK radiologists and significantly higher compared to general radiologists in differentiating between TOH and AVN. Full article

To address the current lack of dynamic susceptibility contrast magnetic resonance imaging (DSC–MRI)-based radiomics to predict isocitrate dehydrogenase (IDH) mutations in gliomas, we present a multicenter study that featured an independent exploratory set for radiomics model development and external validation using two independent cohorts. The maximum performance of the IDH mutation status prediction on the validation set had an accuracy of 0.544 (Cohen’s kappa: 0.145, F1-score: 0.415, area under the curve-AUC: 0.639, sensitivity: 0.733, specificity: 0.491), which significantly improved to an accuracy of 0.706 (Cohen’s kappa: 0.282, F1-score: 0.474, AUC: 0.667, sensitivity: 0.6, specificity: 0.736) when dynamic-based standardization of the images was performed prior to the radiomics. Model explainability using local interpretable model-agnostic explanations (LIME) and Shapley additive explanations (SHAP) revealed potential intuitive correlations between the IDH–wildtype increased heterogeneity and the texture complexity. These results strengthened our hypothesis that DSC–MRI radiogenomics in gliomas hold the potential to provide increased predictive performance from models that generalize well and provide understandable patterns between IDH mutation status and the extracted features toward enabling the clinical translation of radiogenomics in neuro-oncology. Full article

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an autoimmune entity comprised of heterogenous syndromes affecting both the peripheral and central nervous system. Research on the pathophysiological substrate of NPSLE manifestations, including functional neuroimaging studies, is extremely limited. The present study examined person-specific patterns of whole-brain functional connectivity in NPSLE patients (n = 44) and age-matched healthy control participants (n = 39). Static functional connectivity graphs were calculated comprised of connection strengths between 90 brain regions. These connections were subsequently filtered through rigorous surrogate analysis, a technique borrowed from physics, novel to neuroimaging. Next, global as well as nodal network metrics were estimated for each individual functional brain network and were input to a robust machine learning algorithm consisting of a random forest feature selection and nested cross-validation strategy. The proposed pipeline is data-driven in its entirety, and several tests were performed in order to ensure model robustness. The best-fitting model utilizing nodal graph metrics for 11 brain regions was associated with 73.5% accuracy (74.5% sensitivity and 73% specificity) in discriminating NPSLE from healthy individuals with adequate statistical power. Closer inspection of graph metric values suggested an increased role within the functional brain network in NSPLE (indicated by higher nodal degree, local efficiency, betweenness centrality, or eigenvalue efficiency) as compared to healthy controls for seven brain regions and a reduced role for four areas. These findings corroborate earlier work regarding hemodynamic disturbances in these brain regions in NPSLE. The validity of the results is further supported by significant associations of certain selected graph metrics with accumulated organ damage incurred by lupus, with visuomotor performance and mental flexibility scores obtained independently from NPSLE patients. Full article