Selection of M7G-related lncRNAs in kidney renal clear cell carcinoma and their putative diagnostic and prognostic role.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a common malignant tumor of the urinary system. This study aims to develop new biomarkers for KIRC and explore the impact of biomarkers on the immunotherapeutic efficacy for KIRC, providing a theoretical basis for the treatment of KIRC patients. METHODS: Transcriptome data for KIRC was obtained from the The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Weighted gene co-expression network analysis identified KIRC-related modules of long noncoding RNAs (lncRNAs). Intersection analysis was performed differentially expressed lncRNAs between KIRC and normal control samples, and lncRNAs associated with N(7)-methylguanosine (m7G), resulting in differentially expressed m7G-associated lncRNAs in KIRC patients (DE-m7G-lncRNAs). Machine Learning was employed to select biomarkers for KIRC. The prognostic value of biomarkers and clinical features was evaluated using Kaplan-Meier (K-M) survival analysis, univariate and multivariate Cox regression analysis. A nomogram was constructed based on biomarkers and clinical features, and its efficacy was evaluated using calibration curves and decision curves. Functional enrichment analysis was performed to investigate the functional enrichment of biomarkers. Correlation analysis was conducted to explore the relationship between biomarkers and immune cell infiltration levels and common immune checkpoint in KIRC samples. RESULTS: By intersecting 575 KIRC-related module lncRNAs, 1773 differentially expressed lncRNAs, and 62 m7G-related lncRNAs, we identified 42 DE-m7G-lncRNAs. Using XGBoost and Boruta algorithms, 8 biomarkers for KIRC were selected. Kaplan-Meier survival analysis showed significant survival differences in KIRC patients with high and low expression of the PTCSC3 and RP11-321G12.1. Univariate and multivariate Cox regression analyses showed that AP000696.2, PTCSC3 and clinical characteristics were independent prognostic factors for patients with KIRC. A nomogram based on these prognostic factors accurately predicted the prognosis of KIRC patients. The biomarkers showed associations with clinical features of KIRC patients, mainly localized in the cytoplasm and related to cytokine-mediated immune response. Furthermore, immune feature analysis demonstrated a significant decrease in immune cell infiltration levels in KIRC samples compared to normal samples, with a negative correlation observed between the biomarkers and most differentially infiltrating immune cells and common immune checkpoints. CONCLUSION: In summary, this study discovered eight prognostic biomarkers associated with KIRC patients. These biomarkers showed significant correlations with clinical features, immune cell infiltration, and immune checkpoint expression in KIRC patients, laying a theoretical foundation for the diagnosis and treatment of KIRC.

The effect of irrigation rate on intrarenal pressure in an ex vivo porcine kidney model-preliminary study with different flexible ureteroscopes and ureteral access sheaths.

INTRODUCTION: Ureteral access sheath (UAS) and irrigation are used in flexible ureteroscopy (fURS). Both conventional UAS (cUAS) and vacuum-assisted UAS (vaUAS) are currently available. Irrigation increases the intrarenal pressure (IRP). Our objectives were to study the effects of various irrigation rates on IRP using different sizes of fURS in different sizes and functions of UAS. MATERIALS AND METHODS: Ten freshly harvested porcine kidneys served as the study subjects. 11/13F and 12/14F cUAS and vaUAS with 2.8 mm and 3.2 mm fURS were experimented on in various scope/sheath combinations. 6F pressure monitor catheters were placed into upper, middle, and lower calyces. IRPs were recorded under different irrigation rates in cUAS and vaUAS, with either 150 or 300 mmHg aspiration pressures, and with air vent either open or closed. RESULTS: 12/14F cUAS with 2.8 mm fURS could maintain IRPs below 35 mmHg with irrigation rates up to 200 cc/min. With 3.2 mm fURS, the rate dropped to 110-120 cc/min. With 12/14F vaUAS and vent closed, the IRP remained less than 5 mmHg at 200 cc/min irrigation for both fURS. For 11/13F cUAS, the < 35 mmHg threshold for 2.8 mm fURS was 80-90 cc/min; for 3.2 mm fURS, it was 30-40 cc/min. For 11/13F vaUAS with vent closed, IRPs remained < 5 mmHg at 200 cc/min irrigation for both scopes. CONCLUSION: Both 12F cUAS and vaUAS can be used safely with 2.8 mm fURS up to 200 cc/min irrigation. With either a smaller sheath or a larger scope, vaUAS with vent closed can maintain IRP in a safe range up 200 cc/min irrigation. vaUAS with vent open performed marginally better than cUAS.