Regulation of cervical cancer via G15-mediated inhibition of G protein-coupled estrogen receptor.

Cervical cancer is among the most common gynecological malignancies. G protein-coupled estrogen receptor (GPER) is involved in the development of various tumors; however, its role in cervical cancer remains unclear. We investigated whether G15, an inhibitor of GPER, can regulate its expression and affect cervical cancer progression. We examined the biological behaviors of G15-treated SiHa and HeLa cells using Cell Counting Kit-8, monoclonal proliferation, plate scratching, and Transwell invasion experiments. Western blotting was used to detect the expression of GPER, E-cadherin, N-cadherin, vimentin, Bcl-2, Bax, phosphatidylinositol-3-kinase (PI3K)/AKT, and programmed death ligand 1 (PD-L1). The expression of GPER, E-cadherin, vimentin, and PD-L1 in cervical cancer and adjacent tissues was detected using immunohistochemistry. The correlation between GPER expression and clinicopathological characteristics was analyzed. The expression of GPER in cervical cancer tissues was significantly higher than that in paracancerous tissues, and it was detected in the membrane and cytoplasm of SiHa and HeLa cells. The proliferation, migration, and invasion abilities of SiHa and HeLa cells were reduced after G15 treatment. The G15-treated groups exhibited higher expression of E-cadherin and Bax and lower expression of N-cadherin, vimentin, Bcl-2, GPER, p-PI3K, p-AKT, and PD-L1 than the control group. The expression of E-cadherin was lower and that of vimentin was higher in cancer tissues than in paracancerous tissues; PD-L1 was highly expressed in tumor and stromal cells in cancer tissues but not in paracancerous tissues. G15 functions by regulating the GPER/PI3K/AKT/PD-L1 signaling pathway and may serve as a new immunotherapy for treating patients with cervical cancer.

Exploring non-invasive precision treatment in non-small cell lung cancer patients through deep learning radiomics across imaging features and molecular phenotypes.

BACKGROUND: Accurate prediction of tumor molecular alterations is vital for optimizing cancer treatment. Traditional tissue-based approaches encounter limitations due to invasiveness, heterogeneity, and molecular dynamic changes. We aim to develop and validate a deep learning radiomics framework to obtain imaging features that reflect various molecular changes, aiding first-line treatment decisions for cancer patients. METHODS: We conducted a retrospective study involving 508 NSCLC patients from three institutions, incorporating CT images and clinicopathologic data. Two radiomic scores and a deep network feature were constructed on three data sources in the 3D tumor region. Using these features, we developed and validated the 'Deep-RadScore,' a deep learning radiomics model to predict prognostic factors, gene mutations, and immune molecule expression levels. FINDINGS: The Deep-RadScore exhibits strong discrimination for tumor molecular features. In the independent test cohort, it achieved impressive AUCs: 0.889 for lymphovascular invasion, 0.903 for pleural invasion, 0.894 for T staging; 0.884 for EGFR and ALK, 0.896 for KRAS and PIK3CA, 0.889 for TP53, 0.895 for ROS1; and 0.893 for PD-1/PD-L1. Fusing features yielded optimal predictive power, surpassing any single imaging feature. Correlation and interpretability analyses confirmed the effectiveness of customized deep network features in capturing additional imaging phenotypes beyond known radiomic features. INTERPRETATION: This proof-of-concept framework demonstrates that new biomarkers across imaging features and molecular phenotypes can be provided by fusing radiomic features and deep network features from multiple data sources. This holds the potential to offer valuable insights for radiological phenotyping in characterizing diverse tumor molecular alterations, thereby advancing the pursuit of non-invasive personalized treatment for NSCLC patients.

Non-invasive decision support for clinical treatment of non-small cell lung cancer using a multiscale radiomics approach.

BACKGROUND: Selecting therapeutic strategies for cancer patients is typically based on key target-molecule biomarkers that play an important role in cancer onset, progression, and prognosis. Thus, there is a pressing need for novel biomarkers that can be utilized longitudinally to guide treatment selection. METHODS: Using data from 508 non-small cell lung cancer (NSCLC) patients across three institutions, we developed and validated a comprehensive predictive biomarker that distinguishes six genotypes and infiltrative immune phenotypes. These features were analyzed to establish the association between radiological phenotypes and tumor genotypes/immune phenotypes and to create a radiological interpretation of molecular features. In addition, we assessed the sensitivity of the models by evaluating their performance at five different voxel intervals, resulting in improved generalizability of the proposed approach. FINDINGS: The radiomics model we developed, which integrates clinical factors and multi-regional features, outperformed the conventional model that only uses clinical and intratumoral features. Our combined model showed significant performance for EGFR, KRAS, ALK, TP53, PIK3CA, and ROS1 mutation status with AUCs of 0.866, 0.874, 0.902, 0.850, 0.860, and 0.900, respectively. Additionally, the predictive performance for PD-1/PD-L1 was 0.852. Although the performance of all models decreased to different degrees at five different voxel space resolutions, the performance advantage of the combined model did not change. CONCLUSIONS: We validated multiscale radiomic signatures across tumor genotypes and immunophenotypes in a multi-institutional cohort. This imaging-based biomarker offers a non-invasive approach to select patients with NSCLC who are sensitive to targeted therapies or immunotherapy, which is promising for developing personalized treatment strategies during therapy.

Radiomics under 2D regions, 3D regions, and peritumoral regions reveal tumor heterogeneity in non-small cell lung cancer: a multicenter study.

PURPOSE: Lung cancer has significant genetic and phenotypic heterogeneity, leading to poor prognosis. Radiomic features have emerged as promising predictors of the tumor phenotype. However, the role of underlying information surrounding the cancer remains unclear. MATERIALS AND METHODS: We conducted a retrospective study of 508 patients with NSCLC from three institutions. Radiomics models were built using features from six tumor regions and seven classifiers to predict three prognostically significant tumor phenotypes. The models were evaluated and interpreted by the mean area under the receiver operating characteristic curve (AUC) under nested cross-validation and Shapley values. The best-performing predictive models corresponding to six tumor regions and three tumor phenotypes were identified for further comparative analysis. In addition, we designed five experiments with different voxel spacing to assess the sensitivity of the experimental results to the spatial resolution of the voxels. RESULTS: Our results demonstrated that models based on 2D, 3D, and peritumoral region features yielded mean AUCs and 95% confidence intervals of 0.759 and [0.747-0.771] for lymphovascular invasion, 0.889 and [0.882-0.896] for pleural invasion, and 0.839 and [0.829-0.849] for T-staging in the testing cohort, which was significantly higher than all other models. Similar results were obtained for the model combining the three regional features at five voxel spacings. CONCLUSION: Our study revealed the predictive role of the developed methods with multi-regional features for the preoperative assessment of prognostic factors in NSCLC. The analysis of different voxel spacing and model interpretability strengthens the experimental findings and contributes to understanding the biological significance of the radiological phenotype.

Focal Boundary Dice: Improved Breast Tumor Segmentation from MRI Scan.

Focal Boundary Dice, a new segmentation evaluation measure, was hereby presented, with the focus on boundary quality and class imbalance. Extensive analysis was carried out across different error types with varied object sizes of imaged tumors from Magnetic Resonance Imaging (MRI) scans, and the results show that Focal Boundary Dice is significantly more adaptive than the standard Focal and Dice measures to boundary errors for imaged tumors from MRI scans and does not over-penalize errors on the division of the boundary, including smaller imaged objects. Based on Boundary Dice, the standard evaluation protocols for tumor segmentation tasks were updated by proposing the Focal Boundary Dice. The contradiction between the target and the background area, and the conflict between the importance and the attention of boundary features were mainly solved. Meanwhile, a boundary attention module was introduced to further extract the tumor edge features. The new quality measure presents several desirable characteristics, including higher accuracy in the selection of hard samples, prediction/ground-truth pairs, and balanced responsiveness with across scales, which jointly make it more suitable for segmentation evaluation than other classification-focused measures such as combined Intersection-over-Union and Boundary binary cross-entropy loss, Boundary binary cross-entropy loss and Shape-aware Loss. The experiments show that the new evaluation metrics allow boundary quality improvements and image segmentation accuracy that are generally overlooked by current Dice-based evaluation metrics and deep learning models. It is expected that the adoption of the new boundary-adaptive evaluation metrics will facilitate the rapid progress in segmentation methods, and further contribute to the improvement of classification accuracy.

Prospective clinical research of radiomics and deep learning in oncology: A translational review.

Radiomics and deep learning (DL) hold transformative promise and substantial and significant advances in oncology; however, most methods have been tested in retrospective or simulated settings. There is considerable interest in the biomarker validation, clinical utility, and methodological robustness of these studies and their deployment in real-world settings. This review summarizes the characteristics of studies, the level of prospective validation, and the overview of research on different clinical endpoints. The discussion of methodological robustness shows the potential for independent external replication of prospectively reported results. These in-depth analyses further describe the barriers limiting the translation of radiomics and DL into primary care options and provide specific recommendations regarding clinical deployment. Finally, we propose solutions for integrating novel approaches into the treatment environment to unravel the critical process of translating AI models into the clinical routine and explore strategies to improve personalized medicine.

MRI Radiogenomics in Precision Oncology: New Diagnosis and Treatment Method.

Precision medicine for cancer affords a new way for the most accurate and effective treatment to each individual cancer. Given the high time-evolving intertumor and intratumor heterogeneity features of personal medicine, there are still several obstacles hindering its diagnosis and treatment in clinical practice regardless of extensive exploration on it over the past years. This paper is to investigate radiogenomics methods in the literature for precision medicine for cancer focusing on the heterogeneity analysis of tumors. Based on integrative analysis of multimodal (parametric) imaging and molecular data in bulk tumors, a comprehensive analysis and discussion involving the characterization of tumor heterogeneity in imaging and molecular expression are conducted. These investigations are intended to (i) fully excavate the multidimensional spatial, temporal, and semantic related information regarding high-dimensional breast magnetic resonance imaging data, with integration of the highly specific structured data of genomics and combination of the diagnosis and cognitive process of doctors, and (ii) establish a radiogenomics data representation model based on multidimensional consistency analysis with multilevel spatial-temporal correlations.

Deep Learning With Radiomics for Disease Diagnosis and Treatment: Challenges and Potential.

The high-throughput extraction of quantitative imaging features from medical images for the purpose of radiomic analysis, i.e., radiomics in a broad sense, is a rapidly developing and emerging research field that has been attracting increasing interest, particularly in multimodality and multi-omics studies. In this context, the quantitative analysis of multidimensional data plays an essential role in assessing the spatio-temporal characteristics of different tissues and organs and their microenvironment. Herein, recent developments in this method, including manually defined features, data acquisition and preprocessing, lesion segmentation, feature extraction, feature selection and dimension reduction, statistical analysis, and model construction, are reviewed. In addition, deep learning-based techniques for automatic segmentation and radiomic analysis are being analyzed to address limitations such as rigorous workflow, manual/semi-automatic lesion annotation, and inadequate feature criteria, and multicenter validation. Furthermore, a summary of the current state-of-the-art applications of this technology in disease diagnosis, treatment response, and prognosis prediction from the perspective of radiology images, multimodality images, histopathology images, and three-dimensional dose distribution data, particularly in oncology, is presented. The potential and value of radiomics in diagnostic and therapeutic strategies are also further analyzed, and for the first time, the advances and challenges associated with dosiomics in radiotherapy are summarized, highlighting the latest progress in radiomics. Finally, a robust framework for radiomic analysis is presented and challenges and recommendations for future development are discussed, including but not limited to the factors that affect model stability (medical big data and multitype data and expert knowledge in medical), limitations of data-driven processes (reproducibility and interpretability of studies, different treatment alternatives for various institutions, and prospective researches and clinical trials), and thoughts on future directions (the capability to achieve clinical applications and open platform for radiomics analysis).

Circulating T-Cell Repertoires Correlate With the Tumor Response in Patients With Breast Cancer Receiving Neoadjuvant Chemotherapy.

PURPOSE: Neoadjuvant chemotherapy (NAC) has been widely used in patients with breast cancer to minish tumor burden and increase resection rate of cancer. T-cell repertoire has been believed to be able to monitor antitumor immune responses. This study aimed to explore the dynamic change of T-cell repertoire and its clinical value in evaluating the tumor response in patients with breast cancer receiving NAC. MATERIALS AND METHODS: Ninety-four patients who underwent NAC before surgery were recruited, and peripheral blood samples were collected at multiple time points during NAC. High-throughput T-cell receptor (TCR)-ß sequencing was used to characterize the T-cell repertoire of every sample and analyzed the changes in circulating T-cell repertoire during NAC. RESULTS: We found that the diversity of TCR repertoires was associated with age and clinical stage of the patients with breast cancer. The distribution of Vß and Jß genes in TCR repertoires was skewed in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. Vß20.1 and Vß30 expression levels before NAC correlate with tumor response after all cycles of NAC in HER2- and HER2+ patients, respectively. Some CDR3 motifs that correlated with clinical response in either HER2+ or HER2- patients were identified. Besides, TCR repertoire evolved during NAC and the diversity of TCR repertoire decreased more after two cycles of NAC in patients with good tumor response after all cycles of NAC (P = .0061). CONCLUSION: Our results demonstrated that TCR repertoire correlated with the characteristics of the tumor, such as the expression status of HER2. Moreover, some characteristics of TCR repertoires that correlated with clinical response were identified and they might provide useful information to tailor therapeutic regimens at the early cycle of NAC.

MRI radiogenomics for intelligent diagnosis of breast tumors and accurate prediction of neoadjuvant chemotherapy responses-a review.

BACKGROUND AND OBJECTIVE: This paper aims to overview multidimensional mining algorithms in relation to Magnetic Resonance Imaging (MRI) radiogenomics for computer aided detection and diagnosis of breast tumours. The work also aims to address a new problem in radiogenomics mining: how to combine structural radiomics information with non-structural genomics information for improving the accuracy and efficacy of Neoadjuvant Chemotherapy (NAC). METHODS: This requires the automated extraction of parameters from non-structural breast radiomics data, and finding feature vectors with diagnostic value, which then are combined with genomics data. In order to address the problem of weakly labelled tumour images, a Generative Adiversarial Networks (GAN) based deep learning strategy is proposed for the classification of tumour types; this has significant potential for providing accurate real-time identification of tumorous regions from MRI scans. In order to efficiently integrate in a deep learning framework different features from radiogenomics datasets at multiple spatio-temporal resolutions, pyramid structured and multi-scale densely connected U-Nets are proposed. A bidirectional gated recurrent unit (BiGRU) combined with an attention based deep learning approach is also proposed. RESULTS: The aim is to accurately predict NAC responses by combining imaging and genomic datasets. The approaches discussed incorporate some of the latest developments in of current signal processing and artificial intelligence and have significant potential in advancing and provide a development platform for future cutting-edge biomedical radiogenomics analysis. CONCLUSIONS: The association of genotypic and phenotypic features is at the core of the emergent field of Precision Medicine. It makes use of advances in biomedical big data analysis, which enables the correlation between disease-associated phenotypic characteristics, genetics polymorphism and gene activation to be revealed.

Automatic breast tissue segmentation in MRIs with morphology snake and deep denoiser training via extended Stein's unbiased risk estimator.

Accurate segmentation of the breast tissue is a significant challenge in the analysis of breast MR images, especially analysis of breast images with low contrast. Most of the existing methods for breast segmentation are semi-automatic and limited in their ability to achieve accurate results. This is because of difficulties in removing landmarks from noisy magnetic resonance images (MRI). Especially, when tumour is imaged for scanning, how to isolate the tumour region from chest will directly affect the accuracy for tumour to be detected. Due to low intensity levels and the close connection between breast and chest portion in MRIs, this study proposes an innovative, fully automatic and fast segmentation approach which combines histogram with inverse Gaussian gradient for morphology snakes, along with extended Stein's unbiased risk estimator (eSURE) applied for unsupervised learning of deep neural network Gaussian denoisers, aimed at accurate identification of landmarks such as chest and breast.

Artificial Intelligence in Breast MRI Radiogenomics: Towards Accurate Prediction of Neoadjuvant Chemotherapy Responses.

Neoadjuvant Chemotherapy (NAC) in breast cancer patients has considerable prognostic and treatment potential and can be tailored to individual patients as part of precision medicine protocols. This work reviews recent advances in artificial intelligence so as to enable the use of radiogenomics for accurate NAC analysis and prediction. The work addresses a new problem in radiogenomics mining: How to combine structural radiomics information and non-structural genomics information for accurate NAC prediction. This requires the automated extraction of parameters from structural breast radiomics data, and finding non-structural feature vectors with diagnostic value, which then are combined with genomics data acquired from exocrine bodies in blood samples from a cohort of cancer patients to enable accurate NAC prediction. A self-attention-based deep learning approach, along with an effective multi-channel tumour image reconstruction algorithm of high dimensionality, is proposed. The aim was to generate non-structural feature vectors for accurate prediction of the NAC responses by combining imaging datasets with exocrine body related genomics analysis.

Pattern identification of biomedical images with time series: Contrasting THz pulse imaging with DCE-MRIs.

OBJECTIVE: We provide a survey of recent advances in biomedical image analysis and classification from emergent imaging modalities such as terahertz (THz) pulse imaging (TPI) and dynamic contrast-enhanced magnetic resonance images (DCE-MRIs) and identification of their underlining commonalities. METHODS: Both time and frequency domain signal pre-processing techniques are considered: noise removal, spectral analysis, principal component analysis (PCA) and wavelet transforms. Feature extraction and classification methods based on feature vectors using the above processing techniques are reviewed. A tensorial signal processing de-noising framework suitable for spatiotemporal association between features in MRI is also discussed. VALIDATION: Examples where the proposed methodologies have been successful in classifying TPIs and DCE-MRIs are discussed. RESULTS: Identifying commonalities in the structure of such heterogeneous datasets potentially leads to a unified multi-channel signal processing framework for biomedical image analysis. CONCLUSION: The proposed complex valued classification methodology enables fusion of entire datasets from a sequence of spatial images taken at different time stamps; this is of interest from the viewpoint of inferring disease proliferation. The approach is also of interest for other emergent multi-channel biomedical imaging modalities and of relevance across the biomedical signal processing community.