Extrachromosomal circular DNAs in prostate adenocarcinoma: global characterizations and a novel prediction model.

Background: The role of focal amplifications and extrachromosomal circular DNA (eccDNA) is still uncertain in prostate adenocarcinoma (PRAD). Here, we first mapped the global characterizations of eccDNA and then investigate the characterization of eccDNA-amplified key differentially expressed encoded genes (eKDEGs) in the progression, immune response and immunotherapy of PRAD. Methods: Circular_seq was used in conjunction with the TCGA-PRAD transcriptome dataset to sequence, annotate, and filter for eccDNA-amplified differentially expressed coding genes (eDEGs) in PRAD and para-cancerous normal prostate tissues. Afterwards, risk models were created and eKDEGs linked to the PRAD prognosis were identified using Cox and Lasso regression analysis. The immune microenvironment of the risk model was quantified using a variety of immunological algorithms, which also identified its characteristics with regard to immunotherapy, immune response, and immune infiltration. Results: In this research, there was no significant difference in the size, type, and chromosomal distribution of eccDNA in PRAD and para-cancerous normal prostate tissues. However, 4,290 differentially expressed eccDNAs were identified and 1,981 coding genes were amplified. Following that, 499 eDEGs were tested in conjunction with the transcriptome dataset from TCGA-PRAD. By using Cox and Lasso regression techniques, ZNF330 and PITPNM3 were identified as eKDEGs of PRAD, and a new PRAD risk model was conducted based on this. Survival analysis showed that the high-risk group of this model was associated with poor prognosis and validated in external data. Immune infiltration analysis showed that the model risks affected immune cell infiltration in PRAD, not only mediating changes in immune cell function, but also correlating with immunophenotyping. Furthermore, the high-risk group was negatively associated with anti-CTLA-4/anti-PD-1 response and mutational burden. In addition, Tumor Immune Dysfunction and Exclusion analyses showed that high-risk group was more prone to immune escape. Drug sensitivity analyses identified 10 drugs, which were instructive for PRAD treatment. Conclusion: ZNF330 and PITPNM are the eKDEGs for PRAD, which can be used as potential new prognostic markers. The two-factor combined risk model can effectively assess the survival and prognosis of PRAD patients, but also can predict the different responses of immunotherapy to PRAD patients, which may provide new ideas for PRAD immunotherapy.

circTP63 promotes prostate cancer progression via miR-421/VAMP associated protein A axis.

Background: Circular RNAs (circRNA) have a vital role in the progression of cancers. For instance, circTP63 is upregulated in prostate cancer (PCa) tissues compared with adjacent normal tissues. However, the role of circTP63 in prostate cancer is still unclear. Methods: qRT-PCR assays were applied to detected the expression of circTP63 and miR-421 in PCa samples. Functionally, CCK-8, apoptosis assay, and transwell migration and invasion assays were used to explore the role of circTP63 in PCa progression. Mechanistically, the interaction between circTP63 and miR-421 were verified using qRT-PCR and dual-luciferase report assay. Western blot, qRT-PCR, and dual-luciferase report assay were applied to detect the interaction between miR-421 and VAMP associated protein A (VAPA). And xenograft animal model was used to detect the role of circTP63 in vivo. Results: circTP63 was upregulated and miR-421 was downregulated in PCa tissues. Functional assays revealed that circTP63 promoted the proliferation and metastasis of PCa cells in vitro. In addition, the inhibition effect of circTP63 knockdown could be rescued by miR-421 inhibition or VAPA overexpression. Mechanistically, circTP63-mediated PCa progression through directly binding to miR-421, and subsequently releasing the VAPA. In vivo, silencing of circTP63 significantly impaired PCa progression. Conclusion: In summary, our study identified circTP63 as an oncogenic circRNA, which could be a promising diagnostic and therapeutic target for PCa treatment.

Multiple omics integrative analysis identifies GARS1 as a novel prognostic and immunological biomarker: from pan-cancer to bladder cancer.

Glycyl-tRNA synthetase (GARS1) is differentially expressed across cancers. In this study, the value of GARS1 in the diagnosis and prognosis of various cancers was comprehensively evaluated by multiple omics integrative pan-cancer analysis and experimental verification. Through Kaplan-Meier, ROC and multiple databases, we explored GARS1 expression and prognostic and diagnostic patterns across cancers. The GARS1 relative reaction network was identified in PPI, GO, KEGG, methylation models and the genetic mutation atlas. Further research on the GARS1 value in bladder urothelial carcinoma (BLCA) was conducted by regression and nomogram models. We further analyzed the correlation between GARS1 and immune markers and cells in BLCA. Finally, in vitro experiments were used to validate GARS1 the oncogenic function of GARS1 in BLCA. We found that GARS1 was highly expressed across cancers, especially in BLCA. GARS1 expression was correlated with poor survival and had high diagnostic value in most tumor types. GARS1 is significantly associated with tRNA-related pathways whose mutation sites are mainly located on tRNA synthetase. In addition, Upregulation of GARS1 was connected with immune cell infiltration and five key MMR genes. M2 macrophages, TAMs, Th1 and T-cell exhaustion, and marker sets associated with GARS1 expression indicated specific immune infiltration in BLCA. Finally, in vitro experiments validated that GARS1 expression promotes BLCA cell proliferation and metastasis and inhibits apoptosis. Overall, GARS1 can be a novel prognostic and immunological biomarker through multiple omics integrative pan-cancer analysis. The expression of GARS1 in BLCA was positively correlated with specific immune infiltration, indicating that GARS1 might be related to the tumor immune microenvironment.

Establishment of a SUMO pathway related gene signature for predicting prognosis, chemotherapy response and investigating the role of EGR2 in bladder cancer.

Background: Bladder cancer is a prevalent malignancy with significant clinical implications. Small Ubiquitin-like Modifier (SUMO) pathway related genes (SPRG) have been implicated in the development and progression of cancer. Methods: In this study, we conducted a comprehensive analysis of SPRG in bladder cancer. We analyzed gene expression and prognostic value of SPRG and developed a SPRG signature (SPRGS) prognostic model based on four genes (HDAC4, TRIM27, EGR2, and UBE2I) in bladder cancer. Furthermore, we investigated the relationship between SPRGS and genomic alterations, tumor microenvironment, chemotherapy response, and immunotherapy. Additionally, we identified EGR2 as a key SPRG in bladder cancer. The expression of EGR2 in bladder cancer was detected by immunohistochemistry, and the cell function experiment clarified the effect of knocking down EGR2 on the proliferation, invasion, and migration of bladder cancer cells. Results: Our findings suggest that SPRGS hold promise as prognostic markers and predictive biomarkers for chemotherapy response and immunotherapy efficacy in bladder cancer. The SPRGS prognostic model exhibited high predictive accuracy for bladder cancer patient survival. We also observed correlations between SPRG and genomic alterations, tumor microenvironment, and response to chemotherapy. Immunohistochemical results showed that EGR2 was highly expressed in bladder cancer tissues, and its overexpression was associated with poor prognosis. Knockdown of EGR2 inhibited bladder cancer cell proliferation, invasion, and migration. Conclusion: This study provides valuable insights into the landscape of SPRGS in bladder cancer and their potential implications for personalized treatment strategies. The identification of EGR2 as a key SPRG and its functional impact on bladder cancer cells further highlights its significance in bladder cancer development and progression. Overall, SPRGS may serve as important prognostic markers and predictive biomarkers for bladder cancer patients, guiding treatment decisions and improving patient outcomes.

Revealing the potential of solute carrier family 31 (copper transporters), member 1: Insights into its role in bladder cancer progression and therapeutic implications.

Introduction: Bladder cancer represents a significant public health concern with diverse genetic alterations influencing disease onset, progression, and therapy response. In this study, we explore the multifaceted role of Solute Carrier Family 31 Member 1 (SLC31A1) in bladder cancer, a pivotal gene involved in copper homeostasis. Methods: Our research involved analyzing the SLC31A1 gene expression via RT-qPCR, promoter methylation via targeted bisulfite sequencing, and mutational status via Next Generation Sequencing (NGS) using the clinical samples sourced by the local bladder cancer patients. Later on, The Cancer Genome Atlas (TCGA) datasets were utilized for validation purposes. Moreover, prognostic significance, gene enrichment terms, and therapeutic drugs of SLC31A1 were also explored using KM Plotter, DAVID, and DrugBank databases. Results: We observed that SLC31A1 was significantly up-regulated at both the mRNA and protein levels in bladder cancer tissue samples, suggesting its potential involvement in bladder cancer development and progression. Furthermore, our investigation into the methylation status revealed that SLC31A1 was significantly hypomethylated in bladder cancer tissues, which may contribute to its overexpression. The ROC analysis of the SLC31A1 gene indicated promising diagnostic potential, emphasizing its relevance in distinguishing bladder cancer patients from normal individuals. However, it is crucial to consider other factors such as cancer stage, metastasis, and recurrence for a more accurate evaluation in the clinical context. Interestingly, mutational analysis of SLC31A1 demonstrated only benign mutations, indicating their unknown role in the SLC31A1 disruption. In addition to its diagnostic value, high SLC31A1 expression was associated with poorer overall survival (OS) in bladder cancer patients, shedding light on its prognostic relevance. Gene enrichment analysis indicated that SLC31A1 could influence metabolic and copper-related processes, further underscoring its role in bladder cancer. Lastly, we explored the DrugBank database to identify potential therapeutic agents capable of reducing SLC31A1 expression. Our findings unveiled six important drugs with the potential to target SLC31A1 as a treatment strategy. Conclusion: Our comprehensive investigation highlights SLC31A1 as a promising biomarker for bladder cancer development, progression, and therapy.

A novel entire traction method with clip-anchored nylon ring facilitating endoscopic submucosal dissection (ESD) of early gastric cancer.

A 48-year-old woman with a high-grade intraepithelial neoplasia of the gastric antrum was referred for ESD treatment.The difficulty of ESD is to expose the submucosa,especially in difficult sites and lesions with severe fibrosis.Adequate submucosal exposure is the most critical technology to reduce complications and improving efficiency.Here we report a novel entire traction method to facilitate safe and efficient ESD.

Triangular pulley traction facilitates endoscopic full-thickness resection of exogenous gastric tumor in the fornix of the stomach.

A 65-year-old woman was diagnosed with an exogenous submucosal tumor located in the fornix of the stomach, on the basis of the endoscopic ultrasound and enhanced CT findings. She refused surgery and referred for EFTR. It is difficult to perform EFTR at the gastric fornix and suture the large surgical defect. Therefore, we created technique of triangular pulley traction combined with pre-closure.

Entire traction using clip-and-nylon ring to facilitate endoscopic submucosal dissection of a laterally spreading tumor with fibrosis in the rectum.

A 78-year-old woman with hematochezia underwent a colonoscopy and found a 2 × 2-cm laterally spreading tumor (LST) in the rectum, 3 cm from the anus. Because of the risk related to anus preservation and the potential operative trauma, the patient refused surgery and was referred for ESD treatment. Here, we applied a novel entire traction method to deal with this subset of tumors.

CYFIP2 serves as a prognostic biomarker and correlates with tumor immune microenvironment in human cancers.

BACKGROUND: The mechanisms whereby CYFIP2 acts in tumor development and drives immune infiltration have been poorly explored. Thus, this study aimed to identifying the role of CYFIP2 in tumors and immune response. METHODS: In this study, we first explored expression patterns, diagnostic role and prognostic value of CYFIP2 in cancers, particularly in lung adenocarcinoma (LUAD). Then, we performed functional enrichment, genetic alterations, DNA methylation analysis, and immune cell infiltration analysis of CYFIP2 to uncover its potential mechanisms involved in immune microenvironment. RESULTS: We found that CYFIP2 significantly differentially expressed in different tumors including LUAD compared with normal tissues. Furthermore, CYFIP2 was found to be significantly correlated with clinical parameters in LUAD. According to the diagnostic and survival analysis, CYFIP2 may be employed as a potential diagnostic and prognostic biomarker. Moreover, genetic alterations revealed that mutation of CYFIP2 was the main types of alterations in different cancers. DNA methylation analysis indicated that CYFIP2 mRNA expression correlated with hypomethylation. Afterwards, functional enrichment analysis uncovered that CYFIP2 was involved in tumor-associated and immune-related pathways. Immune infiltration analysis indicated that CYFIP2 was significantly correlated with immune cells infiltration. In particular, CYFIP2 was strongly linked with immune microenvironment scores. Additionally, CYFIP2 exhibited a significant relationship with immune regulators and immune-related genes including chemokines, chemokines receptors, and MHC genes. CONCLUSION: Our results suggested that CYFIP2 may serve as a prognostic cancer biomarker for determining prognosis and might be a promising therapeutic strategy for tumor immunotherapy.

Intestinal topical lidocaine spray improves the efficacy and safety of endoscopic sigmoid polypectomy.

BACKGROUND AND AIMS: Endoscopic polypectomy can prevent colorectal cancer. Adequate surgical field visualization is crucial to complete resection. To prevent visual field loss caused by intestinal peristalsis, we investigated the efficacy and safety of topical lidocaine spraying during the endoscopic sigmoid polypectomy (ESP). METHODS: Retrospective analysis was performed on 100 ESP patients admitted from July 2021 to October 2021, among which 50 patients received lidocaine (case group) and other 50 patients received normal saline (control group). Lidocaine or saline was sprayed on the colonic mucosa within 5 cm above and below the polyps before polypectomy. The en-bloc resection rate (EBRR) and complete resection rate (CRR) were primarily evaluated. Secondary outcomes included EBRR for polyps located in the 5-11 o'clock position, sigmoid colon peristalsis frequency, degree of exposure to the surgical field, operative times, and adverse events. RESULTS: There were no significant differences in the basic demographic characteristics between the two groups. EBRR and CRR in the case group were 72.9% and 95.8%, and in the control group were 53.3% and 91.1%, respectively. The EBRR of sigmoid polyps located at the 5-11 o'clock positions was significantly higher in the case group (82.8%) than in the control group (56.7%) (P = 0.03). Sigmoid colonic peristalsis was significantly inhibited after lidocaine spraying (P < 0.01). There was no statistical difference in the operative times and adverse event rates between the two groups. CONCLUSION: Topical spraying lidocaine around polyps can safely and effectively reduce intestinal peristalsis, thus improving the EBRR of sigmoid polypectomy.