Multiparametric MRI-Based Deep Learning Radiomics Model for Assessing 5-Year Recurrence Risk in Non-Muscle Invasive Bladder Cancer.

BACKGROUND: Accurately assessing 5-year recurrence rates is crucial for managing non-muscle-invasive bladder carcinoma (NMIBC). However, the European Organization for Research and Treatment of Cancer (EORTC) model exhibits poor performance. PURPOSE: To investigate whether integrating multiparametric MRI (mp-MRI) with clinical factors improves NMIBC 5-year recurrence risk assessment. STUDY TYPE: Retrospective. POPULATION: One hundred ninety-one patients (median age, 65 years; age range, 54-73 years; 27 females) underwent mp-MRI between 2011 and 2017, and received ≥5-year follow-ups. They were divided into a training cohort (N = 115) and validation/testing cohorts (N = 38 in each). Recurrence rates were 23.5% (27/115) in the training cohort and 23.7% (9/38) in both validation and testing cohorts. FIELD STRENGTH/SEQUENCE: 3-T, fast spin echo T2-weighted imaging (T2WI), single-shot echo planar diffusion-weighted imaging (DWI), and volumetric spoiled gradient echo dynamic contrast-enhanced (DCE) sequences. ASSESSMENT: Radiomics and deep learning (DL) features were extracted from the combined region of interest (cROI) including intratumoral and peritumoral areas on mp-MRI. Four models were developed, including clinical, cROI-based radiomics, DL, and clinical-radiomics-DL (CRDL) models. STATISTICAL TESTS: Student's t-tests, DeLong's tests with Bonferroni correction, receiver operating characteristics with the area under the curves (AUCs), Cox proportional hazard analyses, Kaplan-Meier plots, SHapley Additive ExPlanations (SHAP) values, and Akaike information criterion for clinical usefulness. A P-value <0.05 was considered statistically significant. RESULTS: The cROI-based CRDL model showed superior performance (AUC 0.909; 95% CI: 0.792-0.985) compared to other models in the testing cohort for assessing 5-year recurrence in NMIBC. It achieved the highest Harrell's concordance index (0.804; 95% CI: 0.749-0.859) for estimating recurrence-free survival. SHAP analysis further highlighted the substantial role (22%) of the radiomics features in NMIBC recurrence assessment. DATA CONCLUSION: Integrating cROI-based radiomics and DL features from preoperative mp-MRI with clinical factors could improve 5-year recurrence risk assessment in NMIBC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Multiparametric MR characterization for human epithelial growth factor receptor 2 expression in bladder cancer: an exploratory study.

PURPOSE: To investigate the application value of multiparametric MRI in evaluating the expression status of human epithelial growth factor receptor 2 (HER2) in bladder cancer (BCa). METHODS: From April 2021 to July 2023, preoperative imaging manifestations of 90 patients with pathologically confirmed BCa were retrospectively collected and analyzed. All patients underwent multiparametric MRI including synthetic MRI, DWI, from which the T1, T2, proton density (PD) and apparent diffusion coefficient (ADC) values were obtained. The clinical and imaging characteristics as well as quantitative parameters (T1, T2, PD and ADC values) between HER2-positive and -negative BCa were compared using student t test and chi-square test. The diagnostic efficacy of parameters in predicting HER2 expression status was evaluated by calculating the area under ROC curve (AUC). RESULTS: In total, 76 patients (mean age, 63.59 years ± 12.84 [SD]; 55 men) were included: 51 with HER2-negative and 25 with HER2-positive BCa. HER2-positive group demonstrated significantly higher ADC, T1, and T2 values than HER2-negative group (all P < 0.05). The combination of ADC values and tumor grade yielded the best diagnostic performance in evaluating HER2 expression level with an AUC of 0.864. CONCLUSION: The multiparametric MR characterization can accurately evaluate the HER2 expression status in BCa, which may further guide the determination of individualized anti-HER2 targeted therapy strategies.

Amide Proton Transfer-Weighted Imaging in Assessing the Aggressive and Proliferative Potential of Bladder Cancer.

BACKGROUND: Ki-67 and human epidermal growth factor receptor 2 (HER2) are known oncogenes involved in bladder cancer (BCa) patient risk stratification. Preoperative assessment of their expression level can assist in clinical treatment decision-making. Recently, amide proton transfer-weighted (APTw) MRI has shown promising potential in the diagnosis of several malignancies. However, few studies reported the value of APTw imaging in evaluating Ki-67 and HER2 status of BCa. PURPOSE: To investigate the feasibility of APTw MRI in assessing the aggressive and proliferative potential regarding the expression levels of Ki-67 and HER2 in BCa. STUDY TYPE: Retrospective. SUBJECTS: 114 patients (mean age, 64.78 ± 11.93 [SD] years; 97 men) were studied. FIELD STRENGTH/SEQUENCE: APTw MRI acquired by a three-dimensional fast-spin-echo sequence at 3.0 T MRI system. ASSESSMENT: Patient pathologic findings, included histologic grade and the expression status of Ki-67 and HER2, were reviewed by one uropathologist. The APTw values of BCa were independently measured by two radiologists and were compared between high-/low-tumor grade group, high-/low-Ki-67 expression group, and high-/low-HER2 expression group. STATISTICAL TESTS: The interclass correlation coefficient, independent sample t-test, Mann-Whitney U test, Spearman's rank correlation, and receiver operating characteristic curve (ROC) analysis were used. P < 0.05 was considered statistically significant. RESULTS: Significantly higher APTw values were found in high-grade BCa patients (7.72% vs. 4.29%, P < 0.001), high-Ki-67 expression BCa patients (8.40% vs. 3.25%, P < 0.001) and HER2 positive BCa patients (8.24% vs. 5.40%, P = 0.001). APTw values were positively correlated with Ki-67 (r = 0.769) and HER2 (r = 0. 356) expression status. The area under the ROC curve of the APTw values for detecting Ki-67 and HER2 expression status were 0.883 (95% CI: 0.790-0.945) and 0.713 (95% CI: 0.592-0.816), respectively. DATA CONCLUSIONS: APTw MRI is a potential method to assess the biological and proliferation potential of BCa. TECHNICAL EFFICACY: Stage 2.

Histogram analysis of MR quantitative parameters: are they correlated with prognostic factors in prostate cancer?

PURPOSE: To investigate the correlation between quantitative MR parameters and prognostic factors in prostate cancer (PCa). METHOD: A total of 186 patients with pathologically confirmed PCa who underwent preoperative multiparametric MRI (mpMRI), including synthetic MRI (SyMRI), were enrolled from two medical centers. The histogram metrics of SyMRI [T1, T2, proton density (PD)] and apparent diffusion coefficient (ADC) values were extracted. The Mann‒Whitney U test or Student's t test was employed to determine the association between these histogram features and the prognostically relevant factors. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the differentiation performance. Spearman's rank correlation coefficients were calculated to determine the correlations between histogram parameters and the International Society of Urological Pathology (ISUP) grade group as well as pathological T stage. RESULTS: Significant correlations were found between the histogram parameters and the ISUP grade as well as pathological T stage of PCa. Among these histogram parameters, ADC_minimum had the strongest correlation with the ISUP grade (r = - 0.481, p < 0.001), and ADC_Median showed the strongest association with pathological T stage (r = - 0.285, p = 0.008). The ADC_10th percentile exhibited the highest performance in identifying clinically significant prostate cancer (csPCa) (AUC 0.833; 95% CI 0.771-0.883). When discriminating between the status of different prognostically relevant factors, a significant difference was observed between extraprostatic extension-positive and -negative cancers with regard to histogram parameters of the ADC map (10th percentile, 90th percentile, mean, median, minimum) and T1 map (minimum) (p = 0.002-0.032). Moreover, histogram parameters of the ADC map (90th percentile, maximum, mean, median), T2 map (10th percentile, median), and PD map (10th percentile, median) were significantly lower in PCa with perineural invasion (p = 0.009-0.049). The T2 values were significantly lower in patients with seminal vesicle invasion (minimum, p = 0.036) and positive surgical margin (10th percentile, 90th percentile, mean, median, and minimum, p = 0.015-0.025). CONCLUSION: Quantitative histogram parameters derived from synthetic MRI and ADC maps may have great potential for predicting the prognostic features of PCa.

Radiomics nomogram for predicting disease-free survival after partial resection or radical cystectomy in patients with bladder cancer.

OBJECTIVES: To create a MRI-derived radiomics nomogram that combined clinicopathological factors and radiomics signature (Rad-score) for predicting disease-free survival (DFS) in patients with bladder cancer (BCa) following partial resection (PR) or radical cystectomy (RC), including lymphadenectomy (LAE). METHODS: Finally, 80 patients with BCa after PR or RC with LAE were enrolled. Patients were randomly split into training (n = 56) and internal validation (n = 24) cohorts. Radiomic features were extracted from T2-weighted, dynamic contrast-enhanced, diffusion-weighted imaging, and apparent diffusion coefficient sequence. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was applied to choose the valuable features and construct the Rad-score. The DFS prediction model was built using the Cox proportional hazards model. The relationship between the Rad-score and DFS was assessed using Kaplan-Meier analysis. A radiomics nomogram that combined the Rad-score and clinicopathological factors was created for individualized DFS estimation. RESULTS: In both the training and validation cohorts, the Rad-score was positively correlated with DFS (P < .001). In the validation cohort, the radiomics nomogram combining the Rad-score, tumour pathologic stage (pT stage), and lymphovascular invasion (LVI) achieved better performance in DFS prediction (C-index, 0.807; 95% CI, 0.713-0.901) than either the clinicopathological (C-index, 0.654; 95% CI, 0.467-0.841) or Rad-score-only model (C-index, 0.770; 95% CI, 0.702-0.837). CONCLUSION: The Rad-score was an independent predictor of DFS for patients with BCa after PR or RC with LAE, and the radiomics nomogram that combined the Rad-score, pT stage, and LVI achieved better performance in individual DFS prediction. ADVANCES IN KNOWLEDGE: This study provided a non-invasive and simple method for personalized and accurate prediction of DFS in BCa patients after PR or RC.

Amide Proton Transfer-Weighted MRI and Diffusion-Weighted Imaging in Bladder Cancer: A Complementary Tool to the VI-RADS.

RATIONALE AND OBJECTIVES: To investigate the feasibility of amide proton transfer-weighted (APTw) and diffusion-weighted Magnetic Resonance Imaging (MRI) as a means by which to add value to the Vesical Imaging Reporting and Data System (VI-RADS) for discriminating muscle invasive bladder cancer (MIBC) from nonmuscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: This prospective study enrolled participants with pathologically confirmed bladder cancer (BCa) who underwent preoperative multiparametric MRI, including APTw and diffusion-weighted MRI, from July 2020 to January 2023. The exclusion criteria were lesions smaller than 10 mm, missing smooth muscle layer in the operation specimen, neoadjuvant therapy before MRI, inadequate image quality, and malignancy other than urothelial neoplasm. Two radiologists independently assigned the VI-RADS score for each participant. Quantitative parameters derived from APTw and diffusion-weighted MRI were obtained by another two radiologists. Receiver operating characteristic (ROC) curve analysis with the area under the ROC curve (AUC) was performed to evaluate the diagnostic performances of quantitative parameters for discriminating BCa detrusor muscle invasion status. RESULTS: A total of 106 participants were enrolled (mean age, 64 ± 12 years [SD]; 90 men): 32 with MIBC and 74 with NMIBC. Lower apparent diffusion coefficient (ADC) values (0.88 × 10-3 mm2/s ± 0.12 vs. 1.08 × 10-3 mm2/s ± 0.25; P < 0.001) and higher APTw values (6.89% [interquartile range {IQR}, 5.05%-12.17%] vs. 3.61% [IQR, 2.23%-6.83%]; P < 0.001) were observed in the MIBC group. Compared to VI-RADS alone, both APTw (P = 0.003) and ADC (P = 0.020) values could improve the diagnostic performance of VI-RADS in differentiating MIBC from NMIBC. The combination of the three yielded the highest diagnostic performance (AUC, 0.93; 95% CI:0.87,0.97) for evaluating muscle invasion status. The addition of the APTw values to the combination of VI-RADS and ADC values notably improved the diagnostic performance for differentiating NMIBC from MIBC (VI-RADS+ADC vs. VI-RADS+APTw+ADC, P = 0.046). CONCLUSION: MRI parameters derived from APTw and diffusion-weighted MRI can be used to accurately assess muscle invasion status in BCa and provide additional value to VI-RADS.

Multiparametric MRI-based VI-RADS: can it predict 1- to 5-year recurrence of bladder cancer?

OBJECTIVES: To evaluate whether Vesical Imaging-Reporting And Data System (VI-RADS) scores based on multiparametric MRI (mp-MRI) can predict bladder cancer (BCa) recurrence. METHODS: In this retrospective study, 284 patients with pathologically confirmed bladder neoplasms from November 2011 to October 2020 were included. Two radiologists blindly and independently scored mp-MRI scans according to VI-RADS. Scoring inconsistency was resolved in consensus. The latest follow-up was completed in December 2022. Pearson's correlation analyses, independent-sample t-tests, and receiver operating characteristic analyses were performed to assess the efficacy of VI-RADS score for the 1- to 5-year recurrence prognostication. RESULTS: Based on the latest follow-up, 37 (of 284, 13.0%), 69 (of 284, 24.3%), 70 (of 234, 29.9%), 72 (of 190, 37.9%), and 63 (of 135, 46.7%) patients had cancer recurrence at 1- to 5-year follow-up, respectively. VI-RADS scores showed significantly intergroup differences between recurrent and nonrecurrent cases during 1- to 4-year surveillance (p < 0.05). The recurrence-free survival was significantly higher in patients with VI-RADS scores of 1 or 2, compared to those with scores of 3, 4, or 5 (p < 0.05). Areas under the receiver operating characteristic curves for 1- to 5-year recurrence prediction were 0.744, 0.686, 0.656, 0.595, and 0.536, respectively. VI-RADS score of 3 or more was the threshold for 1-year recurrence assessment, and VI-RADS more than 3 was the cutoff for 2-year recurrence prediction. CONCLUSION: VI-RADS score has potential in preoperative prognostication of BCa recurrence, but its predictive power decreases over time. CLINICAL RELEVANCE STATEMENT: VI-RADS has potential in bladder cancer recurrence assessment, but its prognostic value decreases over time. Patients with VI-RADS ≥ 3 may be more likely to recur in 1 or 2 years postoperatively, thus should be performed with intensive surveillances. KEY POINTS: • VI-RADS scores had significant differences in 1- to 4-year recurrent and nonrecurrent patient groups. • Patients with VI-RADS scores of ≤ 2 showed more favorable recurrence-free survival outcomes. • The prognostic value of VI-RADS score decreased over time for bladder cancer recurrence prediction.

Development and external validation of the multichannel deep learning model based on unenhanced CT for differentiating fat-poor angiomyolipoma from renal cell carcinoma: a two-center retrospective study.

PURPOSE: There are undetectable levels of fat in fat-poor angiomyolipoma. Thus, it is often misdiagnosed as renal cell carcinoma. We aimed to develop and evaluate a multichannel deep learning model for differentiating fat-poor angiomyolipoma (fp-AML) from renal cell carcinoma (RCC). METHODS: This two-center retrospective study included 320 patients from the First Affiliated Hospital of Sun Yat-Sen University (FAHSYSU) and 132 patients from the Sun Yat-Sen University Cancer Center (SYSUCC). Data from patients at FAHSYSU were divided into a development dataset (n = 267) and a hold-out dataset (n = 53). The development dataset was used to obtain the optimal combination of CT modality and input channel. The hold-out dataset and SYSUCC dataset were used for independent internal and external validation, respectively. RESULTS: In the development phase, models trained on unenhanced CT images performed significantly better than those trained on enhanced CT images based on the fivefold cross-validation. The best patient-level performance, with an average area under the receiver operating characteristic curve (AUC) of 0.951 ± 0.026 (mean ± SD), was achieved using the "unenhanced CT and 7-channel" model, which was finally selected as the optimal model. In the independent internal and external validation, AUCs of 0.966 (95% CI 0.919-1.000) and 0.898 (95% CI 0.824-0.972), respectively, were obtained using the optimal model. In addition, the performance of this model was better on large tumors (≥ 40 mm) in both internal and external validation. CONCLUSION: The promising results suggest that our multichannel deep learning classifier based on unenhanced whole-tumor CT images is a highly useful tool for differentiating fp-AML from RCC.

Potential clinical feasibility of synthetic MRI in bladder tumors: a comparative study with conventional MRI.

Background: Synthetic magnetic resonance imaging (MRI) can provide quantitative information about inherent tissue properties and synthesize tailored contrast-weighted images simultaneously in a single scan. This study aimed to investigate the clinical feasibility of synthetic MRI in bladder tumors. Methods: A total of 47 patients (37 males; mean age: 66±10 years old) with postoperative pathology-confirmed papillary urothelial neoplasms of the bladder were enrolled in this retrospective study. A 2-dimensional (2D) multi-dynamic multi-echo pulse sequence was performed for synthetic MRI at 3T. The overall image quality, lesion conspicuity, contrast resolution, resolution of subtle anatomic structures, motion artifact, blurring, and graininess of images were subjectively evaluated by 2 radiologists independently using a 5-point Likert scale for qualitative analysis. The signal intensity ratio (SIR), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured for quantitative analysis. Linear weighted Kappa, Wilcoxon's signed-rank test, and the Mann-Whitney U-test were used for statistical analysis. Results: The interobserver consistency was excellent (κ values: 0.607-1). Synthetic T1-weighted (syn-T1w) and synthetic T2-weighted (syn-T2w) images obtained scores of 4 in most subjective terms, which were relatively smaller than those of conventional images. The SIR and SNR of syn-T1w were significantly higher than those of con-T1w images (SIR 2.37±0.86 vs. 1.47±0.20, P<0.001; SNR 21.83±9.43 vs. 14.81±3.30, P<0.001). No difference was found in SIR between syn-T2w and conventional T2-weighted (con-T2w) images, whereas the SNR of the syn-T2w was significantly lower (8.79±4.06 vs. 26.49±6.80, P<0.001). Additionally, the CNR of synthetic images was significantly lower than that of conventional images (T1w 1.41±0.72 vs. 2.68±1.04; T2w 1.40±0.87 vs. 4.03±1.55, all P<0.001). Conclusions: Synthetic MRI generates morphologic magnetic resonance (MR) images with diagnostically acceptable image quality in bladder tumors, especially T1-weighted images with high image contrast of tumors relative to urine. Further technological improvements are needed for synthetic MRI to reduce noise. Combined with T1, T2, and proton density (PD) quantitative data, synthetic MRI has potential for clinical application in bladder tumors.

Quantitative analysis and hepatoprotective mechanism of Cistanche deserticola Y. C. Ma against alcohol-induced liver injury in mice.

Cistanche deserticola Y. C. Ma (CD), known as "desert ginseng", has been found to have hepatoprotective effect. This research aimed to investigate the quality control and its alleviating effect on alcoholic liver injury in mice. In this study, for the first time, a sensitive and efficient ultra-high-performance liquid chromatography with quadrupole ion-trap mass spectrometry (UPLC-Q-TRAP/MS) method was developed to rapidly characterize nine representative phenylethanoid glycosides (PhGs) in the CD extract within 14 min, offering a reference for the quality control standard of this plant. In addition, we found that the CD extract significantly inhibited the weight loss, decreased the liver index, and attenuated excessive lipid deposition, inflammatory and oxidative stress in the mice liver. With the help of the high-throughput lipidomics technique, we discovered that CD markedly reversed 17 lipid metabolites and their involved linoleic acid, arachidonic acid and glycerophospholipid metabolic pathways. As these metabolites are mainly associated with lipid metabolism and liver damage, we further used molecular biological tests to found that CD could regulate the upstream genes and proteins of the lipid metabolism pathway, including adenosine 5'-monophosphate-activated protein kinase (AMPK), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and peroxidase proliferators activate receptors α (PPARα). In conclusion, this study elucidates the modulatory effects of CD on lipid metabolism disorders in alcoholic fatty liver from holistic system and provides a reference for further research and development of CD as a therapeutic agent.

Quantitative MRI in distinguishing bladder paraganglioma from bladder leiomyoma.

PURPOSE: To investigate the feasibility of quantitative MRI in the differentiation of bladder paraganglioma from bladder leiomyoma. METHODS: From 2014 to 2021, 11 patients with bladder paraganglioma and 14 patients with bladder leiomyoma confirmed by surgical pathology were retrospectively collected. All patients underwent multiparametric scanning with a 3.0 T MR system. Quantitative parameters including the SI-ratio on T1WI between the solid component of tumours and piriformis, ADC value and E-rate of the solid component of tumours were assessed. Independent sample t test or Mann-Whitney U test was used to compare these parameters between the two groups. The diagnostic efficiency of the parameters was examined using ROC curve analysis and the DeLong test. RESULTS: There were significant differences in SI-ratio on T1WI (P < 0.001), ADC value (P = 0.002) and the E-rate (P = 0.040) between the paraganglioma group and the leiomyoma group. The cutoff value of SI-ratio on 3 leiomyoma was 1.241, and the AUC was 1.000 (0.858-1.000). The cutoff value of the ADC value was 0.979 × 10-3mm2/s, and the AUC was 0.907 (0.717-0.987). The cutoff value of E-rate was 98.7%, and the AUC was 0.714 (0.495-0.878). The AUCs of the SI-ratio on T1WI and ADC value were significantly higher than the E-rate AUC (P = 0.015 and 0.034, respectively). CONCLUSION: Quantitative MRI can effectively distinguish bladder paraganglioma from bladder leiomyoma with the SI-ratio on T1WI or ADC value.

The Additional Value of Tri-parametric MRI in Identifying Muscle-invasive Status in Bladder Cancer.

RATIONALE AND OBJECTIVES: Identification of muscle-invasive status (MIS) of bladder cancer (BCa) is critical for treatment decisions. The Vesical Imaging-Reporting and Data System (VI-RADS) has been widely used in preoperatively predicting MIS using tri-parametric MR imaging including T2-weighted (T2W), diffusion-weighted (DW), and dynamic contrast-enhanced (DCE) sequences. While the diagnostic values of radiomics features from bi-parametric MRI such as T2W + DW to identification of MIS have been reported, whether the tri-parametric MRI could provide additional diagnostic value to the radiomics prediction task, and how to integrate DCE features into the radiomics model, which is the objectives of this study, remain unknown. MATERIALS AND METHODS: Patients with postoperatively confirmed BCa lesions (150 in non-muscle-invasive BCa and 56 in muscle-invasive BCa groups) were retrospectively included. Their T2W, DW with apparent diffusion coefficient (ADC) maps, and DCE sequences were acquired using a 3.0T MR system. Regions of interest were manually depicted and VI-RADS scores were assessed by three radiologists. Three predictive models were developed by the radiomics features extracted from sequence combinations of T2W + DW (Model one), T2W + DCE (Model two), and T2W + DW + DCE (Model three), respectively, using the least absolute shrinkage and selection operator. The performance of each model was quantitatively assessed on both the training (n = 165) and testing (n = 41) cohorts. Then a 10 times five-fold cross validation was conducted to assess the overall performance. RESULTS: Three models achieved area under the curve of 0.888, 0.869, and 0.901 in the cross validation, respectively. The tri-parametric model performed significantly superior than the two bi-parametric models and VI-RADS. The analysis of feature coefficients derived from least absolute shrinkage and selection operator algorithm showed features from the tri-parametric MRI are effective in MIS discrimination. CONCLUSION: The tri-parametric MRI provides additional value to the radiomics-based identification of MIS.

A Genome-Wide Analysis of StTGA Genes Reveals the Critical Role in Enhanced Bacterial Wilt Tolerance in Potato During Ralstonia solanacearum Infection.

TGA is one of the members of TGACG sequence-specific binding protein family, which plays a crucial role in the regulated course of hormone synthesis as a stress-responsive transcription factor (TF). Little is known, however, about its implication in response to bacterial wilt disease in potato (Solanum tuberosum) caused by Ralstonia solanacearum. Here, we performed an in silico identification and analysis of the members of the TGA family based on the whole genome data of potato. In total, 42 StTGAs were predicted to be distributed on four chromosomes in potato genome. Phylogenetic analysis showed that the proteins of StTGAs could be divided into six sub-families. We found that many of these genes have more than one exon according to the conserved motif and gene structure analysis. The heat map inferred that StTGAs are generally expressed in different tissues which are at different stages of development. Genomic collinear analysis showed that there are homologous relationships among potato, tomato, pepper, Arabidopsis, and tobacco TGA genes. Cis-element in silico analysis predicted that there may be many cis-acting elements related to abiotic and biotic stress upstream of StTGA promoter including plant hormone response elements. A representative member StTGA39 was selected to investigate the potential function of the StTGA genes for further analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) assays indicated that the expression of the StTGAs was significantly induced by R. solanacearum infection and upregulated by exogenous salicylic acid (SA), abscisic acid (ABA), gibberellin 3 (GA3), and methyl jasmonate (MeJA). The results of yeast one-hybrid (Y1H) assay showed that StTGA39 regulates S. tuberosum BRI1-associated receptor kinase 1 (StBAK1) expression. Thus, our study provides a theoretical basis for further research of the molecular mechanism of the StTGA gene of potato tolerance to bacterial wilt.

Amide Proton Transfer-weighted MRI in Predicting Histologic Grade of Bladder Cancer.

Background Bladder cancer is classified into high and low grades with different clinical treatments and prognoses. Thus, accurate preoperative evaluation of the histologic grade through imaging techniques is essential. Purpose To investigate the potential of amide proton transfer-weighted (APTw) MRI in evaluating the grade of bladder cancer and to evaluate whether APTw MRI can add value to diffusion-weighted imaging (DWI) at MRI. Materials and Methods In this single-center prospective study, participants with pathologic analysis-confirmed bladder cancer with no previous treatment, lesions larger than 10 mm, and adequate MRI quality were enrolled from July 2020 to September 2021 in a university teaching hospital. All participants underwent preoperative multiparametric MRI, including APTw MRI and DWI. The mean APTw and apparent diffusion coefficient (ADC) values of the primary tumor were measured independently by two radiologists. Receiver operating characteristic curves were generated to evaluate the diagnostic performance of these quantitative parameters. Results In total, 83 participants (mean age, 64 years ± 13 [SD]; 72 men) were evaluated: 51 with high-grade and 32 with low-grade bladder cancer. High-grade bladder cancer showed higher APTw values (6% [IQR, 4%-12%] vs 2% [IQR, 1%-3%]; P < .001) and lower ADC values (0.92 × 10-3 mm2/sec ± 0.17 vs 1.21 × 10-3 mm2/sec ± 0.25; P < .001) than low-grade bladder cancer. The area under the receiver operating characteristic curve (AUC) of APTw and ADC for differentiating low- and high-grade bladder cancer was similar (0.84 for both; P = .94). Moreover, the combination of the two techniques improved the diagnostic performance (AUC, 0.93; all P = .01). Conclusion The combination of amide proton transfer-weighted and diffusion-weighted MRI has the potential to improve the histologic characterization of bladder cancer by differentiating low- from high-grade cancers. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Milot in this issue. An earlier incorrect version appeared online. This article was corrected on July 7, 2022.

Multiparametric MRI Evaluation of VI-RADS for Bladder Tumors Located at the Ureteral Orifice.

Background The Vesical Imaging Reporting and Data System (VI-RADS) based on multiparametric MRI scans standardizes preoperative bladder cancer staging. However, limitations have been reported for VI-RADS, particularly for ureteral orifice tumors. Purpose To investigate the diagnostic performance and interobserver agreement of VI-RADS in evaluating muscle invasion for bladder tumors located at the ureteral orifice. Materials and Methods In this retrospective study, patients with histopathologically confirmed bladder cancer occurring at the ureteral orifice from January 2012 to November 2021 were analyzed. Two blinded radiologists independently scored multiparametric MRI scans according to VI-RADS. Interobserver agreement of the VI-RADS scores was evaluated with weighted κ analysis. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of the VI-RADS scores in the prediction of muscle invasion. Results A total of 78 patients (mean age, 67 years ± 7 [SD]; age range, 46-90 years; 67 men) were included in the final analysis: 25 with non-muscle-invasive bladder cancer and 53 with muscle-invasive bladder cancer (MIBCa). At consensus reading, one (1%) case was scored as VI-RADS 1, 27 cases (35%) were scored as VI-RADS 2, six (8%) were scored as VI-RADS 3, 10 (13%) were scored as VI-RADS 4, and 34 (44%) were scored as VI-RADS 5. On comparison of the VI-RADS score with histopathologic findings, it was confirmed that the presence of muscle invasion was 0% (zero of one) for VI-RADS 1, 15% (four of 27) for VI-RADS 2, 83% (five of six) for VI-RADS 3, 100% (10 of 10) for VI-RADS 4, and 100% (34 of 34) for VI-RADS 5. The area under the receiver operating characteristic curve of VI-RADS in the detection of MIBCa was 0.96 (95% CI: 0.92, 1.00). Conclusion The Vesical Imaging Reporting and Data System could be used to accurately predict muscle invasion for bladder tumors occurring at the ureteral orifice. © RSNA, 2022 Online supplemental material is available for this article.

A Potential Nine-lncRNAs Signature Identification and Nomogram Diagnostic Model Establishment for Papillary Thyroid Cancer.

The purpose of our current study was to establish a long non-coding RNA(lncRNA) signature and assess its prognostic and diagnostic power in papillary thyroid cancer (PTC). LncRNA expression profiles were obtained from the Cancer Genome Atlas (TCGA). The key module and hub lncRNAs related to PTC were determined by weighted gene co-expression network analysis (WGCNA) and LASSO Cox regression analyses, respectively. Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis were implemented to analyze the possible biological processes and signaling pathways of hub lncRNAs. Associations between key lncRNA expressions and tumor-infiltrating immune cells were identified using the TIMER website, and proportions of immune cells in high/low risk score groups were compared. Kaplan-Meier Plotter was used to evaluate the prognostic significance of hub genes in PTC. A diagnostic model was conducted with logistic regression analysis, and its diagnostic performance was assessed by calibration/receiver operating characteristic curves and principal component analysis. A nine-lncRNAs signature (SLC12A5-AS1, LINC02028, KIZ-AS1, LINC02019, LINC01877, LINC01444, LINC01176, LINC01290, and LINC00581) was established in PTC, which has significant diagnostic and prognostic power. Functional enrichment analyses elucidated the regulatory mechanism of the nine-lncRNAs signature in the development of PTC. This signature and expressions of nine hub lncRNAs were correlated with the distributions of tumor infiltrating immune cells. A diagnostic nomogram was also established for PTC. By comparing with the published models with less than or equal to nine lncRNAs, our signature showed a preferable performace for prognosis prediction. In conclusion, our present research established an innovative nine-lncRNAs signature and a six-lncRNAs nomogram that might act as a potential indicator for PTC prognosis and diagnosis, which could be conducive to the PTC treatment.

Single-Cell Analyses Reveal Mechanisms of Cancer Stem Cell Maintenance and Epithelial-Mesenchymal Transition in Recurrent Bladder Cancer.

PURPOSE: Bladder cancer treatment remains a major clinical challenge due to therapy resistance and a high recurrence rate. Profiling intratumor heterogeneity can reveal the molecular mechanism of bladder cancer recurrence. EXPERIMENTAL DESIGN: Here, we performed single-cell RNA sequencing and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) on tumors from 13 patients with low recurrence risk, high recurrence risk, and recurrent bladder cancer. RESULTS: Our study generated a comprehensive cancer-cell atlas consisting of 54,971 single cells and identified distinct cell subpopulations. We found that the cancer stem-cell subpopulation is enriched during bladder cancer recurrence with elevated expression of EZH2. We further defined a subpopulation-specific molecular mechanism whereby EZH2 maintains H3K27me3-mediated repression of the NCAM1 gene, thereby inactivating the cell invasive and stemness transcriptional program. Furthermore, taking advantage of this large single-cell dataset, we elucidated the spectrum of epithelial-mesenchymal transition (EMT) in clinical samples and revealed distinct EMT features associated with bladder cancer subtypes. We identified that TCF7 promotes EMT in corroboration with single-cell ATAC with high-throughput sequencing (scATAC-seq) analysis. Additionally, we constructed regulatory networks specific to recurrent bladder cancer. CONCLUSIONS: Our study and analytic approaches herein provide a rich resource for the further study of cancer stem cells and EMT in the bladder cancer research field.