Background Glutamine metabolism (GM) is known to play a critical role in cancer development, including in lung adenocarcinoma (LUAD), although the exact contribution of GM to LUAD remains incompletely understood. In this study, we aimed to discover new targets for the treatment of LUAD patients by using machine learning algorithms to establish prognostic models based on GM-related genes (GMRGs). Methods We used the AUCell and WGCNA algorithms, along with single-cell and bulk RNA-seq data, to identify the most prominent GMRGs associated with LUAD. Multiple machine learning algorithms were employed to develop risk models with optimal predictive performance. We validated our models using multiple external datasets and investigated disparities in the tumor microenvironment (TME), mutation landscape, enriched pathways, and response to immunotherapy across various risk groups. Additionally, we conducted in vitro and in vivo experiments to confirm the role of LGALS3 in LUAD. Results We identified 173 GMRGs strongly associated with GM activity and selected the Random Survival Forest (RSF) and Supervised Principal Components (SuperPC) methods to develop a prognostic model. Our model’s performance was validated using multiple external datasets. Our analysis revealed that the low-risk group had higher immune cell infiltration and increased expression of immune checkpoints, indicating that this group may be more receptive to immunotherapy. Moreover, our experimental results confirmed that LGALS3 promoted the proliferation, invasion, and migration of LUAD cells. Conclusion Our study established a prognostic model based on GMRGs that can predict the effectiveness of immunotherapy and provide novel approaches for the treatment of LUAD. Our findings also suggest that LGALS3 may be a potential therapeutic target for LUAD.

/pdf/integrating-multiple-machine-learning-methods-to-construct-2030fwo2.pdf

Integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma

Background: Endometrial cancer (UCEC) is a highly heterogeneous gynecologic malignancy that exhibits variable prognostic outcomes and responses to immunotherapy. The Familial sequence similarity (FAM) gene family is known to contribute to the pathogenesis of various malignancies, but the extent of their involvement in UCEC has not been systematically studied. This investigation aimed to develop a robust risk profile based on FAM family genes (FFGs) to predict the prognosis and suitability for immunotherapy in UCEC patients. Methods: Using the TCGA-UCEC cohort from The Cancer Genome Atlas (TCGA) database, we obtained expression profiles of FFGs from 552 UCEC and 35 normal samples, and analyzed the expression patterns and prognostic relevance of 363 FAM family genes. The UCEC samples were randomly divided into training and test sets (1:1), and univariate Cox regression analysis and Lasso Cox regression analysis were conducted to identify the differentially expressed genes (FAM13C, FAM110B, and FAM72A) that were significantly associated with prognosis. A prognostic risk scoring system was constructed based on these three gene characteristics using multivariate Cox proportional risk regression. The clinical potential and immune status of FFGs were analyzed using CiberSort, SSGSEA, and tumor immune dysfunction and rejection (TIDE) algorithms. qRT-PCR and IHC for detecting the expression levels of 3-FFGs. Results: Three FFGs, namely, FAM13C, FAM110B, and FAM72A, were identified as strongly associated with the prognosis of UCEC and effective predictors of UCEC prognosis. Multivariate analysis demonstrated that the developed model was an independent predictor of UCEC, and that patients in the low-risk group had better overall survival than those in the high-risk group. The nomogram constructed from clinical characteristics and risk scores exhibited good prognostic power. Patients in the low-risk group exhibited a higher tumor mutational load (TMB) and were more likely to benefit from immunotherapy. Conclusion: This study successfully developed and validated novel biomarkers based on FFGs for predicting the prognosis and immune status of UCEC patients. The identified FFGs can accurately assess the prognosis of UCEC patients and facilitate the identification of specific subgroups of patients who may benefit from personalized treatment with immunotherapy and chemotherapy.

/pdf/fam-family-gene-prediction-model-reveals-heterogeneity-3e7iraif.pdf

FAM family gene prediction model reveals heterogeneity, stemness and immune microenvironment of UCEC

Maintenance of flexible ureteroscopes can involve high costs and administrative burden. Instrument fragility necessitates eventual repair, rendering scopes inaccessible during refurbishment. We conducted a multi-institutional prospective cohort study to identify perioperative factors influencing flexible ureteroscope durability. Patients undergoing flexible ureteroscopy (URS) at six United States endourology centers were enrolled between August 2014 and June 2015. Surgeon self-reported concern and satisfaction with scope performance as well as upward and downward angles of deflection for each scope tip were measured before and after each procedure. The need for scope repair was determined by the operating surgeon at the time of the procedure and recorded. 424 URS cases using 74 flexible ureteroscopes were identified. Scope repair was required in 28 cases (6.6%) involving 26 scopes (35.1%). Upon univariate analysis, shorter patient height, absence of guidewire use, presence of a ureteral access sheath (UAS), longer procedure time, larger stone size, lithotrite type, surgeon training level, and self-reported concern were associated with scope repair. Upon multivariate analysis, UAS use (OR = 2.53, p = 0.005) and degree loss of scope upward flexion during a case (OR = 1.02, p = 0.03) increased the odds of a scope needing repair while the use of safety guidewire decreased the odds of a scope repair (OR = 0.50, p = 0.045). Lithotrite use and surgeon concern were associated with degree loss of scope upward flexion. The use of a UAS, absence of a safety guidewire, and the loss of upward ureteroscope flexion should be considered when evaluating means of optimizing reusable ureteroscope durability.

/pdf/identifying-factors-associated-with-need-for-flexible-3tf5zsnh4j.pdf

Identifying factors associated with need for flexible ureteroscope repair: a Western Endourology STone (WEST) research consortium prospective cohort study

Background Bladder cancer is ranked the second most frequent tumor among urological malignancies. The research strived to establish a prognostic model based on endoplasmic reticulum stress (ERS)-related long non-coding RNA (lncRNA) in bladder cancer. Methods We extracted the ERS-related genes from the published research and bladder cancer data from the Cancer Genome Atlas database. ERS-related lncRNAs with prognostic significance were screened by univariate Cox regression, least absolute shrinkage and selection operator regression analysis and Kaplan-Meier method. Multivariate Cox analysis was leveraged to establish the risk score model. Moreover, an independent dataset, GSE31684, was used to validate the model’s efficacy. The nomogram was constructed based on the risk score and clinical variables. Furthermore, the biological functions, gene mutations, and immune landscape were investigated to uncover the underlying mechanisms of the ERS-related signature. Finally, we employed external datasets (GSE55433 and GSE89006) and qRT-PCR to investigate the expression profile of these lncRNAs in bladder cancer tissues and cells. Results Six ERS-related lncRNAs were identified to be closely coupled with patients’ prognosis. On this foundation, a risk score model was created to generate the risk score for each patient. The ERS-related risk score was shown to be an independent prognostic factor. And the results of GSE31684 dataset also supported this conclusion. Then, a nomogram was constructed based on risk scores and clinical characteristics, and proven to have excellent predictive value. Moreover, the gene function analysis demonstrated that ERS-related lncRNAs were closely linked to fatty extracellular matrix, cytokines, cell adhesion, and tumor pathways. Further analysis revealed the association of the 6-lncRNAs signature with gene mutations and immunity in bladder cancer. Finally, the external datasets and qRT-PCR verified high expressions of the ERS-related lncRNAs in bladder cancer tissues and cells. Conclusions Overall, our findings indicated that ERS-related lncRNAs, which may affect tumor pathogenesis in a number of ways, might be exploited to assess the prognosis of bladder cancer patients.

/pdf/comprehensive-analysis-of-the-endoplasmic-reticulum-stress-198qopjl.pdf

Comprehensive analysis of the endoplasmic reticulum stress-related long non-coding RNA in bladder cancer

OBJECTIVE The T.O.HO. scoring system was developed to predict stone-free status after flexible ureterenoscopy (fURS) lithotripsy applied for ureter and renal stones. This study aimed to perform the external validation of the T.O.HO. score in the Turkish population and propose a modification for this system. MATERIAL METHODS Patients who underwent fURS for kidney and ureteral stones between January 2017 and January 2020 were retrospectively analysed. The patient and stone characteristics and perioperative findings were noted. The T.O.HO. score was externally validated and compared with the STONE score. Stone-free parameters were evaluated with the multivariate analysis. Based on the results of this analysis, the T.O.HO. score was modified and internally validated. RESULTS A total of 621 patients were included in the study. The stone-free rate was determined as 79.8% (496/621) after fURS. The regression analysis showed that stone area had better predictive power than stone diameter (P = .025). Lower pole (reference), middle pole [odds ratio (OR) = 0.492 P = .016] and middle ureteral (OR = 0.227, P = .024) localisations, stone density (OR = 1.001, P < .001), and stone volume (OR = 1.008, P < .001) were determined as independent predictive markers for stone-free status. Based on the effect size of the stone surface area in the nomogram, stone volume was divided into five categories, at 1-point intervals. The AUC values of the T.O.HO., STONE, and modified T.O.HO. score in predicting stone-free status were calculated as 0.758, 0.634, and 0.821, respectively. The modified T.O.HO. created by adding stone volume was statistically significantly superior to the original version (ROC curve comparison, P < .001). CONCLUSION The T.O.HO. score effectively predicted stone-free status after fURS. However, modified T.O.HO. SS showed the best predictive performance compared with original T.O.HO. SS.

External validation of the T.O.HO. score and derivation of the modified T.O.HO. score for predicting stone-free status after flexible ureteroscopy in ureteral and renal stones.

To compare the safety and efficacy of retrograde intrarenal surgery (RIRS) and modified Ultra-mini percutaneous nephrolithotomy (UMP) in semi-supine combined lithotomy position for the management of 1.5–3.5 cm lower pole renal stones (LPSs). A total of 63 patients with 1.5–3.5 cm LPSs who underwent RIRS (n = 33) or modified UMP (n = 30) in diameter between January 2017 and January 2019 were analyzed retrospectively. Modified UMP was performed in semi-supine combined lithotomy position and a 9.5/11.5 F ureteral access sheath (UAS) was inserted during the procedure in order to maintain low pelvic pressure and to facilitate the removal of stone fragments. Base-line parameters, stone characteristics, illness condition, operation time, postoperative hemoglobin (Hb) drop, postoperative creatinine (Cr) elevation, length of hospital stay, length of postoperative hospital stay, stone-free rate (SFR) and complications were compared between the two groups. There were no significant differences between the two groups in base-line parameters, stone characteristics and illness condition. The mean operating time of RIRS group was longer than UMP group (95.61 ± 21.9 vs. 55.0 ± 16.1 min, p < 0.001). The mean postoperative Hb drop was less in RIRS group (7.42 ± 4.7 vs. 15.70 ± 9.8 g/L, p < 0.001). The length of hospital stay and postoperative hospital stay for RIRS were shorter than UMP (4.76 ± 1.1 vs. 5.83 ± 0.8 d, p < 0.001, 2.97 ± 0.9 vs. 4.07 ± 0.9 d, p < 0.001). The Early SFR was higher in UMP group (54.5 vs. 80.0%, p < 0.050) while SFR at 1-month and 3-months postoperatively was similar in both groups (p = 0.504, p = 0.675). There were no significant differences between the two groups in complications (p = 0.228). For patients with 1.5–3.5 cm LPSs, both modified UMP and RIRS are safe and viable. The modified UMP technique was used in this study, application semi-supine combined lithotomy position and the retention of UAS can improve the surgical efficiency and maintain low pressure perfusion in the kidney, which resulted in superior treatment efficacy. Therefore, we highly recommend this technique for LPSs with heavy stone burdens.

/pdf/comparative-analysis-of-retrograde-intrarenal-surgery-and-2400cldlco.pdf

Comparative analysis of retrograde intrarenal surgery and modified ultra-mini percutaneous nephrolithotomy in management of lower pole renal stones (1.5-3.5 cm).

Background Bladder cancer is the second most common malignant tumor in the urogenital system. The research investigated the prognostic role of immune-related long non-coding RNA (lncRNA) in bladder cancer. Methods We extracted 411 bladder cancer samples from The Cancer Genome Atlas database. Single-sample gene set enrichment analysis was employed to assess the immune cell infiltration of these samples. We recognized differentially expressed lncRNAs between tumors and paracancerous tissues, and differentially expressed lncRNAs between the high and low immune cell infiltration groups. Venn diagram analysis detected differentially expressed lncRNAs that intersected the above groups. LncRNAs with prognostic significance were identified by regression analysis. Multivariate Cox analysis was used to establish the risk score model. Then we established and evaluated the nomogram. Additionally, we performed gene set enrichment analysis to explore the potential functions of the screened lncRNAs in tumor pathogenesis. Results Three hundred and twenty differentially expressed lncRNAs were recognized. We randomly divided patients into the training data set and the testing data set at a 2: 1 ratio. In the training data set, 9 immune-related lncRNAs with prognostic significance were identified. The risk score model was constructed to classify patients as high- and low-risk cohorts. Patients in the low-risk cohort had better survival outcomes than those in the high-risk cohort. The nomogram was established based on the indicators including age, gender, tumor-node-metastases stage, and risk score. The model's predictive performance was confirmed by the receiver operating characteristic curve analysis, concordance index method, calibration curve, and decision curve analysis. The testing data set also achieved similar results. Bioinformatics analysis suggested that the 9-lncRNA signature was involved in the modulation of various immune responses, antigen processing and presentation, and T cell receptor signaling pathway. Conclusions Our study uncovered the prognostic value of immune-related lncRNAs for bladder cancer and showed that they may regulate tumor pathogenesis in various ways.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.4167

A robust signature of immune-related long non-coding RNA to predict the prognosis of bladder cancer.

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Comparative analysis of retrograde intrarenal surgery and modified ultra-mini percutaneous nephrolithotomy in management of lower pole renal stones (1.5-3.5 cm).

A robust signature of immune-related long non-coding RNA to predict the prognosis of bladder cancer.