Multi-task deep learning based on T2-Weighted Images for predicting Muscular-Invasive Bladder Cancer.

BACKGROUND: An accurate preoperative assessment of Non-Muscle-Invasive Bladder Cancer (NMIBC) and Muscle-Invasive Bladder Cancer (MIBC) in Bladder Cancer (BCa) can help the urologist make diagnostic decisions. Considering the absence of multiparametric MRI for contrast medium allergy and economic reasons, this study aims to develop a deep learning method based on T2-Weighted (T2WI) images alone for predicting NMIBC and MIBC. METHOD: We propose a Multi-task BCa Muscular Invasion Prediction (MBMIP) model to discriminate MIBC from NMIBC. The three-channel-input including the original T2WI image, segmented bladder, and the region of interest can help the MBMIP model locate the bladder and pay more attention to the surrounding information of the tumor. Inception V3 is used as the feature extraction module, which uses multiple branches to extract high-level features with different degrees of abstraction. In addition, based on the idea of multi-task learning, a reconstruction block for T2WI images is also introduced to assist the backbone classification network to improve the classification performance. RESULTS: The entire data consist of retrospective data (390 cases), prospective data (39 cases), and multi-center data (39 cases). In the retrospective test, the accuracy, sensitivity, and specificity of the MBMIP model are 0.911, 0.889, and 0.920 respectively, while those of the prospective test are 0.923, 1.000, and 0.885. And in the muti-center test, the MBMIP model yields accuracy, sensitivity, and specificity of 0.846, 0.667, and 0.879. CONCLUSION: The MBMIP model could achieve a satisfactory prediction result in discriminating between NMIBC and MIBC, which may aid urologists in preoperative decision-making for BCa patients.

Quantitative multiparametric MRI as a promising tool for the assessment of early response to neoadjuvant chemotherapy in bladder cancer.

PURPOSE: Magnetic resonance imaging (MRI) has been applied to predict the neoadjuvant chemotherapy (NAC) response of bladder cancer at an early stage, but the performance remains poor. A tool for the selection of patients with muscle-invasive bladder cancer (MIBC) with high probability of benefitting from NAC is not yet available. We designed a prospective study to assess a quantitative MRI for predicting the early response of MIBC to NAC. METHODS: All individuals underwent a time-course MRI at pre-NAC, 24 h after initial cisplatin medication (24 h-NAC) and post-NAC.Chemosensitivity was evaluated according to pathological response.The transfer constant (Ktrans), plasma volume (Vp), extravascular extracellular space (Ve), and apparent diffusion coefficient (ADC) were quantitated based on dynamic contrast-enhanced and diffusion-weighted imaging.Quantitative RECIST criteria were constructed by modelling pre-NAC and 24 h-NAC MRI measures, and then compared with conventional RECIST by using pre- and post-NAC MRI measures. RESULTS: In this pilot study, a total of 24 patients were enrolled into the study. Eight patients were pathologically confirmed to be NAC-responders. After a thorough evaluation of these parameters, different parameters showed good discrimination at different point in time. ROC curves showed quantitative MRI can predict the response to NAC, especially ADC_M (AUC = 0.859, P = 0.005) and ADC index (AUC = 0.844, P = 0.007) at pre-NAC timing and ADC_M (AUC = 0.816, P = 0.013) at 24 h-NAC timing. Then, a qRECIST model was established for predicting NAC sensitivity, with AUC of 0.91, TP rate of 0.8, and accuracy of 0.75. CONCLUSION: The diagnostic performance of mpMRI parameters for NAC response is excellent. The qRECIST derived between pre- and 24 h NAC MRI could predict the early response of MIBC to NAC and help for candidate selection.

The application value of multi-parameter cystoscope in improving the accuracy of preoperative bladder cancer grading.

PURPOSE: To develop and validate a preoperative cystoscopic-based predictive model for predicting postoperative high-grade bladder cancer (BCa), which could be used to guide the surgical selection and postoperative treatment strategies. MATERIALS AND METHODS: We retrospectively recruited 366 patients with cystoscopy biopsy for pathology and morphology evaluation between October 2010 and January 2021. A binary logistic regression model was used to assess the risk factors for postoperative high-grade BCa. Diagnostic performance was analyzed by plotting receiver operating characteristic curve and calculating area under the curve (AUC), sensitivity, specificity. From January 2021 to July 2021, we collected 105 BCa prospectively to validate the model's accuracy. RESULTS: A total of 366 individuals who underwent transurethral resection of bladder tumor (TURBT) or radical cystectomy following cystoscopy biopsy were included for analysis. 261 (71.3%) had a biopsy pathology grade that was consistent with postoperative pathology grade. We discovered five cystoscopic parameters, including tumor diameter, site, non-pedicled, high-grade biopsy pathology, morphology, were associated with high-grade BCa. The established multi-parameter logistic regression model ("JSPH" model) revealed AUC was 0.917 (P < 0.001). Sensitivity and specificity were 86.2% and 84.0%, respectively. And the consistency of pre- and post-operative high-grade pathology was improved from biopsy-based 70.5% to JSPH model-based 85.2%. In a 105-patients prospective validation cohort, the consistency of pre- and post-operative high-grade pathology was increased from 63.1 to 84.2% after incorporation into JSPH model for prediction. CONCLUSION: The cystoscopic parameters based "JSPH model" is accurate at predicting postoperative pathological high-grade tumors prior to operations.

Cascade Path Augmentation Unet for bladder cancer segmentation in MRI.

BACKGROUND: Treatment choices for patients with bladder cancer (BCa) are determined by the presence of muscular invasion. The precise segmentation of the inner and outer walls (IW and OW), as well as the bladder tumor (BT), is crucial for improving computer-aided diagnosis of muscle-invasive bladder cancer (MIBC). PURPOSE: To propose a novel deep learning-based model to improve the segmentation accuracy of the IW, OW, and BT, which can be useful in clinical practice. METHODS: We proposed a Cascade Path Augmentation Unet (CPA-Unet) network to conduct multi-regional segmentation of the bladder using 1545 T2-weighted MRI scans. The model employs a cascade strategy to eliminate the redundant information in the background. Unet is used to segment the bladder from the background in the rough segmentation. The path augmentation structure is used in the fine segmentation to mine multi-scale features. Additionally, the partial dense connection is adopted as the skip connection module to concatenate the low- and high-level sematic features. RESULTS: The CPA-Unet is trained using 1391 T2WI slices and tested using 154 T2WI slices. In comparison to previous deep learning-based methods, the CPA-Unet achieves superior segmentation results in terms of Dice similarity coefficient (DSC) and Hausdorff distance (HD) (IW: DSC = 98.19%, HD = 2.07 mm; OW: DSC = 82.24%, HD = 2.62 mm; BT: DSC = 87.40%, HD = 0.76 mm). CONCLUSIONS: Our proposed CPA-Unet network is capable of segmenting the bladder into its IW and OW, as well as tumors. The segmentation results provide a reliable and effective foundation for computer-assisted clinical diagnosis of MIBC.

External validation of Pentafecta in patients undergoing laparoscopic radical cystectomy: results from a high-volume center.

BACKGROUND: To investigate whether Pentafecta is suitable for bladder cancer patients receiving laparoscopic radical cystectomy (LRC). METHODS: From November 2013 to December 2020, muscle invasive Bladder Cancer (MIBC) and non-muscle invasive Bladder Cancer (NMIBC) patients who received LRC and urinary diversion were retrospectively analyzed. Pentafecta was defined as meeting five criteria: negative soft margin, ≥ 16 lymph nodes (LNs) removed, major complications free, urinary diversion related sequelae free and clinical recurrence free within 1 year. Analyze the achievement of five criteria and compare the overall survival (OS) of Pentafecta group with non-attainment group. Multivariable Cox's regression was performed to evaluate the impact of Pentafecta on OS. Multivariable logistic regression was performed to explore the effect of surgical experience on Pentafecta attainment. RESULTS: A total of 340 patients were included, negative soft margin, ≥ 16 lymph nodes (LNs) removed, major complications free, urinary diversion related sequelae free and clinical recurrence free within 1 year were observed in 95.3%, 30.3%, 83.8%, 75.0% and 85.6% of patients, respectively. Pentafecta group had a significantly longer OS than the non-attainment group (P = 0.027). The group with 10-15 LNs removed and meeting the other four criteria had a similar OS to group with ≥ 16 LNs removed (Pentafecta group) (5-year OS: 67.3% vs 72.7%, P = 0.861). Pentafecta (HR = 0.33, P = 0.011), positive lymph nodes (HR = 2.08, P = 0.028) and MIBC (HR = 3.70, P < 0.001) were all significant predictors of OS in multivariable Cox's regression. Surgical experience (OR = 1.05, P < 0.001), conduit (OR = 2.09, P = 0.047) and neobladder (OR = 2.47, P = 0.048) were all independent predictors of Pentafecta attainment in multivariable logistic regression. CONCLUSIONS: Pentafecta is suitable for bladder cancer patients receiving LRC and has the potential to be a valuable tool for evaluating the quality of LRC. Based on Pentafecta analysis, removing 10 LNs instead of 16 LNs as the one of the five criteria may be more appropriate for bladder cancer patients.

Robot-Assisted Totally Intracorporeal Resection of Cutaneous Ureterostomy Tumor and Ileal Conduit Surgery: A Rare Case Report.

BACKGROUND: Radical cystectomy (RC) is the standard treatment for muscular invasive bladder cancer (MIBC) and some high-risk non-muscular invasive bladder cancer (NMIBC). Cutaneous ureterostomy is a common form of urinary diversion. However, after radical cystectomy, recurrence of upper urinary tract malignancies is possible. There is no relevant report on how to improve this situation's management. CASE PRESENTATION: This case is a 56-year-old male patient hospitalized due to the development of a new tumor in the ureteral cutaneous stoma following radical cystectomy for more than five years. A biopsy of the tumor revealed high-grade urothelial carcinoma. Computed tomography (CT) revealed that the local soft tissue around the cutaneous stoma was thickened, but no other lesions were visible. After evaluating the case, we chose robot-assisted completely intracorporeal resection of cutaneous ureterostomy tumor and ileal conduit surgery. The total time for the operation and the blood loss were 400 minutes and 150 ml, respectively. Following surgery, the patient got standard chemotherapy in combination with immunotherapy. Additionally, ten months following the surgery, the patient did not experience disease progression or complications. CONCLUSION: The robot-assisted operation is safe and feasible for upper urinary tract tumor recurrence following radical cystectomy with cutaneous ureterostomy.

Renal Functional and Perioperative Outcomes of Retroperitoneal Robot-Assisted Versus Laparoscopic Partial Nephrectomy with Segmental Renal Artery Clamping.

Background: Retroperitoneal approach and segmental renal artery clamping in partial nephrectomy are techniques that facilitate postoperative recovery and renal function preservation. This study aimed to compare the renal function preservation and perioperative outcomes of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) with these techniques. Materials and Methods: Clinical parameters of 43 patients who had undergone retroperitoneal RAPN from March 2017 to December 2019 were retrospectively collected and compared with those of 52 patients who had undergone retroperitoneal LPN at the same period in our institution. Differences in operating time, warm ischemia time, estimated blood loss, complications, postoperative hospital stay, as well as renal function loss were compared between the two groups. Results: Background characteristics between RAPN and LPN groups such as age, gender, BMI, and tumor characteristics were comparable. All RAPNs and LPNs were successfully completed without conversion to open surgery or nephrectomy. No significant difference in operating time, estimated blood loss, complications, and postoperative hospital stay was observed between RAPN and LPN groups. The warm ischemia time in RAPN group was slightly shorter than that of LPN groups (P = .054). Compared with the LPN group, the RAPN group was significantly associated with less glomerular filtration rate reduction and renal volume loss rate (P = .042 and P = .013, respectively). Conclusions: The perioperative outcomes were comparable between the two groups. However, compared with LPN, RAPN had superiority in preserving renal function in our series.

Robot-Assisted Laparoscopic Retroperitoneal Renal Artery Aneurysm Repair: A Rare Case Report and Literature Review.

INTRODUCTION: The treatment of renal artery aneurysms (RAAs) includes surgical repair and endovascular techniques. Surgical repair is divided into open surgery repair and laparoscopic surgery repair. Laparoscopic RAA has fewer postoperative complications than open surgery. Some experiences with robotic RAA repair via transperitoneal access have been recently reported. However, no report could be found on the treatment of retroperitoneal RAA with the da Vinci robot-assisted surgery thus far. CASE PRESENTATION: Here, the surgical management of an 8.6-mm right-sided RAA via robot-assisted laparoscopic retroperitoneal approach in a 58-year-old man who presented with flank discomfort is reported. The aneurysm was resected, and the renal artery was reconstructed. The total operative time was 2 h with a warm ischemia time of 25 min, and the estimated surgical blood loss was 50 mL. The patient resumed a regular diet on postoperative day 2, and the hospital stay lasted 5 days. No intraoperative nor postoperative morbidity was reported. Follow-up imaging and functional analysis demonstrated resolution of the aneurysm and preservation of renal function after 2.5 months. CONCLUSIONS: Robot-assisted laparoscopic retroperitoneal RAA repair is flexible and safe. The greatest advantage of retroperitoneal surgery is direct access to the renal artery. Furthermore, it could reduce the injury in the abdominal organs and avoid abdominal adhesion. This approach may also allow for improved postoperative recovery, reduce the morbidity correlated with transperitoneal RAA, and thus may be considered as an alternative to transperitoneal surgery for RAAs in the future.

An Artificial Intelligence System for the Detection of Bladder Cancer via Cystoscopy: A Multicenter Diagnostic Study.

BACKGROUND: Cystoscopy plays an important role in bladder cancer (BCa) diagnosis and treatment, but its sensitivity needs improvement. Artificial intelligence has shown promise in endoscopy, but few cystoscopic applications have been reported. We report a Cystoscopy Artificial Intelligence Diagnostic System (CAIDS) for BCa diagnosis. METHODS: In total, 69 204 images from 10 729 consecutive patients from 6 hospitals were collected and divided into training, internal validation, and external validation sets. The CAIDS was built using a pyramid scene parsing network and transfer learning. A subset (n = 260) of the validation sets was used for a performance comparison between the CAIDS and urologists for complex lesion detection. The diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values and 95% confidence intervals (CIs) were calculated using the Clopper-Pearson method. RESULTS: The diagnostic accuracies of the CAIDS were 0.977 (95% CI = 0.974 to 0.979) in the internal validation set and 0.990 (95% CI = 0.979 to 0.996), 0.982 (95% CI = 0.974 to 0.988), 0.978 (95% CI = 0.959 to 0.989), and 0.991 (95% CI = 0.987 to 0.994) in different external validation sets. In the CAIDS vs urologists' comparisons, the CAIDS showed high accuracy and sensitivity (accuracy = 0.939, 95% CI = 0.902 to 0.964; sensitivity = 0.954, 95% CI = 0.902 to 0.983) with a short latency of 12 seconds, much more accurate and quicker than the expert urologists. CONCLUSIONS: The CAIDS achieved accurate BCa detection with a short latency. The CAIDS may provide many clinical benefits, from increasing the diagnostic accuracy for BCa, even for commonly misdiagnosed cases such as flat cancerous tissue (carcinoma in situ), to reducing the operation time for cystoscopy.

Role of Vesical Imaging-Reporting and Data System in predicting muscle-invasive bladder cancer: A diagnostic meta-analysis.

The objective of this study is to systematically evaluate the diagnostic performance of the Vesical Imaging-Reporting and Data System for predicting muscle-invasive bladder cancer. Embase, PubMed and Web of Science were systematically searched from 1 September 2018 to 30 July 2021 to include proper studies. We included studies that included data on Vesical Imaging-Reporting and Data System and their associated pathological findings, and we assessed their quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The pooled sensitivity and specificity were calculated and plotted using hierarchical summary receiver operating characterisijutic modeling. Meta-regression analysis was carried out to detect heterogeneity. A total of 20 studies with 2725 patients were included. When the cut-off point was 3, the pooled sensitivity and specificity were 0.92 (0.89-0.94) and 0.85 (0.78-0.90), respectively, and 0.82 (0.75-0.88) and 0.95 (0.91-0.97), respectively, when the cut-off point was 4. The area under the curve was 0.95 and 0.95, respectively. Heterogeneity was substantially considerable in sensitivity and specificity. All subgroup variables, including patient number, study design, magnetic resonance imaging field strength, number of radiologists, surgery pattern, diffusion-weighted imaging, and dynamic contrast-enhanced magnetic resonance imaging, contributed to sensitivity heterogeneity when the cut-off point was 3 and specificity heterogeneity when the cut-off point was 4. Multiple image acquisition plane of diffusion-weighted imaging achieved a higher sensitivity than single image acquisition plane of diffusion-weighted imaging in both the Vesical Imaging-Reporting and Data System 3 and 4 groups, and higher specificity in the Vesical Imaging-Reporting and Data System 4 group. Another significant source of heterogeneity was the cut-off point. The diagnostic performance of the Vesical Imaging-Reporting and Data System for predicting muscle-invasive bladder cancer was excellent in both cut-off points of the Vesical Imaging-Reporting and Data System 3 and 4. Multiple image acquisition planes of diffusion-weighted imaging should be given more attention in the Vesical Imaging-Reporting and Data System.

CircFAM114A2 Promotes Cisplatin Sensitivity via miR-222-3p/P27 and miR-146a-5p/P21 Cascades in Urothelial Carcinoma.

INTRODUCTION: Circular RNAs (circRNAs) are non-coding RNAs that have the structure of a covalently closed loop. Increasing data have proven that circRNAs can influence the progression and chemotherapy sensitivity of tumors. Therefore, the underlying function and mechanisms of more circRNAs in progression and chemotherapy resistance are important. METHODS: We conducted RNA sequencing on five pairs of urothelial carcinoma samples and screened for circRNAs. CircFAM114A2 was found to be low expressed in urothelial carcinoma. The functions of circFAM114A2 in urothelial carcinoma were explored by cell cycle assay, IC50 determination assay, cell proliferation assay, apoptosis assay, and tumorigenesis assay. RESULTS: We discovered that the levels of circFAM114A2 were decreased in urothelial carcinoma cell lines and tissues. According to follow-up data, urothelial carcinoma patients with higher circFAM114A2 expression had better survival. Importantly, the levels of circFAM114A2 were associated with the histological grade of urothelial carcinoma. CircFAM114A2 could inhibit cell proliferation and block more urothelial carcinoma cells in the G1 phase and then increase the sensitivity of urothelial carcinoma to cisplatin chemotherapy. Mechanistically, circFAM114A2 directly sponged miR-222-3p/miR-146a-5p and subsequently influenced the expressions of the downstream target genes P27/P21, which, in turn, inhibited the progression of urothelial carcinoma and increased the sensitivity of cancer cells to cisplatin chemotherapy. CONCLUSION: CircFAM114A2 could inhibit progression and promote cisplatin sensitivity in urothelial carcinoma through novel circFAM114A2/miR-222-3p/P27 and circFAM114A2/miR-146a-5p/P21 pathways. CircFAM1142 has therefore great potential as a prognostic biomarker and therapeutic target for urothelial carcinoma.

ALKBH5 Inhibited Cell Proliferation and Sensitized Bladder Cancer Cells to Cisplatin by m6A-CK2α-Mediated Glycolysis.

N6-methyladenosine (m6A) is the most commonly occurring internal RNA modification to be found in eukaryotic mRNA and serves an important role in various physiological events. AlkB homolog 5 RNA demethylase (ALKBH5), an m6A demethylase, belongs to the AlkB family of dioxygenases and has been shown to specifically demethylate m6A in RNA, which is associated with a variety of tumors. However, its function in bladder cancer remains largely unclear. In the present study, we found that the expression of ALKBH5 was downregulated in bladder cancer tissues and cell lines. Low expression of ALKBH5 was correlated with the worse prognosis of bladder cancer patients. Furthermore, functional assays revealed that knockdown of ALKBH5 promoted bladder cancer cell proliferation, migration, invasion, and decreased cisplatin chemosensitivity in the 5637 and T24 bladder cancer cell lines in vivo and in vitro, whereas ALKBH5 overexpression led to the opposite results. Finally, ALKBH5 inhibited the progression and sensitized bladder cancer cells to cisplatin through a casein kinase 2 (CK2)α-mediated glycolysis pathway in an m6A-dependent manner. Taken together, these findings might provide fresh insights into bladder cancer therapy.

Clinical Application of Circulating Tumor Cells and Circulating Endothelial Cells in Predicting Bladder Cancer Prognosis and Neoadjuvant Chemosensitivity.

PURPOSE: To investigate the role of circulating rare cells (CRCs), namely, circulating tumor cells (CTCs) and circulating endothelial cells (CECs), in aiding early intervention, treatment decision, and prognostication in bladder cancer. METHODS: A total of 196 patients with pathologically confirmed bladder cancer, namely, 141 non-muscle invasive bladder cancer (NMIBC) and 55 muscle invasive bladder cancer (MIBC) patients. There were 32 patients who received cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Subtraction enrichment combined with immunostaining-fluorescence in situ hybridization (SE-iFISH) strategy was used for CTC/CEC detection. Kaplan-Meier analysis and Cox regression were used to evaluate the overall survival (OS) and recurrence-free survival (RFS). Receiver operator characteristic analysis was used to discriminate NAC sensitivity. RESULTS: CTCs and CECs were related to clinicopathological characteristics. Triploid CTCs, tetraploid CTCs, and total CECs were found to be higher in incipient patients than in relapse patients (P = 0.036, P = 0.019, and P = 0.025, respectively). The number of total CECs and large cell CECs was also associated with advanced tumor stage (P = 0.028 and P = 0.033) and grade (P = 0.028 and P = 0.041). Remarkably, tumor-biomarker-positive CTCs were associated with worse OS and RFS (P = 0.026 and P = 0.038) in NMIBC patients underwent TURBT. CECs cluster was an independent predictor of recurrence in non-high-risk NMIBC patients underwent TURBT (HR = 9.21, P = 0.040). For NAC analysis, pre-NAC tetraploid CTCs and small cell CTCs demonstrated the capability in discriminating NAC-sensitive from insensitive patients. Additionally, tetraploid CTCs and single CTCs elevated post-NAC would indicate chemoresistance. CONCLUSION: CTCs and CECs may putatively guide in diagnosis, prognosis prediction, and therapeutic decision-making for bladder cancer.

An Adaptive Multi-Channel Cooperative Data Transmission Scheduling in VANETs.

The Internet of Vehicle (IoV) technology is one of the most important technologies of modern intelligent transportation. The data transmission scheduling method is a research hotspot in the technology of IoV. It is a challenge to ensure the stability of data transmission due to fast network topology changes, high data transmission delays, and some other reasons. Aiming at the above problems, a multi-channel data transmission cooperative scheduling algorithm is proposed. First, construct a feasible interference map based on the data items sent and received by vehicles in the road scene. Second, assign channels to the nodes in the interference map based on the Signal-to-Interference-Noise-Ratio (SINR). Finally, the optimal multi-channel data transmission cooperative scheduling scheme is achieved through the ISing model. Simulation results show that compared with the traditional algorithm, the network service capacity is increased by about 31% and the service delay is reduced by about 20%. It ensures that emergency data is preferentially transmitted to the target vehicle and the maximum weighted service capacity of the network.

Mechanism of RNA modification N6-methyladenosine in human cancer.

Since the breakthrough discoveries of DNA and histone modifications, the field of RNA modifications has gained increasing interest in the scientific community. The discovery of N6-methyladenosine (m6A), a predominantly internal epigenetic modification in eukaryotes mRNA, heralded the creation of the field of epi-transcriptomics. This post-transcriptional RNA modification is dynamic and reversible, and is regulated by methylases, demethylases and proteins that preferentially recognize m6A modifications. Altered m6A levels affect RNA processing, degradation and translation, thereby disrupting gene expression and key cellular processes, ultimately resulting in tumor initiation and progression. Furthermore, inhibitors and regulators of m6A-related factors have been explored as therapeutic approaches for treating cancer. In the present review, the mechanisms of m6A RNA modification, the clinicopathological relevance of m6A alterations, the type and frequency of alterations and the multiple functions it regulates in different types of cancer are discussed.

Role of MicroRNA-124 as a Prognostic Factor in Multiple Neoplasms: A Meta-Analysis.

OBJECTIVE: MicroRNA-124 (miR-124) was revealed to be an attractive prognostic tumour biomarker in recent studies. However, the results remain inconclusive. Hence, this meta-analysis was carried out to clarify the precise predictive value of miR-124. MATERIALS AND METHODS: Relevant studies were searched in PubMed, EMBASE, Web of Science, and the Cochrane Library up to October 2018. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were extracted from the selected studies. RESULTS: A total of 29 articles investigating the correlation between miR-124 expression and prognosis were initially identified. The pooled HR for overall survival (OS) of high miR-124 expression in multiple cancers was 0.55 (95%CI = 0.50-0.61). Disease-free survival (DFS)/progression-free survival (HR = 0.48, 95%CI = 0.38-0.61) revealed a protective role of increased miR-124 expression. Epigenetic hypermethylation of miR-124 mediated the silencing of its expression, which is correlated significantly with unfavourable survival (OS: HR = 2.06, 95%CI = 1.68-2.53; DFS/recurrence-free survival: HR = 2.77, 95%CI = 1.85-4.16). CONCLUSIONS: Taken together, our results suggest that miR-124 plays an antioncogenic role in various tumors, such as lung cancer and colorectal cancer. If methylation of miR-124 could be prevented, progression and metastasis would be improved; thus, miR-124 may be a promising biomarker and novel therapeutic target. Further large-scale studies are needed to confirm this possible effect.

Prognostic Value of Lactate Dehydrogenase Expression in Different Cancers: A Meta-Analysis.

BACKGROUND: This meta-analysis was performed to elucidate the association between the expression of lactate dehydrogenase (LDH) and the prognosis of various malignant neoplasms. MATERIALS AND METHODS: Qualified studies were systematically identified from relevant databases, including PubMed, Cochrane Library, Embase, WanFang, and HowNet. A total of 17 eligible studies with 4,176 patients that complied with the inclusion criteria were enrolled in this meta-analysis. The 17 articles were published from 2011 to 2018. The hazard ratio (HR) and 95% confidence interval (95%CI) were obtained from the selected studies. RESULTS: The analysis that included all LDH-related studies showed a significant association with the overall survival (OS) outcome (HR = 1.74, P = 0.001) but exhibited an insignificant association with the disease-free survival (DFS) or recurrence-free survival (RFS) outcome (HR = 1.40, P = 0.072). High lactate dehydrogenase A (LDHA) expression was significantly relevant to inferior OS (HR = 1.88, 95%CI: 1.37-2.59) and DFS or RFS (HR = 1.56, 95%CI: 1.29-1.89). CONCLUSIONS: High LDH expression and the prognostic outcome of various cancer patients are significantly correlated. High LDHA expression is a promising biomarker for forecasting the survival of patients and the recurrence of different cancers in these patients. Further associative studies are required due to the complex role of LDH genes.

Lung cancer cells release high mobility group box 1 and promote the formation of neutrophil extracellular traps.

Lung cancer is the leading cause of cancer-associated mortality. Tumor-associated neutrophils represent a large portion of inflammatory cells within the lung tumor microenvironment. However, the roles of neutrophil extracellular traps (NETs) in lung cancer remain unclear. In the present study, it was identified that Lewis lung carcinoma cells actively released the danger-associated molecular pattern protein high mobility group box 1 (HMGB1). Furthermore, HMGB1 in lung cancer cell supernatants promoted the formation of neutrophil extracellular traps (NETs), which was dependent on Toll-like receptor 4 (TLR4). The downstream molecules of TLR4, including myeloid differentiation factor 88, TIR-domain-containing adapter-inducing interferon-ß, p38 mitogen-activated protein kinases (p38 MAPKs) and extracellular signal-regulated kinases (ERKs), were activated during the formation of NETs. In addition, inhibition of p38 MAPKs or ERKs significantly decreased NETs. Morphine, an additional ligand for TLR4, aggravated the NETs induced by lung cancer cells. The present study revealed novel mechanisms in tumor-associated NET formation.

Extracellular RNAs from lung cancer cells activate epithelial cells and induce neutrophil extracellular traps.

Neutrophil infiltration is frequently observed in lung cancer tissues. Extracellular RNAs (exRNAs) may facilitate tumor progression. The present study investigated the cross­talk of tumor exRNAs and neutrophil extracellular traps (NETs) in lung cancer. Lewis lung carcinoma (LLC) cells were cultured with the deprived sera. And the cell culture supernatants (CCS) were analyzed in vitro and in vivo. The results revealed that exRNAs from lung cancer CCS promoted the inflammatory cytokine interleukin­1ß and reduced the vascular cell adhesion molecule­1 expression in lung epithelial cells. Lung cancer CCS­treated epithelial cells induced the production of NETs. By contrast, NETs reduced the tight junction protein claudin­5 in epithelial cells. Furthermore, NETs caused the necrosis of epithelial cells, which resulted in the release of exRNAs. In mice, lung cancer cells instilled in the lung recruited neutrophils and initiated NETs. In patients with lung cancer, NETs were also observed. These results suggested that exRNAs in the cell culture supernatant may indirectly induce NETs and contribute to lung cancer oncogenesis.