Incidence rate of occult lymph node metastasis in clinical T1-2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study : Original research.

BACKGROUND: This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. METHODS: By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 - 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). RESULTS: The initial investigation revealed a 33.9% OLM positivity rate in cT1 - 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 - 2N0M0 SCLC patients. CONCLUSIONS: The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 - 2N0M0 SCLC.

Spatial distance between tumor and lymphocyte can predict the survival of patients with resectable lung adenocarcinoma.

Background and objective: Spatial interaction between tumor-infiltrating lymphocytes (TILs) and tumor cells is valuable in predicting the effectiveness of immune response and prognosis amongst patients with lung adenocarcinoma (LUAD). Recent evidence suggests that the spatial distance between tumor cells and lymphocytes also influences the immune responses, but the distance analysis based on Hematoxylin and Eosin (H&E) -stained whole-slide images (WSIs) remains insufficient. To address this issue, we aim to explore the relationship between distance and prognosis prediction of patients with LUAD in this study. Methods: We recruited patients with resectable LUAD from three independent cohorts in this multi-center study. We proposed a simple but effective deep learning-driven workflow to automatically segment different cell types in the tumor region using the HoVer-Net model, and quantified the spatial distance (DIST) between tumor cells and lymphocytes based on H&E-stained WSIs. The association of DIST with disease-free survival (DFS) was explored in the discovery set (D1, n = 276) and the two validation sets (V1, n = 139; V2, n = 115). Results: In multivariable analysis, the low DIST group was associated with significantly better DFS in the discovery set (D1, HR, 0.61; 95 % CI, 0.40-0.94; p = 0.027) and the two validation sets (V1, HR, 0.54; 95 % CI, 0.32-0.91; p = 0.022; V2, HR, 0.44; 95 % CI, 0.24-0.81; p = 0.009). By integrating the DIST with clinicopathological factors, the integrated model (full model) had better discrimination for DFS in the discovery set (C-index, D1, 0.745 vs. 0.723) and the two validation sets (V1, 0.621 vs. 0.596; V2, 0.671 vs. 0.650). Furthermore, the computerized DIST was associated with immune phenotypes such as immune-desert and inflamed phenotypes. Conclusions: The integration of DIST with clinicopathological factors could improve the stratification performance of patients with resectable LUAD, was beneficial for the prognosis prediction of LUAD patients, and was also expected to assist physicians in individualized treatment.

Imaging segmentation mechanism for rectal tumors using improved U-Net.

OBJECTIVE: In radiation therapy, cancerous region segmentation in magnetic resonance images (MRI) is a critical step. For rectal cancer, the automatic segmentation of rectal tumors from an MRI is a great challenge. There are two main shortcomings in existing deep learning-based methods that lead to incorrect segmentation: 1) there are many organs surrounding the rectum, and the shape of some organs is similar to that of rectal tumors; 2) high-level features extracted by conventional neural networks often do not contain enough high-resolution information. Therefore, an improved U-Net segmentation network based on attention mechanisms is proposed to replace the traditional U-Net network. METHODS: The overall framework of the proposed method is based on traditional U-Net. A ResNeSt module was added to extract the overall features, and a shape module was added after the encoder layer. We then combined the outputs of the shape module and the decoder to obtain the results. Moreover, the model used different types of attention mechanisms, so that the network learned information to improve segmentation accuracy. RESULTS: We validated the effectiveness of the proposed method using 3773 2D MRI datasets from 304 patients. The results showed that the proposed method achieved 0.987, 0.946, 0.897, and 0.899 for Dice, MPA, MioU, and FWIoU, respectively; these values are significantly better than those of other existing methods. CONCLUSION: Due to time savings, the proposed method can help radiologists segment rectal tumors effectively and enable them to focus on patients whose cancerous regions are difficult for the network to segment. SIGNIFICANCE: The proposed method can help doctors segment rectal tumors, thereby ensuring good diagnostic quality and accuracy.

FedDUS: Lung tumor segmentation on CT images through federated semi-supervised with dynamic update strategy.

BACKGROUND AND OBJECTIVE: Lung tumor annotation is a key upstream task for further diagnosis and prognosis. Although deep learning techniques have promoted automation of lung tumor segmentation, there remain challenges impeding its application in clinical practice, such as a lack of prior annotation for model training and data-sharing among centers. METHODS: In this paper, we use data from six centers to design a novel federated semi-supervised learning (FSSL) framework with dynamic model aggregation and improve segmentation performance for lung tumors. To be specific, we propose a dynamically updated algorithm to deal with model parameter aggregation in FSSL, which takes advantage of both the quality and quantity of client data. Moreover, to increase the accessibility of data in the federated learning (FL) network, we explore the FAIR data principle while the previous federated methods never involve. RESULT: The experimental results show that the segmentation performance of our model in six centers is 0.9348, 0.8436, 0.8328, 0.7776, 0.8870 and 0.8460 respectively, which is superior to traditional deep learning methods and recent federated semi-supervised learning methods. CONCLUSION: The experimental results demonstrate that our method is superior to the existing FSSL methods. In addition, our proposed dynamic update strategy effectively utilizes the quality and quantity information of client data and shows efficiency in lung tumor segmentation. The source code is released on (https://github.com/GDPHMediaLab/FedDUS).

A medical image segmentation method for rectal tumors based on multi-scale feature retention and multiple attention mechanisms.

BACKGROUND: With the continuous development of deep learning algorithms in the field of medical images, models for medical image processing based on convolutional neural networks have made great progress. Since medical images of rectal tumors are characterized by specific morphological features and complex edges that differ from natural images, achieving good segmentation results often requires a higher level of enrichment through the utilization of semantic features. PURPOSE: The efficiency of feature extraction and utilization has been improved to some extent through enhanced hardware arithmetic and deeper networks in most models. However, problems still exist with detail loss and difficulty in feature extraction, arising from the extraction of high-level semantic features in deep networks. METHODS: In this work, a novel medical image segmentation model has been proposed for Magnetic Resonance Imaging (MRI) image segmentation of rectal tumors. The model constructs a backbone architecture based on the idea of jump-connected feature fusion and solves the problems of detail feature loss and low segmentation accuracy using three novel modules: Multi-scale Feature Retention (MFR), Multi-branch Cross-channel Attention (MCA), and Coordinate Attention (CA). RESULTS: Compared with existing methods, our proposed model is able to segment the tumor region more effectively, achieving 97.4% and 94.9% in Dice and mIoU metrics, respectively, exhibiting excellent segmentation performance and computational speed. CONCLUSIONS: Our proposed model has improved the accuracy of both lesion region and tumor edge segmentation. In particular, the determination of the lesion region can help doctors identify the tumor location in clinical diagnosis, and the accurate segmentation of the tumor edge can assist doctors in judging the necessity and feasibility of surgery.

Multicenter Evaluation of a Weakly Supervised Deep Learning Model for Lymph Node Diagnosis in Rectal Cancer at MRI.

Purpose To develop a Weakly supervISed model DevelOpment fraMework (WISDOM) model to construct a lymph node (LN) diagnosis model for patients with rectal cancer (RC) that uses preoperative MRI data coupled with postoperative patient-level pathologic information. Materials and Methods In this retrospective study, the WISDOM model was built using MRI (T2-weighted and diffusion-weighted imaging) and patient-level pathologic information (the number of postoperatively confirmed metastatic LNs and resected LNs) based on the data of patients with RC between January 2016 and November 2017. The incremental value of the model in assisting radiologists was investigated. The performances in binary and ternary N staging were evaluated using area under the receiver operating characteristic curve (AUC) and the concordance index (C index), respectively. Results A total of 1014 patients (median age, 62 years; IQR, 54-68 years; 590 male) were analyzed, including the training cohort (n = 589) and internal test cohort (n = 146) from center 1 and two external test cohorts (cohort 1: 117; cohort 2: 162) from centers 2 and 3. The WISDOM model yielded an overall AUC of 0.81 and C index of 0.765, significantly outperforming junior radiologists (AUC = 0.69, P < .001; C index = 0.689, P < .001) and performing comparably with senior radiologists (AUC = 0.79, P = .21; C index = 0.788, P = .22). Moreover, the model significantly improved the performance of junior radiologists (AUC = 0.80, P < .001; C index = 0.798, P < .001) and senior radiologists (AUC = 0.88, P < .001; C index = 0.869, P < .001). Conclusion This study demonstrates the potential of WISDOM as a useful LN diagnosis method using routine rectal MRI data. The improved radiologist performance observed with model assistance highlights the potential clinical utility of WISDOM in practice. Keywords: MR Imaging, Abdomen/GI, Rectum, Computer Applications-Detection/Diagnosis Supplemental material is available for this article. Published under a CC BY 4.0 license.

A computed tomography-based multitask deep learning model for predicting tumour stroma ratio and treatment outcomes in patients with colorectal cancer: a multicentre cohort study.

BACKGROUND: Tumour-stroma interactions, as indicated by tumour-stroma ratio (TSR), offer valuable prognostic stratification information. Current histological assessment of TSR is limited by tissue accessibility and spatial heterogeneity. The authors aimed to develop a multitask deep learning (MDL) model to noninvasively predict TSR and prognosis in colorectal cancer (CRC). MATERIALS AND METHODS: In this retrospective study including 2268 patients with resected CRC recruited from four centres, the authors developed an MDL model using preoperative computed tomography (CT) images for the simultaneous prediction of TSR and overall survival. Patients in the training cohort ( n =956) and internal validation cohort (IVC, n =240) were randomly selected from centre I. Patients in the external validation cohort 1 (EVC1, n =509), EVC2 ( n =203), and EVC3 ( n =360) were recruited from other three centres. Model performance was evaluated with respect to discrimination and calibration. Furthermore, the authors evaluated whether the model could predict the benefit from adjuvant chemotherapy. RESULTS: The MDL model demonstrated strong TSR discrimination, yielding areas under the receiver operating curves (AUCs) of 0.855 (95% CI, 0.800-0.910), 0.838 (95% CI, 0.802-0.874), and 0.857 (95% CI, 0.804-0.909) in the three validation cohorts, respectively. The MDL model was also able to predict overall survival and disease-free survival across all cohorts. In multivariable Cox analysis, the MDL score (MDLS) remained an independent prognostic factor after adjusting for clinicopathological variables (all P <0.05). For stage II and stage III disease, patients with a high MDLS benefited from adjuvant chemotherapy [hazard ratio (HR) 0.391 (95% CI, 0.230-0.666), P =0.0003; HR=0.467 (95% CI, 0.331-0.659), P <0.0001, respectively], whereas those with a low MDLS did not. CONCLUSION: The multitask DL model based on preoperative CT images effectively predicted TSR status and survival in CRC patients, offering valuable guidance for personalized treatment. Prospective studies are needed to confirm its potential to select patients who might benefit from chemotherapy.

Radiomics analysis of multiparametric MRI for preoperative prediction of microsatellite instability status in endometrial cancer: a dual-center study.

Objective: To develop and validate a multiparametric MRI-based radiomics model for prediction of microsatellite instability (MSI) status in patients with endometrial cancer (EC). Methods: A total of 225 patients from Center I including 158 in the training cohort and 67 in the internal testing cohort, and 132 patients from Center II were included as an external validation cohort. All the patients were pathologically confirmed EC who underwent pelvic MRI before treatment. The MSI status was confirmed by immunohistochemistry (IHC) staining. A total of 4245 features were extracted from T2-weighted imaging (T2WI), contrast enhanced T1-weighted imaging (CE-T1WI) and apparent diffusion coefficient (ADC) maps for each patient. Four feature selection steps were used, and then five machine learning models, including Logistic Regression (LR), k-Nearest Neighbors (KNN), Naive Bayes (NB), Support Vector Machine (SVM), and Random Forest (RF), were built for MSI status prediction in the training cohort. Receiver operating characteristics (ROC) curve and decision curve analysis (DCA) were used to evaluate the performance of these models. Results: The SVM model showed the best performance with an AUC of 0.905 (95%CI, 0.848-0.961) in the training cohort, and was subsequently validated in the internal testing cohort and external validation cohort, with the corresponding AUCs of 0.875 (95%CI, 0.762-0.988) and 0.862 (95%CI, 0.781-0.942), respectively. The DCA curve demonstrated favorable clinical utility. Conclusion: We developed and validated a multiparametric MRI-based radiomics model with gratifying performance in predicting MSI status, and could potentially be used to facilitate the decision-making on clinical treatment options in patients with EC.

SwinHR: Hemodynamic-powered hierarchical vision transformer for breast tumor segmentation.

Accurate and automated segmentation of breast tumors in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) plays a critical role in computer-aided diagnosis and treatment of breast cancer. However, this task is challenging, due to random variation in tumor sizes, shapes, appearances, and blurred boundaries of tumors caused by inherent heterogeneity of breast cancer. Moreover, the presence of ill-posed artifacts in DCE-MRI further complicate the process of tumor region annotation. To address the challenges above, we propose a scheme (named SwinHR) integrating prior DCE-MRI knowledge and temporal-spatial information of breast tumors. The prior DCE-MRI knowledge refers to hemodynamic information extracted from multiple DCE-MRI phases, which can provide pharmacokinetics information to describe metabolic changes of the tumor cells over the scanning time. The Swin Transformer with hierarchical re-parameterization large kernel architecture (H-RLK) can capture long-range dependencies within DCE-MRI while maintaining computational efficiency by a shifted window-based self-attention mechanism. The use of H-RLK can extract high-level features with a wider receptive field, which can make the model capture contextual information at different levels of abstraction. Extensive experiments are conducted in large-scale datasets to validate the effectiveness of our proposed SwinHR scheme, demonstrating its superiority over recent state-of-the-art segmentation methods. Also, a subgroup analysis split by MRI scanners, field strength, and tumor size is conducted to verify its generalization. The source code is released on (https://github.com/GDPHMediaLab/SwinHR).

RTAU-Net: A novel 3D rectal tumor segmentation model based on dual path fusion and attentional guidance.

BACKGROUND AND OBJECTIVE: According to the Global Cancer Statistics 2020, colorectal cancer has the third-highest diagnosis rate (10.0 %) and the second-highest mortality rate (9.4 %) among the 36 types. Rectal cancer accounts for a large proportion of colorectal cancer. The size and shape of the rectal tumor can directly affect the diagnosis and treatment by doctors. The existing rectal tumor segmentation methods are based on two-dimensional slices, which cannot analyze a patient's tumor as a whole and lose the correlation between slices of MRI image, so the practical application value is not high. METHODS: In this paper, a three-dimensional rectal tumor segmentation model is proposed. Firstly, image preprocessing is performed to reduce the effect caused by the unbalanced proportion of background region and target region, and improve the quality of the image. Secondly, a dual-path fusion network is designed to extract both global features and local detail features of rectal tumors. The network includes two encoders, a residual encoder for enhancing the spatial detail information and feature representation of the tumor and a transformer encoder for extracting global contour information of the tumor. In the decoding stage, we merge the information extracted from the dual paths and decode them. In addition, for the problem of the complex morphology and different sizes of rectal tumors, a multi-scale fusion channel attention mechanism is designed, which can capture important contextual information of different scales. Finally, visualize the 3D rectal tumor segmentation results. RESULTS: The RTAU-Net is evaluated on the data set provided by Shanxi Provincial Cancer Hospital and Xinhua Hospital. The experimental results showed that the Dice of tumor segmentation reached 0.7978 and 0.6792, respectively, which improved by 2.78 % and 7.02 % compared with suboptimal model. CONCLUSIONS: Although the morphology of rectal tumors varies, RTAU-Net can precisely localize rectal tumors and learn the contour and details of tumors, which can relieve physicians' workload and improve diagnostic accuracy.

RACK1 facilitates breast cancer progression by competitively inhibiting the binding of ß-catenin to PSMD2 and enhancing the stability of ß-catenin.

The receptor for activated C kinase 1 (RACK1) is a key scaffolding protein with multifunctional and multifaceted properties. By mediating protein-protein interactions, RACK1 integrates multiple intracellular signals involved in the regulation of various physiological and pathological processes. Dysregulation of RACK1 has been implicated in the initiation and progression of many tumors. However, the exact function of RACK1 in cancer cellular processes, especially in proliferation, remains controversial. Here, we show that RACK1 is required for breast cancer cell proliferation in vitro and tumor growth in vivo. This effect of RACK1 is associated with its ability to enhance ß-catenin stability and activate the canonical WNT signaling pathway in breast cancer cells. We identified PSMD2, a key component of the proteasome, as a novel binding partner for RACK1 and ß-catenin. Interestingly, although there is no interaction between RACK1 and ß-catenin, RACK1 binds PSMD2 competitively with ß-catenin. Moreover, RACK1 prevents ubiquitinated ß-catenin from binding to PSMD2, thereby protecting ß-catenin from proteasomal degradation. Collectively, our findings uncover a novel mechanism by which RACK1 increases ß-catenin stability and promotes breast cancer proliferation.

Multisequence MRI-based radiomics model for predicting POLE mutation status in patients with endometrial cancer.

OBJECTIVES: Preoperative identification of POLE mutation status would help tailor the surgical procedure and adjuvant treatment strategy. This study aimed to explore the feasibility of developing a radiomics model to pre-operatively predict the pathogenic POLE mutation status in patients with EC. METHODS: The retrospective study involved 138 patients with histopathologically confirmed EC (35 POLE-mutant vs 103 non-POLE-mutant). After selecting relevant features with a series of steps, three radiomics signatures were built based on axial fat-saturation T2WI, DWI, and CE-T1WI images, respectively. Then, two radiomics models which integrated features from T2WI + DWI and T2WI + DWI+CE-T1WI were further developed using multivariate logistic regression. The performance of the radiomics model was evaluated from discrimination, calibration, and clinical utility aspects. RESULTS: Among all the models, radiomics model2 (RM2), which integrated features from all three sequences, showed the best performance, with AUCs of 0.885 (95%CI: 0.828-0.942) and 0.810 (95%CI: 0.653-0.967) in the training and validation cohorts, respectively. The net reclassification index (NRI) and integrated discrimination improvement (IDI) analyses indicated that RM2 had improvement in predicting POLE mutation status when compared with the single-sequence-based signatures and the radiomics model1 (RM1). The calibration curve, decision curve analysis, and clinical impact curve suggested favourable calibration and clinical utility of RM2. CONCLUSIONS: The RM2, fusing features from three sequences, could be a potential tool for the non-invasive preoperative identification of patients with POLE-mutant EC, which is helpful for developing individualized therapeutic strategies. ADVANCES IN KNOWLEDGE: This study developed a potential surrogate of POLE sequencing, which is cost-efficient and non-invasive.

Fructose-Induced mTORC1 Activation Promotes Pancreatic Cancer Progression through Inhibition of Autophagy.

Excessive fructose intake is associated with the occurrence, progression, and poor prognosis of various tumors. A better understanding of the mechanisms underlying the functions of fructose in cancer could facilitate the development of better treatment and prevention strategies. In this study, we investigated the functional association between fructose utilization and pancreatic ductal adenocarcinoma (PDAC) progression. Fructose could be taken up and metabolized by PDAC cells and provided an adaptive survival mechanism for PDAC cells under glucose-deficient conditions. GLUT5-mediated fructose metabolism maintained the survival, proliferation, and invasion capacities of PDAC cells in vivo and in vitro. Fructose metabolism not only provided ATP and biomass to PDAC cells but also conferred metabolic plasticity to the cells, making them more adaptable to the tumor microenvironment. Mechanistically, fructose activated the AMP-activated protein kinase (AMPK)-mTORC1 signaling pathway to inhibit glucose deficiency-induced autophagic cell death. Moreover, the fructose-specific transporter GLUT5 was highly expressed in PDAC tissues and was an independent marker of disease progression in patients with PDAC. These findings provide mechanistic insights into the role of fructose in promoting PDAC progression and offer potential strategies for targeting metabolism to treat PDAC. SIGNIFICANCE: Fructose activates AMPK-mTORC1 signaling to inhibit autophagy-mediated cell death in pancreatic cancer cells caused by glucose deficiency, facilitating metabolic adaptation to the tumor microenvironment and supporting tumor growth.

Computerized tertiary lymphoid structures density on H&E-images is a prognostic biomarker in resectable lung adenocarcinoma.

The increased amount of tertiary lymphoid structures (TLSs) is associated with a favorable prognosis in patients with lung adenocarcinoma (LUAD). However, evaluating TLSs manually is an experience-dependent and time-consuming process, which limits its clinical application. In this multi-center study, we developed an automated computational workflow for quantifying the TLS density in the tumor region of routine hematoxylin and eosin (H&E)-stained whole-slide images (WSIs). The association between the computerized TLS density and disease-free survival (DFS) was further explored in 802 patients with resectable LUAD of three cohorts. Additionally, a Cox proportional hazard regression model, incorporating clinicopathological variables and the TLS density, was established to assess its prognostic ability. The computerized TLS density was an independent prognostic biomarker in patients with resectable LUAD. The integration of the TLS density with clinicopathological variables could support individualized clinical decision-making by improving prognostic stratification.

An MRI-based scoring system for pretreatment risk stratification in locally advanced rectal cancer.

BACKGROUND: Accurately assessing the risk of recurrence in patients with locally advanced rectal cancer (LARC) before treatment is important for the development of treatment strategies. The purpose of this study is to develop an MRI-based scoring system to predict the risk of recurrence in patients with LARC. METHODS: This was a multicenter observational study that enrolled participants who underwent neoadjuvant chemoradiotherapy. To evaluate the risk of recurrence in these patients, we developed the mrDEC scoring system and assessed inter-reader agreement. Additionally, we plotted Kaplan-Meier curves to compare the 3-year disease-free survival (DFS) and 5-year overall survival (OS) rates among patients with different mrDEC scores. RESULTS: A total of 1287 patients with LARC were included in this study. We observed substantial inter-reader agreement for mrDEC. Based on the mrDEC scores ranging from 0 to 3, the patients were categorized into four groups. The 3-year DFS rates for the groups were 91.0%, 79.5%, 65.5%, and 44.0% (P < 0.0001), respectively, and the 5-year OS rates were 92.9%, 87.1%, 74.8%, and 44.5%, respectively (P < 0.0001). CONCLUSIONS: The mrDEC scoring system proved to be an effective tool for predicting the prognosis of patients with LARC and can assist clinicians in clinical decision-making.

Comprehensively analysis of splicing factors to construct prognosis prediction classifier in prostate cancer.

Splicing factors (SFs) are proteins that control the alternative splicing (AS) of RNAs, which have been recognized as new cancer hallmarks. Their dysregulation has been found to be involved in many biological processes of cancer, such as carcinogenesis, proliferation, metastasis and senescence. Dysregulation of SFs has been demonstrated to contribute to the progression of prostate cancer (PCa). However, a comprehensive analysis of the prognosis value of SFs in PCa is limited. In this work, we systematically analysed 393 SFs to deeply characterize the expression patterns, clinical relevance and biological functions of SFs in PCa. We identified 53 survival-related SFs that can stratify PCa into two de nove molecular subtypes with distinct mRNA expression and AS-event expression patterns and displayed significant differences in pathway activity and clinical outcomes. An SF-based classifier was established using LASSO-COX regression with six key SFs (BCAS1, LSM3, DHX16, NOVA2, RBM47 and SNRPN), which showed promising prognosis-prediction performance with a receiver operating characteristic (ROC) >0.700 in both the training and testing datasets, as well as in three external PCa cohorts (DKFZ, GSE70769 and GSE21035). CRISPR/CAS9 screening data and cell-level functional analysis suggested that LSM3 and DHX16 are essential factors for the proliferation and cell cycle progression in PCa cells. This study proposes that SFs and AS events are potential multidimensional biomarkers for the diagnosis, prognosis and treatment of PCa.

Fructose promotes angiogenesis by improving vascular endothelial cell function and upregulating VEGF expression in cancer cells.

BACKGROUND: Fructose is a very common sugar found in natural foods, while current studies demonstrate that high fructose intake is significantly associated with increased risk of multiple cancers and more aggressive tumor behavior, but the relevant mechanisms are not fully understood. METHODS: Tumor-grafting experiments and in vitro angiogenesis assays were conducted to detect the effect of fructose and the conditioned medium of fructose-cultured tumor cells on biological function of vascular endothelial cells (VECs) and angiogenesis. 448 colorectal cancer specimens were utilized to analyze the relationship between Glut5 expression levels in VECs and tumor cells and microvascular density (MVD). RESULTS: We found that fructose can be metabolized by VECs and activate the Akt and Src signaling pathways, thereby enhancing the proliferation, migration, and tube-forming abilities of VECs and thereby promoting angiogenesis. Moreover, fructose can also improve the expression of vascular endothelial growth factor (VEGF) by upregulating the production of reactive oxygen species (ROS) in colorectal cancer cells, thus indirectly enhancing the biological function of VECs. Furthermore, this pro-angiogenic effect of fructose metabolism has also been well validated in clinical colorectal cancer tissues and mouse models. Fructose contributes to angiogenesis in mouse subcutaneous tumor grafts, and MVD is positively correlated with Glut5 expression levels of both endothelial cells and tumor cells of human colorectal cancer specimens. CONCLUSIONS: These findings establish the direct role and mechanism by which fructose promotes tumor progression through increased angiogenesis, and provide reliable evidence for a better understanding of tumor metabolic reprogramming.

MRI-based Quantification of Intratumoral Heterogeneity for Predicting Treatment Response to Neoadjuvant Chemotherapy in Breast Cancer.

Background Breast cancer is highly heterogeneous, resulting in different treatment responses to neoadjuvant chemotherapy (NAC) among patients. A noninvasive quantitative measure of intratumoral heterogeneity (ITH) may be valuable for predicting treatment response. Purpose To develop a quantitative measure of ITH on pretreatment MRI scans and test its performance for predicting pathologic complete response (pCR) after NAC in patients with breast cancer. Materials and Methods Pretreatment MRI scans were retrospectively acquired in patients with breast cancer who received NAC followed by surgery at multiple centers from January 2000 to September 2020. Conventional radiomics (hereafter, C-radiomics) and intratumoral ecological diversity features were extracted from the MRI scans, and output probabilities of imaging-based decision tree models were used to generate a C-radiomics score and ITH index. Multivariable logistic regression analysis was used to identify variables associated with pCR, and significant variables, including clinicopathologic variables, C-radiomics score, and ITH index, were combined into a predictive model for which performance was assessed using the area under the receiver operating characteristic curve (AUC). Results The training data set was comprised of 335 patients (median age, 48 years [IQR, 42-54 years]) from centers A and B, and 590, 280, and 384 patients (median age, 48 years [IQR, 41-55 years]) were included in the three external test data sets. Molecular subtype (odds ratio [OR] range, 4.76-8.39 [95% CI: 1.79, 24.21]; all P < .01), ITH index (OR, 30.05 [95% CI: 8.43, 122.64]; P < .001), and C-radiomics score (OR, 29.90 [95% CI: 12.04, 81.70]; P < .001) were independently associated with the odds of achieving pCR. The combined model showed good performance for predicting pCR to NAC in the training data set (AUC, 0.90) and external test data sets (AUC range, 0.83-0.87). Conclusion A model that combined an index created from pretreatment MRI-based imaging features quantitating ITH, C-radiomics score, and clinicopathologic variables showed good performance for predicting pCR to NAC in patients with breast cancer. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rauch in this issue.

Automatic segmentation of rectal tumors from MRI using multiscale densely connected convolutional neural network based on attention mechanism.

Rectal cancer is one of the most common malignancies in the gastrointestinal tract. Currently, magnetic resonance imaging has become a vital tool in diagnosing and treating patients with rectal cancer. Notably, early diagnosis of rectal cancer can help improve patient survival rate; however, the clinical expertize of physicians is a limiting factor. Therefore, we propose an attention-based multiscale densely connected convolutional neural network based on an attention mechanism to improve the accuracy of diagnosis by automatically segmenting rectal tumors from two-dimensional (2D) magnetic resonance images (MRI) using computer-aided diagnostic techniques. First, to address the inability of U-Net (a classical segmentation network for medical images) and extract rich semantic features and the inconsistent shape and size of tumors between different patients, we replace the conventional convolutional blocks in the U-Net network with multiscale densely connected convolutional blocks. Second, to make the network focus better on global contextual information, we add central blocks with atrous convolution in the final coding layer or the last coding layer. Finally, we add a hybrid attention mechanism to each decoder module to help the model focus on the features of the rectal tumor region. We validated the effectiveness of the proposed method using 3773 2D MRI datasets from 572 patients. The sensitivity, specificity, Dice correlation coefficient, and Hausdorff distance of MRI rectal tumor segmentation were 85.47%, 86.35%, 94.71%, and 7.88 mm, respectively. The results showed that the proposed method outperforms conventional approaches. Moreover, the proposed method has better segmentation results in the rectal tumor segmentation task and can provide physicians with the second-most important clinical diagnostic opinion.