Background Runt-related transcription factor 1 (RUNX1) is a vital regulator of mammalian expression. Despite multiple pieces of evidence indicating that dysregulation of RUNX1 is a common phenomenon in human cancers, there is no evidence from pan-cancer analysis. Methods We comprehensively investigated the effect of RUNX1 expression on tumor prognosis across human malignancies by analyzing multiple cancer-related databases, including Gent2, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), the Human Protein Atlas (HPA), UALCAN, PrognoScan, cBioPortal, STRING, and Metascape. Results Bioinformatics data indicated that RUNX1 was overexpressed in most of these human malignancies and was significantly associated with the prognosis of patients with cancer. Immunohistochemical results showed that most cancer tissues were moderately positive for granular cytoplasm, and RUNX1 was expressed at a medium level in four types of tumors, including cervical cancer, colorectal cancer, glioma, and renal cancer. RUNX1 expression was positively correlated with infiltrating levels of cancer-associated fibroblasts (CAFs) in 33 different cancers. Moreover, RUNX1 expression may influence patient prognosis by activating oncogenic signaling pathways in human cancers. Conclusion Our findings suggest that RUNX1 expression correlates with patient outcomes and immune infiltrate levels of CAFs in multiple tumors. Additionally, the increased level of RUNX1 was linked to the activation of oncogenic signaling pathways in human cancers, suggesting a potential role of RUNX1 among cancer therapeutic targets. These findings suggest that RUNX1 can function as a potential prognostic biomarker and reflect the levels of immune infiltrates of CAFs in human cancers.
Background The origin recognition complex (ORC), a six-subunit DNA-binding complex, participates in DNA replication in cancer cells. Specifically in prostate cancers, ORC participates the androgen receptor (AR) regulated genomic amplification and tumor proliferation throughout the entire cell cycle. Of note, ORC6, the smallest subunit of ORC, has been reported to be dysregulated in some types of cancers (including prostate cancer), however, its prognostic and immunological significances remain yet to be elucidated. Methods In the current study, we comprehensively investigated the potential prognostic and immunological role of ORC6 in 33 human tumors using multiple databases, such as TCGA, Genotype-Tissue Expression, CCLE, UCSC Xena, cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2 databases. Results ORC6 expression was significantly upregulated in 29 types of cancers compared to the corresponding normal adjacent tissues. ORC6 overexpression correlated with higher stage and worse prognostic outcomes in most cancer types analyzed. Additionally, ORC6 was involved in the cell cycle pathway, DNA replication, and mismatch repair pathways in most tumor types. A negative correlation was observed between the tumor endothelial cell infiltration and ORC6 expression in almost all tumors, whereas the immune infiltration of T regulatory cell was noted to be statistically positively correlated with the expression of ORC6 in prostate cancer tissues. Furthermore, in most tumor types, immunosuppression-related genes, especially TGFBR1 and PD-L1 (CD274), exhibited a specific correlation with the expression of ORC6. Conclusions This comprehensive pan-cancer analysis revealed that ORC6 expression serves as a prognostic biomarker and that ORC6 is involved in the regulation of various biological pathways, the tumor microenvironment, and the immunosuppression status in several human cancers, suggesting its potential diagnostic, prognostic, and therapeutic value in pan-cancer, especially in prostate adenocarcinoma.
Renal cell carcinoma (RCC) is a lethal urologic tumor commonly seen in men that best responds to partial nephrectomy. An enhanced understanding of the molecular pathogenesis of RCC can broaden treatment options and tumor prevention strategies. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that regulates several bioactive substances, and the present study aimed to identify the role of SIRT1/AMP-activated protein kinase (AMPK) signaling in RCC progression. SIRT1 expression was detected in 100 patients with RCC using tissue microarray immunohistochemistry. SIRT1-knockdown and overexpression were performed via RNA interference and plasmid transfection. Inhibition of AMPK was used for the phenotypic rescue assays to verify whether AMPK was a downstream target of SIRT1. Reverse transcription-quantitative PCR was performed to verify transfection efficiency. Transwell, MTT and flow cytometry apoptosis assays were performed to evaluate the migration, invasion, proliferation and early apoptosis level of RCC cells. SIRT1 and AMPK protein expression in human RCC tissues and cell lines (786-O and ACHN) was detected using western blotting and immunofluorescence staining. The current results, combined with data from The Cancer Genome Atlas database, revealed that SIRT1 expression in RCC tissues was downregulated compared with in adjacent normal tissues. Additionally, high SIRT1 expression was associated with an improved prognosis in patients with RCC. Overexpression of SIRT1 inhibited the proliferation, migration and invasion of RCC cell lines and induced apoptosis, while inhibition of SIRT1 expression had the opposite effects. Further experiments indicated that SIRT1 may serve an anticancer role by upregulating the expression levels of downstream AMPK, thus revealing a potential therapeutic target for RCC.
Background This study aimed to compare the clinical outcomes of patients who underwent three-port laparoscopic radical cystectomy (LRC) with orthotopic neobladder (ONB) and traditional five-port method. Methods From January 2017 to November 2020, 100 patients underwent LRC + ONB at a third-level grade A hospital. Results Our study included 55 patients who underwent three-port LRC and 45 patients who underwent the five-port method. There were no significant differences in perioperative data such as operation time (253.00 ± 43.89 vs. 259.07 ± 52.31 min, P = 0.530), estimated blood loss (EBL)(97.64 ± 59.44 vs. 106.67 ± 55.35 min, P = 0.438), day to flatus (2.25 ± 1.49 vs. 2.76 ± 1.77 days, P = 0.128), day to regular diet (7.07 ± 2.99 vs. 7.96 ± 3.32 days, P = 0.165), day to pelvic drain removal (9.58 ± 3.25 vs. 10.53 ± 3.80 days, P = 0.180), and hospital stay after operation (11.62 ± 3.72 vs. 11.84 ± 4.37 days, P = 0.780) between the two groups. The only significant difference was in the treatment cost (P = 0.035). Similarly, postoperative complications, quality of life, and tumor outcomes were not significantly different between the two groups (P > 0.05). Conclusions The three-port method is safe and feasible for patients suitable for traditional five-port LRC with an orthotopic neobladder.
Background The need for the left ureter to pass through the subsigmoid during ileal conduit diversion surgery has not been investigated in any studies. A modified technique is simply used in the ileal conduit with the left ureter straight over the sigmoid colon due to the possible damage and lack of scientifically validated advantages of this procedure. Our study aimed to investigate the feasibility of the suggested surgical technique, as well as to evaluate perioperative outcomes and postoperative complications with a focus on the prevalence of small bowel obstruction (SBO) and ureteroileal anastomotic stricture (UAS). Methods A prospective single-center cohort of 84 consecutive patients undergoing laparoscopic radical cystectomy (LRC) and ileal conduit urinary diversion was conducted between January 2018 and April 2020. The incidence of SBO and UAS, perioperative outcomes, and postoperative complications were compared between a trial group of 30 patients receiving the modified procedure and a control group of 54 patients receiving the conventional Bricker ileal conduit. Results The two groups were comparable concerning patient characteristics and clinicopathologic features. No differences were observed in terms of the operation time, perioperative outcomes, and short-term (< 90 days) postoperative complications between the two groups. There were no occurrences of UAS in the modified group, while there were two cases (3.70%) in the patients who received Bricker's ureteroileal anastomosis (p = 0.535). Conclusion In the present study, a simple and feasible modified technique of ileal conduit is proposed. Compared with traditional techniques, our method has several advantages, including the ability to avoid compression of the left ureter from the mesentery without establishing a retrosigmoid tunnel, a low rate of UAS, and the ability to perform a secondary operation at long-term follow-up.
Background This study aimed to evaluate the effect of the three-port approach and conventional five-port laparoscopic radical cystectomy (LRC) with an ileal conduit. Methods Eighty-four patients, who were diagnosed with high-risk non-muscle-invasive and muscle-invasive bladder carcinoma and underwent LRC with an ileal conduit between January 2018 and April 2020, were retrospectively evaluated. Thirty and fifty-four patients respectively underwent the three-port approach and five-port LRC. Clinical characteristics, pathological data, perioperative outcomes, and follow-up data were analysed. Results There were no differences in perioperatively surgical outcome, including pathology type, prostate adenocarcinoma incidence, tumour staging, and postoperative creatinine levels between the two groups. The operative time (271.3 ± 24.03 vs. 279.57 ± 48.47 min, P = 0.299), estimated blood loss (65 vs. 90 mL, P = 0.352), time to passage of flatus (8 vs. 10 days, P = 0.084), and duration of hospitalisation post-surgery (11 vs. 12 days, P = 0.922) were no clear difference between both groups. Compared with the five-port group, the three-port LRC group was related to lower inpatient costs (12 453 vs. 14 134 $, P = 0.021). Our follow-up results indicated that the rate of postoperative complications, 90-day mortality, and the oncological outcome did not show meaningful differences between these two groups. Conclusions Three-port LRC with an ileal conduit is technically safe and feasible for the treatment of bladder cancer. On comparing the three-port LRC with the five-port LRC, our technique does not increase the rate of short-term and long-term complications and tumour recurrence, but the treatment costs of the former were reduced.
Background: No research has explored the need for the left ureter to be passed through the subsigmoid in ileal conduit diversion surgery. Due to the potential harm and lack of proven benefits of this practice, we used a simple modified technique in ileal conduit with the left ureter directly over the sigmoid colon. To investigate the feasibility of our surgical technique, as well as to evaluate perioperative outcomes and postoperative complications with a focus on the rate of small bowel obstruction (SBO) and ureteroileal anastomotic stricture (UAS).Methods: Between January 2018 and April 2020, a prospective single-center cohort of 84 consecutive patients undergoing laparoscopic radical cystectomy (LRC) and ileal conduit urinary diversion was analyzed. A study group of 30 patients receiving the modified technique was compared with a control group of 54 patients receiving the standard Bricker ileal conduit, and the differences in the incidence of SBO and UAS, perioperative results, and postoperative complications were analyzed.Results: The two groups were comparable concerning patient characteristics and clinicopathologic features. No differences were observed in terms of the operation time, perioperative outcomes, and short-term (<90 days) postoperative complications between the two groups. No case of UAS was observed in the modified group, whereas two (3.70%) cases of UAS (p = 0.535) occurred in the patients who underwent Bricker’s ureteroileal anastomosis.Conclusion: In our study, we describe a simple and feasible modified technique in ileal conduit. Compared with traditional techniques, our method has some advantages, including the ability to avoid compression of the left ureter from the mesentery without establishing a retrosigmoid tunnel, a low rate of UAS, and the ability to perform a secondary operation in the long-term follow-up.
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