SCL/TAL1 Interrupting locus (STIL) is a ciliary-related gene involved in regulating the cell cycle and duplication of centrioles in dividing cells. STIL has been found disordered in multiple cancers and driven carcinogenesis. However, the molecular mechanisms and biological functions of STIL in cancers remain ambiguous. Here, we systematically analyzed the genetic alterations, molecular mechanisms, and clinical relevance of STIL across >10,000 samples representing 33 cancer types in The Cancer Genome Atlas (TCGA) dataset. We found that STIL expression is up-regulated in most cancer types compared with their adjacent normal tissues. The expression dysregulation of STIL was affected by copy number variation, mutation, and DNA methylation. High STIL expression was associated with worse outcomes and promoted the progression of cancers. Gene Ontology (GO) enrichment analysis and Gene Set Variation Analysis (GSVA) further revealed that STIL is involved in cell cycle progression, Mitotic spindle, G2M checkpoint, and E2F targets pathways across cancer types. STIL expression was negatively correlated with multiple genes taking part in ciliogenesis and was positively correlated with several genes which participated with centrosomal duplication or cilia degradation. Moreover, STIL silencing could promote primary cilia formation and inhibit cell cycle protein expression in prostate and kidney cancer cell lines. The phenotype and protein expression alteration due to STIL silencing could be reversed by IFT88 silencing in cancer cells. These results revealed that STIL could regulate the cell cycle through primary cilia in tumor cells. In summary, our results revealed the importance of STIL in cancers. Targeting STIL might be a novel therapeutic approach for cancers.
Necroptosis is a regulated form of cell necroptotic process, playing a pivotal role in tumors. In renal cell cancer (RCC), inhibiting necroptosis could promote the proliferation of tumor cells. However, the molecular mechanisms and prognosis prediction of necroptotic-process-related genes in RCC are still unclear. In this study, we first identified the necroptotic process prognosisrelated genes (NPRGss) by analyzing the kidney renal clear cell carcinoma (KIRC) data in The Cancer Genome Atlas (TCGA, n=607). We systematically analyzed the expression alteration, clinical relevance, and molecular mechanisms of NPRGss in renal clear cell carcinoma. We constructed an NPRGs risk signature utilizing the least absolute shrinkage and selection operator (LASSO) Cox regression analysis on the basis of the expression of seven NPRGss. We discovered that the overall survival (OS) of KIRC patients differed significantly in high-or low-NPRGs-risk groups. The univariate/ multivariate Cox regression revealed that the NPRGs risk signature was an independent prognosis factor in RCC. The gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to explore the molecular mechanisms of NPRGss. Immune-/metabolism-related pathways showed differential enrichment in high-/low-NPRGs-risk groups. The E-MTAB-1980, TCGA-KIRP, GSE78220, the cohort of Alexandra et al., and IMvigor210 cohort datasets were respectively used as independent validation cohorts of NPRGs risk signature. The patients in high-or low-NPRGs-risk groups showed different drug sensitivity, immune checkpoint expression, and immune therapy response. Finally, we established a nomogram based on the NPRGs risk signature, stage, grade, and age for eventual clinical translation; the nomogram possesses an accurate and stable prediction effect. The signature could predict patients' prognosis and therapy response, which provides the foundation for further clinical therapeutic strategies for RCC patients.
Background The primary cilia (PC) is a microtubule-based and nonmotile organelle which protrudes from the surface of almost all mammalian cells. At present, PC has been found to be a deficiency or loss in multiple cancers. Restoring PC could be a novel targeting therapy strategy. Our research showed that PC was reduced in human bladder cancer (BLCA) cells, and PC deficiency promotes cell proliferation. However, the concrete mechanisms remain unknown. SCL/TAL1 interrupting locus (STIL), a PC-related protein, was screened in our previous study and could influence the cell cycle by regulating PC in tumor cells. In this study, we aimed to elucidate the function of STIL for PC to explore the underlying mechanism of PC in BLCA. Methods Public database analysis, western blot, and enzyme-linked immunosorbent assay (ELISA) were used to screen genes and explore gene expression alteration. Immunofluorescence and western blot were utilized to investigate PC. Wound healing assay, clone formation assay, and CCK-8 assay were used to explore cell migration, growth, and proliferation. The co-immunoprecipitation and western blot were employed to reveal the interaction of STIL and AURKA. Results We found that high STIL expression is correlated with poor outcomes of BLCA patients. Further analysis revealed that STIL overexpression could inhibit PC formation, activate SHH signaling pathways, and promote cell proliferation. In contrast, STIL-knockdown could promote PC formation, inactivate SHH signaling, and inhibit cell proliferation. Furthermore, we found that the regulatory functions of STIL for PC depend on AURKA. STIL could influence proteasome activity and maintain AURKA stabilization. AURKA-knockdown could reverse PC deficiency caused by STIL overexpression for PC in BLCA cells. We observed that co-knockdown in STIL and AURKA significantly enhanced PC assembly. Conclusion In summary, our result provides a potential therapy target for BLCA based on the restoration of PC.
To demonstrate the Tianjin Institute of Urology (TJIU) technique to place and remove the ureteral stent with extraction string after percutaneous nephrolithotomy (PCNL). Additionally, we aim to compare the pain experienced during stent removal, quality of life during stent retention, and stent-related complications between patients with and without extraction string. 65 patients were included in the final analysis in the string group constructed by the TJIU technique and 66 patients in the conventional double-J ureteral stent (non-string) group. All patients underwent the surgery in a prone position under general anesthesia. They completed the Ureteral Stent Symptom Questionnaire (USSQ) on postoperative days (POD) 7, as well as before their ureteral stent was removed. The visual analogue scale (VAS) pain score (0–10) was completed immediately after the removal of the ureteral stent. Moreover, a specialized person was responsible for recording stent-related complications. All patients completed the USSQ on POD 7, and we did not find a difference in scores in each field. However, there was a significant difference in the “sex” domain before removing the ureteral stent (4.34 vs 3.23; p = 0.01). Notably, the use of extraction string after PCNL could decrease the pain associated with stent removal significantly (mean VAS scores 1.45 vs 2.76; p < 0.01). Extraction string did not increase the incidence of stent-related complications. We concluded that placing a ureteral stent with an extraction string after PCNL reduces the pain of ureteral stent removal without increasing complications such as accidental removal of the stent, febrile urinary tract infection (UTI).
Background: The occurrence of abdominal distention after radical cystectomy (RC) is common. We sought to determine risk factors of abdominal distention after RC, and to establish a simple and reliable nomogram for clinical risk assessment.Methods: Clinical information on 139 patients who underwent RC from January 2020 to August 2021 was collected. The chi-square test, hypergeometric test, and univariate/multivariate logistic regression were utilized to explore the relationship between variables and abdominal distention after RC. A nomogram was then used to predict the probability of abdominal distension for the patients who underwent RC. Calibration and receiver operating characteristic (ROC) curves were used to evaluate the accuracy of the model. Results:We found that 35 patients (25%) occurred in abdominal distention after RC. Among the patients, 7 of them developed intestinal obstruction. Postoperative water fasting time and abdominal surgery history were independent risk factors for abdominal distension after surgery. Finally, we constructed a risk model to predict the probability of abdominal distension after surgery. This model showed good fitting and calibration and excellent diagnostic performance with an area under the curve (AUC) of 0.804. Conclusions:Postoperative water fasting time and abdominal surgery history were independent risk factors for abdominal distension after surgery. There was no significant difference in the incidence of postoperative abdominal distention between robot-assisted cystectomy and laparoscopic cystectomy.
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