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Abstract Background Evidence suggests that the circadian clock (CIC) is among the important factors for tumorigenesis. We aimed to provide new insights into CIC-mediated molecular subtypes and gene prognostic indexes for prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). Methods PCa data from TCGA was analyzed to identify differentially expressed genes (DEGs) with significant fold changes and p-values. A prognostic index called CIC-related gene prognostic index (CICGPI) was developed through clustering methods and survival analysis and validated on multiple data sets. The diagnostic accuracy of CICGPI for resistance to chemotherapy and radiotherapy was confirmed. Additionally, the interaction between tumor immune environment and CICGPI score was explored, along with their correlation with prognosis. Results TOP2A, APOE, and ALDH2 were used to classify the PCa patients into two subtypes. Cluster 2 had a higher risk of biochemical recurrence (BCR) than cluster 1 for PCa patients undergoing RP or RT. A CIC-related gene prognostic index (CICGPI) was constructed using the above three genes for PCa patents in the TCGA database. The CICGPI score showed good prognostic value in the TCGA database and was externally confirmed by PCa patients in GSE116918, MSKCC2010 and GSE46602. In addition, the CICGPI score had a certain and high diagnostic accuracy for tumor chemoresistance (AUC: 0.781) and radioresistance (AUC: 0.988). For gene set variation analysis, we observed that both beta alanine metabolism and limonene and pinene degradation were upregulated in cluster 1 for PCa patients undergoing RP or RT. For PCa patients undergoing RP, cell cycle, homologous recombination, mismatch repair, and DNA replication were upregulated in cluster 2. A strongly positive relationship between cancer-related fibroblasts and CICGPI score was observed in PCa patients undergoing RP or RT. Moreover, a high density of CAFs was highly closely associated with poorer BCR-free survival of PCa patients. Conclusions In this study, we established CIC-related immunological prognostic index and molecular subtypes, which might be useful for the clinical practice.

Abstract Drug resistance remains a significant challenge in cancer treatment. Recently, the interactions among various cell types within the tumor microenvironment (TME) have deepened our understanding of the mechanisms behind treatment resistance. Therefore, this review aims to synthesize current research focusing on infiltrating cells and drug resistance suggesting that targeting the TME could be a viable strategy to combat this issue. Numerous factors, including inflammation, metabolism, senescence, hypoxia, and angiogenesis, contribute to drug resistance could be a viable strategy to combat this issue. Overexpression of STAT3 is commonly associated with drug-resistant cancer cells or stromal cells. Current research often generalizes the impact of stromal cells on resistance, lacking specificity and statistical robustness. Thus, future research should take notice of this issue and aim to provide high-quality evidence. Despite the existing limitations, targeting the TME to overcome therapy resistance hold promising and valuable potential.

Abstract Telemedicine has gained tremendous development during the COVID‐19 pandemic. With deblocking and opening, telemedicine accelerates the evolvution of the medical “snack community” and undermines the perception of medical students and staff, which promotes the incidence of psychosocial‐related disorders. Moreover, the inconsistent telemedicine adaptability between medical workers and patients aggravates the doctor–patient conflict due to the aging population and COVID‐19 squeal. Telemedicine is colliding with the national healthcare system, whose synchronization with conventional medical service is crucial to coordinate the relationship among medical payment, patient privacy and qualifications of clinicians. This study puts more emphasis on the double‐edged sword role of telemedicine in clinical practice and medical education during the COVID‐19 pandemic and beyond. Overall, while telemedicine has demonstrated its utility in health care throughout the COVID pandemic, it is pretty critical to continue evaluating the efficacy and limitations of telemedicine in order to maintain equal access to medical service and high‐quality medical education. A new concept as telemedicine‐medical “snack community”‐PHS ecosystem, where the psychological health education system and partners healthcare system with enough bandwidth, especially 5G technology, could optimize the effect of telemedicine on medical practice and education, is proposed.

Bladder cancer stands as a prevalent global malignancy, exhibiting notable sex-based variations in both incidence and prognosis. Despite substantial strides in therapeutic approaches, the formidable challenge of drug resistance persists. The genomic landscape of bladder cancer, characterized by intricate clonal heterogeneity, emerges as a pivotal determinant in fostering this resistance. Clonal evolution, encapsulating the dynamic transformations within subpopulations of tumor cells over time, is implicated in the emergence of drug-resistant traits. Within this review, we illuminate contemporary insights into the role of clonal evolution in bladder cancer, elucidating its influence as a driver in tumor initiation, disease progression, and the formidable obstacle of therapy resistance.

Background: Recently, numerous studies have reported the interaction between senescence and oxidative stress in cancer. However, there is a lack of a comprehensive understanding of the precise mechanisms involved. Aim: Therefore, our review aims to summarize the current findings and elucidate by presenting specific mechanisms that encompass functional pathways, target genes, and related aspects. Methods: Pubmed and Web of Science databases were retrieved to search studies about the interaction between senescence and oxidative stress in cancer. Relevant publications in the reference list of enrolled studies were also checked. Results: In carcinogenesis, oxidative stress-induced cellular senescence acts as a barrier against the transformation of stimulated cells into cancer cells. However, the senescence-associated secretory phenotype (SASP) is positively linked to tumorigenesis. In the cancer progression stage, targeting specific genes or pathways that promote oxidative stress-induced cellular senescence can suppress cancer progression. In terms of treatment, many current clinical therapies combine with novel drugs to overcome resistance and reduce side effects by attenuating oxidative stress-induced senescence. Notably, emerging drugs control cancer development by enhancing oxidative stress-induced senescence. These studies highlight the complacted effects of the interplay between oxidative stress and senescence at different cancer stages and among distinct cell populations. Future research should focus on characterizing the roles of distinct senescent cell types in various tumor stages and identifying the specific components of SASP. Concludsion: We've summarized the mechanisms of senescence and oxidative stress in cancer and provided illustrative figures to guide future research in this area.

Objective: Based on software engineering principles, we designed and implemented a medical device data dictionary system that aligns with data integration and industry standards to fulfill the data management needs of medical institutions and healthcare professionals. Materials and Methods: Utilizing the web-based framework alongside open-source technologies such as Spring Boot, Spring Security, Apache MyBatis, Vue, and Element UI, along with database technologies such as MySql, MongoDB, and Redis, we analyze the basic elements of medical device data dictionary system and incorporate layered architecture technology, design the system architecture, functional workflows and database model required for the dictionary system, and conduct professional testing and trial evaluation of the system. Results and Analysis: In this study, we constructed a web-based open medical device data dictionary system that supports front-end and back-end operations. Using a ventilator as a sample for non-integrity assessment, the results of the system utility test showed that the system is functionally complete, satisfies the compatibility requirements of mainstream browsers and poses no significant risks or vulnerabilities to system operation. Conclusion: A medical device data dictionary that characterizes life cycle usage attributes based on their structural and functional properties was constructed. It provides a unified and standardized base for the management and analysis of medical device data, and helps realize the interaction and exchange of medical device data between disparate medical information systems.

The Period (PER) gene family is one of the core components of the circadian clock, with substantial correlations between the PER genes and cancers identified in extensive researches. Abnormal mutations in PER genes can influence cell function, metabolic activity, immunity, and therapy responses, thereby promoting the initiation and development of cancers. This ultimately results in unequal cancers progression and prognosis in patients. This leads to variable cancer progression and prognosis among patients. In-depth studies on the interactions between the PER genes and cancers can reveal novel strategies for cancer detection and treatment. In this review, we aim to provide a comprehensive overview of the latest research on the role of the PER gene family in cancer.

Cellular senescence has been considered as a hallmark of aging. In this study, we aimed to establish two novel prognostic subtypes for prostate cancer patients using senescence-related lncRNAs. Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages. Using SNHG1, MIAT and SNHG3, 430 patients in TCGA database were classified into two subtypes associated with biochemical recurrence (BCR)-free survival and subtype 2 was prone to BCR (HR: 19.62, p < 0.001). The similar results were observed in the GSE46602 and GSE116918. For hallmark gene set enrichment, we found that protein secretion and androgen response were highly enriched in subtype 1 and G2M checkpoint was highly enriched in subtype 2. For tumor heterogeneity and stemness, homologous recombination deficiency and tumor mutation burden were significantly higher in subtype 2 than subtype 1. The top ten genes between subtype 2 and subtype 1 were CUBN, DNAH9, PTCHD4, NOD1, ARFGEF1, HRAS, PYHIN1, ARHGEF2, MYOM1 and ITGB6 with statistical significance. In terms of immune checkpoints, only CD47 was significantly higher in subtype 1 than that in subtype 2. For the overall assessment, no significant difference was detected between two subtypes, while B cells score was significantly higher in subtype 1 than subtype 2. Overall, we found two distinct subtypes closely associated with BCR-free survival and androgen response for prostate cancer. These subtypes might facilitate future research in the field of prostate cancer.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the dominant subtype of kidney cancer. Dysregulation of long-chain acyl-CoA synthetase 1 (ACSL1) is strongly implicated in undesirable results in varieties of cancers. Nevertheless, the dysregulation and associated multi-omics characteristics of ACSL1 in ccRCC remain elusive. Methods We probed the mRNA and protein profiles of ACSL1 in RCC using data from the Cancer Genome Atlas, Gene Expression Omnibus, the Human Protein Atlas (HPA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) and verified them in our patient cohort and RCC cell lines. Correlations between ACSL1 expression and clinicopathological features, epigenetic modification and immune microenvironment characteristics were analyzed to reveal the multi-omics profile associated with ACSL1. Results ACSL1 was down-regulated in ccRCC tissues compared to adjacent normal tissues. Lower expression of ACSL1 was linked to unfavorable pathological parameters and prognosis. The dysregulation of ACSL1 was greatly ascribed to CpG island-associated methylation modification. The ACSL1 high-expression subgroup had enriched fatty acid metabolism-related pathways and high expression of ferroptosis-related genes. In contrast, the ACSL1 low-expression subgroup exhibited higher immune and microenvironment scores, elevated expression of immune checkpoints PDCD1, CTLA4, LAG3, and TIGIT, and higher TIDE scores. Using data from the GDSC database, we corroborated that down-regulation of ACSL1 was associated with higher sensitivity towards Erlotinib, Pazopanib, and PI3K-Akt-mTOR-targeted therapeutic strategies. Conclusion Taken together, our findings point to ACSL1 as a biomarker for prognostic prediction of ccRCC, identifying the tumor microenvironment (TME) phenotype, and even contributing to treatment decision-making in ccRCC patients.

Abstract Background Cellular senescence is growing in popularity in cancer. A dual function is played by the senescence-associated secretory phenotype (SASP) that senescent cells produce in the development of pro-inflammatory niches, tissue regeneration or destruction, senescence propagation, and malignant transformation. In this study, we conducted thorough bioinformatic analysis and meta-analysis to discover detrimental and beneficial subtypes and prognostic index for prostate cancer (PCa) patients using the experimentally confirmed SASP genes. Methods We identified differentially expressed and prognosis-related SASP genes and used them to construct two molecular subtypes and risk score. Another two external cohorts were used to confirm the prognostic effect of the above subtypes and risk score and meta-analysis was further conducted. Additionally, functional analysis, tumor stemness and heterogeneity and tumor microenvironment were also evaluated. We completed analyses using software R 3.6.3 and its suitable packages. Meta-analysis was performed by software Stata 14.0. Results Through multivariate Cox regression analysis and consensus clustering analysis, we used VGF, IGFBP3 and ANG to establish detrimental and beneficial subtypes in the TCGA cohort, which was validated through other two independent cohorts. Meta-analysis showed that detrimental SASP group had significantly higher risk of biochemical recurrence (BCR) than beneficial SASP group (HR: 2.48). Moreover, we also constructed and validated risk score based on these genes to better guide clinical practice. DNA repair, MYC target, oxidative phosphorylation, proteasome and ribosome were highly enriched in detrimental SASP group. Detrimental SASP group had significantly higher levels of B cells, CD8+ T cells, homologous recombination deficiency, loss of heterozygosity, microsatellite instability, purity, tumor mutation burden, mRNAsi, differentially methylated probes and epigenetically regulated RNA expression than beneficial SASP group. The top mutation genes between detrimental and beneficial SASP groups were SPOP, FOXA1, KMT2C, APC, BSN, DNAH17, MYH6, EPPK1, ZNF536 and ZC3H13 with statistical significance. Conclusions From perspective of SASP, we found detrimental and beneficial tumor subtypes which were closely associated with BCR-free survival for PCa patients, which might be important for the furture research in the field of PCa.

Abstract Background Prolyl 4-hydroxylase subunit beta (P4HB) has been reported as a suppressor in ferroptosis. However, no known empirical research has focused on exploring relationships between P4HB and prostate cancer (PCa). In this research, we initially examine the function of P4HB in PCa by thorough analysis of numerous databases and proliferation experiment. Methods We analyzed the correlations of P4HB expression with prognosis, clinical features, mutation genes, tumor heterogeneity, stemness, tumor immune microenvironment and PCa cells using multiple databases and in vitro experiment with R 3.6.3 software and its suitable packages. Results P4HB was significantly upregulated in tumor tissues compared to normal tissues and was closely related to biochemical recurrence-free survival. In terms of clinical correlations, we found that higher P4HB expression was significantly related to older age, higher Gleason score, advanced T stage and residual tumor. Surprisingly, P4HB had highly diagnostic accuracy of radiotherapy resistance (AUC 0.938). TGF beta signaling pathway and dorso ventral axis formation were upregulated in the group of low-expression P4HB. For tumor stemness, P4HB expression was positively related to EREG.EXPss and RNAss, but was negatively associated with ENHss and DNAss with statistical significance. For tumor heterogeneity, P4HB expression was positively related to MATH, but was negatively associated with tumor ploidy and microsatellite instability. For the overall assessment of TME, we observed that P4HB expression was negatively associated with all parameters, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score and ESTIMATE score. Spearman analysis showed that P4HB expression was negatively related to TIDE score with statistical significance. In vitro experiment, RT-qPCR and western blot showed that three siRNAs of P4HB were effective on the knockdown of P4HB expression. Furthermore, we observed that the downregulation of P4HB had significant influence on the cell proliferation of six PCa cell lines, including LNCap, C4-2, C4-2B, PC3, DU145 and 22RV1 cells. Conclusions In this study, we found that P4HB might serve as a prognostic biomarker and predict radiotherapy resistance for PCa patients. Downregulation of P4HB expression could inhibit the cell proliferation of PCa cells.

Abstract Background Apolipoprotein F (APOF) has been less studied in cancers. Thus, we aimed to perform a pan-cancer analysis of the oncogenic and immunological effects of APOF on human cancer. Methods A standardized TCGA pan-cancer dataset was downloaded. Differential expression, clinical prognosis, genetic mutations, immune infiltration, epigenetic modifications, tumor stemness and heterogeneity were analyzed. We conducted all analyses through software R (version 3.6.3) and its suitable packages. Results Overall, we found that the common cancers differentially expressed between tumor and normal samples and prognostic-associated were BRCA, PRAD, KIRP, and LIHC in terms of overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). The pan-cancer Spearman analysis showed that the mRNA expression of APOF was negatively correlated with four tumor stemness indexes (DMPss, DNAss, ENHss, and EREG-METHss) with statistical significance for PRAD and was positively correlated for LIHC. In terms of BRCA and PRAD patients, we found negative correlation of APOF with TMB, MSI, neo, HRD and LOH. The mutation frequencies of BRCA and LIHC were 0.3%. APOF expression was negatively correlated with immune infiltration and positively correlated with tumor purity for PRAD patients. The mRNA expression of APOF was negatively associated with most TILs for LIHC, B cells, CD4+ T cells, neutrophils, macrophages and dendritic cells, but was positively associated with CD8+ T cells. Conclusions Our pan-cancer study offered a relatively comprehensive understanding of the roles of APOF on BRCA, PRAD, KIRP, and LIHC.

Abstract Current evidence indicate that cancer-associated fibroblasts (CAFs) play an important role in prostate cancer (PCa) development and progression. In this study, we identified CAF-related molecular subtypes and prognostic index for PCa patients undergoing radical prostatectomy through integrating single-cell and bulk RNA sequencing data. We completed analyses using software R 3.6.3 and its suitable packages. Through single-cell and bulk RNA sequencing analysis, NDRG2, TSPAN1, PTN, APOE, OR51E2, P4HB, STEAP1 and ABCC4 were used to construct molecular subtypes and CAF-related gene prognostic index (CRGPI). These genes could clearly divide the PCa patients into two subtypes in TCGA database and the BCR risk of subtype 1 was 13.27 times higher than that of subtype 2 with statistical significance. Similar results were observed in MSKCC2010 and GSE46602 cohorts. In addtion, the molucular subtypes were the independent risk factor of PCa patients. We orchestrated CRGPI based on the above genes and divided 430 PCa patients in TCGA database into high- and low- risk groups according to the median value of this score. We found that high-risk group had significant higher risk of BCR than low-risk group (HR: 5.45). For functional analysis, protein secretion was highly enriched in subtype 2 while snare interactions in vesicular transport was highly enriched in subtype 1. In terms of tumor heterogeneity and stemness, subtype 1 showd higher levels of TMB than subtype 2. In addition, subtype 1 had significant higher activated dendritic cell score than subtype 2. Based on eight CAF-related genes, we developed two prognostic subtypes and constructed a gene prognostic index, which could predict the prognosis of PCa patients very well.

Background: We aimed to identify two new prognostic subtypes and create a predictive index for prostate cancer (PCa) patients based on ferroptosis database. Methods: The nonnegative matrix factorization approach was used to identify molecular subtypes. We investigate the differences between cluster 1 and cluster 2 in terms of clinical features, functional pathways, tumour stemness, tumour heterogeneity, gene mutation and tumour immune microenvironment score after identifying the two molecular subtypes. Colony formation assay and flow cytometry assay were performed. Results: The stratification of two clusters was closely connected to BCR-free survival using the nonnegative matrix factorization method, which was validated in the other three datasets. Furthermore, multivariate Cox regression analysis revealed that this classification was an independent risk factor for patients with PCa. Ribosome, aminoacyl tRNA production, oxidative phosphorylation, and Parkinson's disease-related pathways were shown to be highly enriched in cluster 1. In comparison to cluster 2, patients in cluster 1 exhibited significantly reduced CD4+ T cells, CD8+ T cells, neutrophils, dendritic cells and tumor immune microenvironment scores. Only HHLA2 was more abundant in cluster 1. Moreover, we found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of C4-2B and DU145 cell lines. Conclusions: We discovered two new prognostic subtypes associated with immunological dysfunction in PCa patients based on ferroptosis-related genes and found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of PCa cell lines.

Abstract Background Prostate cancer (PCa) is usually considered as cold tumor. Malignancy is associated with cell mechanic changes that contribute to extensive cell deformation required for metastatic dissemination. Thus, we established stiff and soft tumor subtypes for PCa patients from perspective of membrane tension. Methods Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages. Results We constructed stiff and soft tumor subtypes using eight membrane tension-related genes through lasso regression and nonnegative matrix factorization analyses. We found that patients in stiff subtype were more prone to biochemical recurrence than those in soft subtype (HR 16.18; p

Abstract Urinary neoplasms refer to malignant tumours occurring in any part of the urinary system, including the kidney, renal pelvis, ureter, bladder, prostate, etc. The worldwide incidence of urinary system tumours has been increasing yearly. Available methods include surgical treatment, radiotherapy, chemotherapy, endocrine therapy, molecular targeted therapy, and immune therapy. In recent years, emerging evidence has demonstrated that cell pyroptosis plays an important role in the occurrence and progression of malignant urinary tumours. Pyroptosis is a new type of cell death that involves inflammatory processes regulated by gasdermins (GSDMs) and is characterized by membrane perforation, cell swelling and cell rupture. Recent studies have shown that pyroptosis can inhibit and promote the development of tumours. This manuscript reviews the role of pyroptosis in the development and progression of prostate cancer, kidney cancer and bladder cancer and introduces the latest research results in these fields to discuss the therapeutic potential of the pyroptosis pathway in urinary malignancies.

Abstract In this study, we established a novel immunologic gene prognostic index (IGPI) to predict metastasis and provided new insights into tumor immune microenvironment (TIME) for PCa patients receiving radical radiotherapy. GBP2 and IGF1 were independent factors associated with metastasis-free survival. IGPI score was calculated based on GBP2 and IGF1 and this score was an independent risk factor for PCa patients undergoing radical radiotherapy. Patients with higher IGPI score were at higher risk of metastasis and biochemical recurrence, which were externally validated in the TCGA database and other GEO datasets. IGPI score had demonstrated moderate diagnostic ability of radiation resistance (AUC: 0.889). This score increased with the augment of Gleason score and T stage, as well as biochemical recurrence. Using EPIC, ESTIMATE and immunophenoscore (IPS) algorithms, cancer associated fibroblasts (CAFs), macrophages, stromal score, and estimate score were significantly higher in patients with metastasis group compared to their counterpart. Besides, for CAFs, macrophages, stromal score, and estimate score, patients with higher scores were at higher risk of metastasis, and the HRs were 3.65, 4.01, 4.27, and 3.78, respectively. IGPI score was highly positively associated with stromal score (coefficient: 0.39), immune score (coefficient: 0.43), estimate score (coefficient: 0.45), CAFs (coefficient: 0.42) and macrophages (coefficient: 0.42), while showing the opposite relationship with tumor purity (coefficient: − 0.45). In conclusion, we found that IGPI based on GBP2 and IGF1 might serve as a biomarker predicting metastasis for PCa patients. Besides, the current data further highlight the importance of CAFs in the metastatic process of PCa.

Abstract Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore that is required for proper chromosomal segregation and cell division. However, little is known regarding the probable mechanism of SKA3, particularly in terms of prostate cancer (PCA) progression. Multiple databases, including TCGA and GTEx, were utilized to examine the expression of SKA3 in PCA patients and to shed light on the clinical significance and potential mechanism of SKA3 in the onset and progression of PCA. The biological function of SKA3 was evaluated in vitro using RT–qPCR and the CCK8 assay. For statistical analysis, the R 3.6.3 software and its associated packages were utilized. SKA3 was shown to be considerably elevated in PCA patients and was linked to a shorter progress free interval (PFI). Furthermore, we discovered that SKA3 mRNA expression was higher in PCA cells than in normal cells, and inhibition of SKA3 could clearly reduce PCA cell proliferation using the CCK8 assay. Finally, SKA3 could be used as a predictive biomarker in PCA patients.

Abstract In this study, we aimed to perform a pan-cancer analysis of leucine zipper protein 2 (LUZP2). A standardized TCGA pan-cancer dataset was downloaded. Differential expression, clinical prognosis, genetic mutations, immune infiltration, epigenetic modifications, tumor stemness and heterogeneity were analyzed. We conducted all analyses through software R 3.6.3 and its suitable packages. Compared to normal samples, we observed that the LUZP2 mRNA expression was significantly upregulated in LGG, PRAD, LUSC and downregulated in KIRC and other eleven cancer species patients. In terms of overall survival, low-expression of LUZP2 was significantly associated with poor prognosis in lower grade glioma (LGG), lung squamous cell carcinoma (LUSC), kidney renal clear cell carcinoma (KIRC) and prostate adenocarcinoma (PRAD). For progression-free survival, we observed that downregulation of LUZP2 was significantly related to LGG, KIRC, LUSC, and PRAD. Our results observed negative correlations of the stemness of LGG and PRAD with the mRNA expression of LUZP2, whose downregulation was closely associated with poor prognosis. The mutation frequencies of LGG, PRAD, KIRC, and LUSC were 0.4%, 0.4%, 0.3%, and 2.1%, respectively. We detected that the LUZP2 level was negatively associated with TILs in most cancers, including LGG, LUSC, PRAD, and KIRC, while the LUZP2 methylation showed the opposite results. In conclusion, the results of our initial pan-cancer investigation provided a somewhat thorough understanding of the functions of LUZP2 on KIRC, LGG, PRAD, and LUSC.

Abstract Background Senescent cells have been identified in the aging prostate, and the senescence-associated secretory phenotype might be linked to prostate cancer (PCa). Thus, we established a cellular senescence-related gene prognostic index (CSGPI) to predict metastasis and radioresistance in PCa. Methods We used Lasso and Cox regression analysis to establish the CSGPI. Clinical correlation, external validation, functional enrichment analysis, drug and cell line analysis, and tumor immune environment analysis were conducted. All analyses were conducted with R version 3.6.3 and its suitable packages. Results We used ALCAM and ALDH2 to establish the CSGPI risk score. High-risk patients experienced a higher risk of metastasis than their counterparts (HR: 10.37, 95% CI 4.50–23.93, p

Background: Endothelial cells in the tumor microenvironment play an important role in the development of kidney renal clear cell carcinoma (KIRC). We wanted to further identify the function of endothelial cells in KIRC patients by integrating single-cell and bulk RNA sequencing data.Methods: Online databases provide the original data of this study. An endothelial-related prognostic index (ERPI) was constructed and validated by R version 3.6.3 and relative packages.Results: The ERPI consisted of three genes (CCND1, MALL, and VWF). Patients with high ERPI scores were significantly correlated with worse prognosis than those with low ERPI scores in the TCGA training group, TCGA test group, and GSE29609 group. A positive correlation was identified between the ERPI score and poor clinical features. The results of functional analysis indicated that ERPI was significantly associated with immune-related activities. We suggested that patients with high ERPI scores were more likely to benefit from immunotherapy based on the results of immune checkpoints, tumor microenvironment, stemness index, and TCIA, while patients with low ERPI scores were sensitive to gemcitabine, docetaxel, paclitaxel, axitinib, pazopanib, sorafenib, and temsirolimus according to the results of the “pRRophetic” algorithm. Therefore, this ERPI may help doctors choose the optimal treatment for patients with KIRC.Conclusion: By integrating single-cell and bulk RNA sequencing data from KIRC patients, we successfully identified the key genes from the perspective of endothelial cells in the tumor microenvironment and constructed ERPIs that had positive implications in precision medicine.

BackgroundAs a ferroptosis-related gene, the polymorphism of zinc finger protein 419 (ZNF419) at the splice donor site may generate renal cell carcinoma-associated novel minor histocompatibility antigen ZAPHIR. However, the role of ZNF419 in prognosis and immunology in human tumors remains largely unknown. This study aimed to visualize the prognostic landscape of ZNF419 at pan-cancer level and explore the relationship between ZNF419 expression and the tumor immune microenvironment.MethodPan-cancer and mutation data were downloaded from TCGA databases and analyzed through R (version 3.6.4) and its suitable packages. Differential ZNF419 expression and prognosis were analyzed. Correlations with ferroptosis-related genes, pathway analysis, tumor stemness, heterogeneity, mutation landscape, and RNA modifications were also explored. The relationships between ZNF419 expression and tumor immunity were investigated through the TIMER and ESTIMATE methods.ResultZNF419 was differentially expressed between tumor and normal samples and was associated with overall survival, disease-specific survival and progression-free interval for STES, KIRC, LIHC, LUSC, PRAD, and BLCA. We found the interaction between ZNF419 and FANCD2 might involve in ferroptosis in pan-cancer level. In addition, the mutation frequencies of STES, KIRC, LIHC, LUSC, PRAD, and BLCA were 1.5%, 0.3%, 0.3%, 1.9%, 0.2%, and 0.7%, respectively. We detected that the expression of ZNF419 was closely correlated with most immune checkpoint genes and immune regulatory genes. Furthermore, we found that the ZNF419 expression level was negatively related to the immune score in the six cancers mentioned above. The expression of ZNF419 was significantly associated with various infiltrating immune cells, such as CD4+ T cells, CD8+ T cells, and macrophages in patients with KIRC, PRAD, and LUSC but was only significantly related to macrophages in BLCA patients.ConclusionZNF419 might serve as a potential prognostic and immunological pan-cancer biomarker, especially for KIRC, LIHC, LUSC, PRAD, and BLCA.

Background: We sought to determine whether leucine zipper protein 2 (LUZP2) could benefit men with prostate cancer (PCa) undergoing radical radiotherapy (RT) or prostatectomy (RP). Methods: Analysis was done on differentiating expression, clinical prognosis, co-expressed genes, immune infiltration, and epigenetic changes. All of our analyses were done using the R software (version 3.6.3) and the appropriate packages. Results: In terms of PCa, tumor samples expressed LUZP2 more than normal samples did. In the TCGA database and GSE116918, we found that LUZP2 was the only independent risk factor for PCa. The shared enriched pathways for patients undergoing RP or RT were cell-cell adhesion, regulation of filopodium assembly, and extracellular matrix containing collagen. With the exception of TNFRSF14, we discovered that LUZP2 was negatively correlated with 21 immune checkpoints in PCa patients receiving RT. We found a significant inverse relationship between LUZP2 expression and the tumor immune environment, which included B cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score, and estimate score, in patients receiving RP or RT. Additionally, tumor purity was positively correlated with LUZP2. We found that the drug bortezomib may be susceptible to the LUZP2. DNA methylation was significantly associated with the mRNA expression of LUZP2 in PCa patients from the TCGA database, and LUZP2 methylation was positively correlated with immune cells. The proliferative activity of various PCa cells, which correlated to different stages of this disease, was also found to be significantly reduced by LUZP2 reduction, according to the results of our experimental work. Conclusions: We proposed a relatively comprehensive understanding of the roles of LUZP2 on PCa from the fresh perspective of senescence.

Background: Cuprotosis is a new form of programmed cell death induced by copper. We explored the correlation of cuprotosis with clear cell renal cell carcinoma (ccRCC) and constructed a cuprotosis-related signature to predict the prognosis of patients with ccRCC.Methods: The clinical and transcriptomic data of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA), cBioPortal, and GEO databases, and cuprotosis-related gene sets were contained in the previous study. A cuprotosis-related signature was developed based on data from TCGA and verified by data from cBioPortal and GEO databases. The immune cell infiltrates and the corresponding signature risk scores were investigated. Two independent cohorts of clinical trials were analyzed to explore the correlation of the signature risk score with immune therapy response.Results: A signature containing six cuprotosis-related genes was identified and can accurately predict the prognosis of ccRCC patients. Patients with downregulated copper-induced programmed death had a worse overall survival (hazard ratio: 1.90, 95% CI: 1.39–2.59, p < 0.001). The higher signature risk score was significantly associated with male gender (p = 0.026), higher tumor stage (p < 0.001), and higher histological grade (p < 0.001). Furthermore, the signature risk score was positively correlated with the infiltration of B cells, CD8+ T cells, NK cells, Tregs, and T cells, whereas it was negatively correlated with eosinophils, mast cells, and neutrophils. However, no correlation between cuprotosis and response to anti-PD-1 therapy was found.Conclusion: We established a cuprotosis signature, which can predict the prognosis of patients with ccRCC. Cuprotosis was significantly correlated with immune cell infiltrates in ccRCC.

Background: Kidney renal clear cell carcinoma (KIRC) is an inflammation-related carcinoma, and inflammation has been recognized as an important factor in inducing carcinogenesis. To further explore the role of inflammation in KIRC, we developed an inflammation-related signature and verified its correlation with the tumor micro-environment.Methods: After the differential inflammation-related prognostic genes were screened by Lasso regression, the inflammation-related signature (IRS) was constructed based on the risk score of multivariate Cox regression. Then, the prognostic value of the IRS was evaluated by Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis and multivariate Cox regression. Gene set variation analysis (GSVA) was applied to screen out enriched signaling pathways. Infiltrated immune cells, tumor mutational burden (TMB) and immune checkpoints were explored by CIBERSORTx and maftool.Results: Four genes (TIMP1, PLAUR, CCL22, and IL15RA) were used to construct the IRS in patients with KIRC. Kaplan-Meier analysis and multivariate Cox regression identified that the IRS could independently predict the prognosis of patients with KIRC in the training and validation groups. The diagnostic value of the nomogram increased from 0.811 to 0.845 after adding the IRS to the multiparameter ROC analysis. The GSVA results indicated that IRS was closely related to primary immunodeficiency and antigen processing and presentation. The immune checkpoint LAG3 was highly expressed in patients with high-risk score (p < 0.05), while CD274 (PD-L1) and HAVCR2 were highly expressed in patients with low-risk score (p < 0.001). There was a significant positive correlation between the high-risk score group and CD8+ T, activated CD4+ memory T, gamma and delta regulatory T and M0 macrophage cells, while the low-risk score group was negatively associated with B memory, plasma, resting CD4+ memory T, activated NK, M1 macrophages and resting mast cells.Conclusion: We found that the IRS might serve as a biomarker to predict the survival of KIRC. Moreover, patients with high or low-risk score might be sensitive to immune drugs at different immune checkpoints.

PurposeOur aim is to demonstrate the optimal number of ureteral stent placements in patients with a ureteral stricture (US) after balloon dilatation (BD).MethodsA retrospective analysis of 213 patients who underwent BD from 2011 to 2019 was conducted. All statistical analyses were completed by software SPSS 25.0.ResultsOf the patients enrolled, 119 were males and 94 were females. The average age was 44.71 years. One month after stent removal, the overall success rate of ureteral stent placement was 76.99%, and the success rates of single, double, and triple stent groups were 81.7%, 70.3%, and 79.3%, respectively. Six months after stent removal, the overall success rate was 61.9%, and the success rates of the three groups were 61.7%, 52.7%, and 74.1%, respectively. Twelve months after stent removal, the overall success rate was 55.9%, and the success rates of the three groups were 51.9%, 48.6%, and 70.7%, respectively. During indwelling of the stents, the proportions of severe bladder irritation symptoms in the three groups were 13.6%, 16.2%, and 20.7%, respectively. Multivariate analysis indicated the length of US and the time and number of ureteral stent placements were independent risk factors of the treatment effect at 6 months and 12 months after stent removal. Patients in the triple stent group had a better prognosis when compared to those in the single or double stent group.ConclusionThe long-term effect of three stents was better than that of single and double stents, but the success rate of treatment reduced gradually over time.

Overproduction of reactive oxygen species (ROS) and superlative lipid peroxidation promote tumorigenesis, and mitochondrial aldehyde dehydrogenase 2 (ALDH2) is associated with the detoxification of ROS-mediated lipid peroxidation-generated reactive aldehydes such as 4-hydroxy-2-nonenal (4-HNE), malondialdehyde, and acrolein due to tobacco smoking. ALDH2 has been demonstrated to be highly associated with the prognosis and chemoradiotherapy sensitivity of many types of cancer, including leukemia, lung cancer, head and neck cancer, esophageal cancer, hepatocellular cancer, pancreatic cancer, and ovarian cancer. In this study, we explored the possible relationship between ALDH2 and urological cancers from the aspects of ferroptosis, epigenetic alterations, proteostasis, mitochondrial dysfunction, and cellular senescence.

BackgroundGiven the age relevance of prostate cancer (PCa) and the role of mitochondrial dysfunction (MIDS) in aging, we orchestrated molecular subtypes and identified key genes for PCa from the perspective of MIDS.MethodsCluster analysis, COX regression analysis, function analysis, and tumor immune environment were conducted. We performed all analyses using software R 3.6.3 and its suitable packages.ResultsCXCL14, SFRP4, and CD38 were eventually identified to classify the PCa patients in The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) dataset into two distinct clusters. Patients in the cluster 2 had shorter BCR-free survival than those in the cluster 1 in terms of both TCGA database and GEO dataset. We divided the patients from the TCGA database and the GEO dataset into high- and low-risk groups according to the median of MIDS-related genetic prognostic index. For patients in the TCGA database, the biochemical recurrence (BCR) risk in high-risk group was 2.34 times higher than that in low-risk group. Similarly, for patients in the GEO dataset, the risk of BCR and metastasis in high-risk group was 2.35 and 3.04 times higher than that in low-risk group, respectively. Cluster 2 was closely associated with advanced T stage and higher Gleason score for patients undergoing radical prostatectomy or radiotherapy. For patients undergoing radical prostatectomy, the number of CD8+ T cells was significantly lower in cluster 2 than in cluster 1, while cluster 2 had significantly higher stromal score than cluster 1. For patients undergoing radical radiotherapy, cluster 2 had significantly higher level of CD8+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score, and estimate score, but showed lower level of tumor purity than cluster 1.ConclusionsWe proposed distinctly prognosis-related molecular subtypes at genetic level and related formula for PCa patients undergoing radical prostatectomy or radiotherapy, mainly to provide a roadmap for precision medicine.

Fatty acid metabolism (FAM) genes are potentially useful for predicting prognosis and immunotherapy response in bladder cancer (BC). To examine this, we constructed a prognostic model and identified key FAM genes in BC. Using transcriptional expression profiles and clinical data of BC patients from public datasets and Changhai (CH) hospital, we built and validated a risk-score model based on 13 prognostic FAM genes. Differential gene expression identified fatty acid synthase (FASN) as central to fatty acid metabolism in BC. FASN was differentially expressed between normal and tumor tissue, and was related to survival. In the CH dataset, FASN independently predicted muscle-invasive BC. FASN differential expression was significantly related to immune-cell infiltration and patients with low FASN expression responded better to immune checkpoint inhibitor (ICI) treatment. SREBF1 was predicted as the most significant transcription factor for FASN. Competing endogenous RNA network analysis suggested that lncRNA AC107027.3 may upregulate FASN by competitively binding miR-27A-3p, thereby regulating the immunotherapy response in BC. Dasatinib and temsirolimus are potential FASN-targeting drugs. Our model efficiently predicted prognosis in BC. FASN is central to fatty acid metabolism, and a potential indicator and regulator of ICI treatment.

Purpose: Our aim was to assess the efficacy and safety of miniaturized percutaneous nephrolithotomy (mPCNL) versus standard PCNL (sPCNL) to provide higher-level evidence. Materials and Methods: Eligible randomized controlled trials were identified from electronic databases. The data analysis was performed by the Cochrane Collaboration's software RevMan 5.3. Results: A total of 1,219 patients from 9 articles published between 2004 and 2019 were included. Compared with those who received sPCNL, patients who received mPCNL experienced a higher stone-free rate (SFR) (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.03–1.99; p=0.03), lower transfusion rates (OR, 0.33; 95% CI, 0.17–0.63; p=0.0007), and lower drops in hemoglobin (mean difference [MD], −0.72; 95% CI, −1.04 to −0.40; p

Background: Ferroptosis is a new type of programmed cell death which has been reported to be involved in the development of various cancers. In this study, we attempted to explore the possible links between ferroptosis and prostate cancer (PCa), and a novel ferroptosis-related gene prognostic index (FGPI) was constructed to predict biochemical recurrence (BCR) and radiation resistance for PCa patients undergoing radical radiotherapy (RRT). Moreover, the tumor immune microenvironment (TME) of PCa was analyzed.Methods: We merged four GEO datasets by removing batch effects. All analyses were conducted with R version 3.6.3 and its suitable packages. Cytoscape 3.8.2 was used to establish a network of transcriptional factor and competing endogenous RNA.Results: We established the FGPI based on ACSL3 and EPAS1. We observed that FGPI was an independent risk factor of BCR for PCa patients (HR: 3.03; 95% CI: 1.68–5.48), consistent with the result of internal validation (HR: 3.44; 95% CI: 1.68–7.05). Furthermore, FGPI showed high ability to identify radiation resistance (AUC: 0.963; 95% CI: 0.882–1.00). LncRNA PART1 was significantly associated with BCR and might modulate the mRNA expression of EPAS1 and ACSL3 through interactions with 60 miRNAs. Gene set enrichment analysis indicated that FGPI was enriched in epithelial–mesenchymal transition, allograft rejection, TGF beta signaling pathway, and ECM receptor interaction. Immune checkpoint and m6A analyses showed that PD-L2, CD96, and METTL14 were differentially expressed between BCR and no BCR groups, among which CD96 was significantly associated with BCR-free survival (HR: 1.79; 95% CI: 1.06–3.03). We observed that cancer-related fibroblasts (CAFs), macrophages, stromal score, immune score, estimate score, and tumor purity were differentially expressed between BCR and no BCR groups and closely related to BCR-free survival (HRs were 2.17, 1.79, 2.20, 1.93, 1.92, and 0.52 for cancer-related fibroblasts, macrophages, stromal score, immune score, estimate score, and tumor purity, respectively). Moreover, cancer-related fibroblasts (coefficient: 0.20), stromal score (coefficient: 0.14), immune score (coefficient: 0.14), estimate score (coefficient: 0.15), and tumor purity (coefficient: −0.15) were significantly related to FGPI, among which higher positive correlation between cancer-related fibroblasts and FGPI was observed.Conclusion: We found that FGPI based on ACSL3 and EPAS1 might be used to predict BCR and radiation resistance for PCa patients. CD96 and PD-L2 might be a possible target for drug action. Besides, we highlighted the importance of immune evasion in the process of BCR.

BackgroundAdrenocortical carcinoma (ACC) is a rare neoplasm with a high recurrence rate. This study aimed to assess the role of surgery in the clinical management of recurrent ACC.MethodsThe PubMed, Embase, Web of Science, and Cochrane Library databases were searched, and the hazard ratios were pooled.ResultsPatients who underwent resection for recurrence had significantly better OS or OS after recurrence than those who received only nonsurgical treatments (HR 0.34, p < 0.001). Prognostic factors were associated with decreased OS after recurrence, including multiple recurrence (HR 3.23, p = 0.001), shorter disease-free interval (HR 2.94, p < 0.001), stage III-IV of the original tumor (HR 6.17, p = 0.001), sex of male (HR 1.35, p = 0.04), and initial non-R0 resection (HR 2.13, p = 0.001). Prolonged OS after recurrence was observed in those who experienced incomplete resection (HR 0.43, 95% CI 0.31–0.52, I2 = 53%) compared with patients who only received nonsurgical treatments. In the reoperated group, patients who underwent complete resection of recurrence had a prolonged OS after recurrence compared with those who underwent incomplete resection (HR 0.23, p = 0.004).ConclusionsWe confirmed the role of reoperation in the clinical management of recurrent ACC. Select patients might benefit from debulking surgery. The preoperative evaluation of the complete resection of the recurrence is the key means to decide whether patients should undergo surgery. Other prognostic factors associated with prolonged OS include single recurrence site, relatively longer disease-free interval, stage I-II of the original tumor, and female sex.

Background: Bladder urothelial carcinoma (BLCA) is the most common type of bladder cancer. In this study, the correlation between the metabolic status and the outcome of patients with BLCA was evaluated using data from the Cancer Genome Atlas and Gene Expression Omnibus datasets.Methods: The clinical and transcriptomic data of patients with BLCA were downloaded from the Cancer Genome Atlas and cBioPortal datasets, and energy metabolism-related gene sets were obtained from the Molecular Signature Database. A consensus clustering algorithm was then conducted to classify the patients into two clusters. Tumor prognosis, clinicopathological features, mutations, functional analysis, ferroptosis status analysis, immune infiltration, immune checkpoint-related gene expression level, chemotherapy resistance, and tumor stem cells were analyzed between clusters. An energy metabolism-related signature was further developed and verified using data from cBioPortal datasets.Results: Two clusters (C1 and C2) were identified using a consensus clustering algorithm based on an energy metabolism-related signature. The patients with subtype C1 had more metabolism-related pathways, different ferroptosis status, higher cancer stem cell scores, higher chemotherapy resistance, and better prognosis. Subtype C2 was characterized by an increased number of advanced BLCA cases and immune-related pathways. Higher immune and stromal scores were also observed for the C2 subtype. A signature containing 16 energy metabolism-related genes was then identified, which can accurately predict the prognosis of patients with BLCA.Conclusion: We found that the energy metabolism-associated subtypes of BLCA are closely related to the immune microenvironment, immune checkpoint-related gene expression, ferroptosis status, CSCs, chemotherapy resistance, prognosis, and progression of BLCA patients. The established energy metabolism-related gene signature was able to predict survival in patients with BLCA.

BackgroundWe aimed to construct and validate an energy metabolism-related gene prognostic index (EMRGPI) to predict biochemical recurrence (BCR) in patients undergoing radical prostatectomy.MethodsWe used Lasso and COX regression analysis to orchestrate the EMRGPI in the TCGA database, and the prognostic value of EMRGPI was further validated externally using the GSE46602. All analyses were conducted with R version 3.6.3 and its suitable packages.ResultsSDC1 and ADH1B were finally used to construct the risk formula. We classified the 430 tumor patients in the TCGA database into two groups, and patients in the high-risk group had a higher risk of BCR than those in the low-risk group (HR: 1.98, 95%CI: 1.18-3.32, p=0.01). Moreover, in the GSE46602, we confirmed that the BCR risk in the high-risk group was 3.86 times higher than that in the low-risk group (95%CI: 1.61-9.24, p=0.001). We found that patients in the high-risk group had significantly higher proportions of residual tumor, older age, and T stage. SDC1 and ADH1B were significantly expressed low in the normal tissues when compared to the tumor tissues, which were opposite at the protein level. The spearman analysis showed that EMRGPI was significantly associated with B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score, and estimate score. In addition, the EMRGPI was positively associated with the 54 immune checkpoints, among which CD80, ADORA2A, CD160, and TNFRSF25 were significantly related to the BCR-free survival of PCa patients undergoing RP.ConclusionsThe EMRGPI established in this study might serve as an independent risk factor for PCa patients undergoing radical prostatectomy.

IntroductionTo compare the survival benefit of nephrectomy with or without lymph node dissection (LND) for non-metastatic, especially for high-risk renal cell carcinoma (RCC) patients by investigating different survival evaluation indicators.Evidence AcquisitionEligible studies were identified until September 2021, through common databases including PubMed, the Cochrane Library, Embase and China National Knowledge Infrastructure (CNKI) on RCC and LND without language restriction. Data analysis was performed through Stata software, version 16.0 (Stata Corp., College Station, TX, USA).Evidence Synthesis22 articles were included in this meta-analysis. For non-metastatic RCC, performing LND comitantly with nephrectomy did not change the overall survival (OS) of patients of all T stages [hazard ratio (HR)=1.10, 95%CI: 0.95-1.27] and also for T2+NxM0 patients (HR=0.88, 95%CI: 0.68-1.14) as well as for T3+NxM0 patients (HR=0.95, 95%CI: 0.61-1.50). At the same time, cumulative meta-analysis has shown that the survival benefit of LND has a significant declining trend since 1979. However, it is worth noting that the operation of LND presented as a risk factor for cancer specific survival (CSS) (HR=1.22, 95%CI: 1.05-1.43).ConclusionsLatest evidence indicated that LND might not be suitable for all non-metastatic RCC patients, especially in the current situation of various non-invasive examinations for judging lymph node metastasis and adjuvant treatments. On the contrary, excess LND could damage the survival of patients.Systematic Review RegistrationThis study is registered as PROSPERO CRD42021271124.

BackgroundWe aimed to establish a novel epithelial-mesenchymal transition (EMT)-related gene prognostic index (EMTGPI) associated with biochemical recurrence (BCR) and drug resistance for prostate cancer (PCa).MethodsWe used Lasso and Cox regression analysis to establish the EMTGPI. All analyses were conducted with R version 3.6.3 and its suitable packages.ResultsWe established the EMTGPI based on SFRP4 and SPP1. Patients in high-risk group had 2.23 times of BCR risk than those in low-risk group (p = 0.003), as well as 2.36 times of metastasis risk (p = 0.053). In external validation, we detected similar diagnostic efficacy and prognostic value in terms of BCR free survival. For drug resistance, we observe moderately diagnostic accuracy of EMTGPI score (AUC: 0.804). We found that PDCD1LG2 (p = 0.04) and CD96 (p = 0.01) expressed higher in BCR patients compared with their counterpart. For TME analysis, we detected that CD8+ T cells and M1 macrophages expressed higher in BCR group. Moreover, stromal score (p = 0.003), immune score (p = 0.01), and estimate score (p = 0.003) were higher in BCR patients. We found that EMTGPI was significantly related to HAVCR2 (r: 0.34), CD96 (r: 0.26), CD47 (r: 0.22), KIR3DL1 (r: −0.21), KLRD1 (r: −0.21), and CD2 (r: 0.21). In addition, we observed that EMTGPI was significantly associated with M1 macrophages (r: 0.6), M2 macrophages (r: −0.33), monocytes (r: −0.18), neutrophils (r: −0.43), CD8+ T cells (r: 0.13), and dendritic cells (r: 0.37). PHA-793887 was the common drug sensitive to SPP1 and SFRP4, and PC3 and DU145 were the common PCa-related cell lines of SPP1, SFRP4, and PHA-793887.ConclusionsWe concluded that the EMTGPI score based on SFRP4 and SPP1 could be used to predict BCR for PCa patients. We confirmed the impact of immune evasion on the BCR process of PCa.

BackgroundCurrently, the impact of the circadian rhythm on the tumorigenesis and progression of prostate cancer (PCA) has yet to be understood. In this study, we first established a novel nomogram to predict PCA progression based on circadian clock (CIC)-related genes and provided insights into the tumor immune microenvironment.MethodsThe TCGA and Genecards databases were used to identify potential candidate genes. Lasso and Cox regression analyses were applied to develop a CIC-related gene signature. The tumor immune microenvironment was evaluated through appropriate statistical methods and the GSCALite database.ResultsTen genes were identified to construct a gene signature to predict progression probability for patients with PCA. Patients with high-risk scores were more prone to progress than those with low-risk scores (hazard ratio (HR): 4.11, 95% CI: 2.66-6.37; risk score cut-off: 1.194). CLOCK, PER (1, 2, 3), CRY2, NPAS2, RORA, and ARNTL showed a higher correlation with anti-oncogenes, while CSNK1D and CSNK1E presented a greater relationship with oncogenes. Overall, patients with higher risk scores showed lower mRNA expression of PER1, PER2, and CRY2 and higher expression of CSNK1E. In general, tumor samples presented higher infiltration levels of macrophages, T cells and myeloid dendritic cells than normal samples. In addition, tumor samples had higher immune scores, lower stroma scores and lower microenvironment scores than normal samples. Notably, patients with higher risk scores were associated with significantly lower levels of neutrophils, NK cells, T helper type 1, and mast cells. There was a positive correlation between the risk score and the tumor mutation burden (TMB) score, and patients with higher TMB scores were more prone to progress than those with lower TMB scores. Likewise, we observed similar results regarding the correlation between the microsatellite instability (MSI) score and the risk score and the impact of the MSI score on the progression-free interval. We observed that anti-oncogenes presented a significantly positive correlation with PD-L1, PD-L2, TIGIT and SIGLEC15, especially PD-L2.ConclusionWe identified ten prognosis-related genes as a promising tool for risk stratification in PCA patients from the fresh perspective of CIC.

Background: The unfolded protein response (UPR) plays a significant role in maintaining protein hemostasis in tumor cells, which are crucial for tumor growth, invasion, and resistance to therapy. This study aimed to develop a UPR-related signature and explore its correlation with immunotherapy and chemotherapy in bladder cancer.Methods: The differentially expressed UPR-related genes were put into Lasso regression to screen out prognostic genes, which constituted the UPR signature, and were incorporated into multivariate Cox regression to generate risk scores. Subsequently, the predictive performance of this signature was estimated by receiver operating characteristic (ROC) curves. The CIBERSORTx, the maftool, and Gene set enrichment analysis (GSEA) were applied to explore infiltrated immune cells, tumor mutational burden (TMB), and enriched signaling pathways in both risk groups, respectively. Moreover, The Cancer Immunome Atlas (TCIA) and Genomics of Drug Sensitivity in Cancer (GDSC) databases were used to predict responses to chemotherapy and immunotherapy.Results: Twelve genes constituted the UPR-related signature. Patients with higher risk scores had worse overall survival (OS) in training and three validation sets. The UPR-related signature was closely correlated with clinicopathologic parameters and could serve as an independent prognostic factor. M0 macrophages showed a significantly infiltrated difference in both risk groups. TMB analysis showed that the risk score in the wild type and mutation type of FGFR3 was significantly different. GSEA indicated that the immune-, extracellular matrix-, replication and repair associated pathways belonged to the high risk group and metabolism-related signal pathways were enriched in the low risk group. Prediction of immunotherapy and chemotherapy revealed that patients in the high risk group might benefit from chemotherapy, but had a worse response to immunotherapy. Finally, we constructed a predictive model with age, stage, and UPR-related risk score, which had a robustly predictive performance and was validated in GEO datasets.Conclusion: We successfully constructed and validated a novel UPR-related signature in bladder cancer, which could robustly predict survival outcomes and closely correlate with the response to immunotherapy and chemotherapy in bladder cancer.

Background: Bladder cancer is the second-ranked tumor of the genitourinary system. Transurethral resection of bladder tumor (TURBT) is currently the most important diagnosis and treatment method for non-muscular invasive bladder cancer (NMIBC). However, due to its high recurrence and progression rate, as well as high cost and inapplicability to some patients, intravesical chemoablation as an alternative to TURBT may be promising for NMIBC patients. However, there are very little data comparing its effectiveness, safety, best effective drug type, dosage selection, and cost with TURBT at present, which deserves further evaluation. The present study was designed in order to discuss which treatment is superior to another between chemoablation and TURBT in patients with NMIBC.Methods and Analysis: Databases including PubMed, MEDLINE, EMBASE, and Cochrane Library databases, as well as Chinese databases including CNKI (China national knowledge infrastructure), Wan Fang database, and Chinese Clinical Trial Registry, from August 1994 to the time when the official submission of this review was published was included in this review and screened by two reviewers (XS and DCF) independently. There were no language limitations. The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data was analyzed using RevMan and Stata software. The primary aims were the clinical effectiveness, including response rate, complete response OS, CSM, recurrence rate, time to recurrent, progression rate, and time to progression, among others. The secondary aims mainly included safety and tolerability, including costs, operation time, hospital stay, bleeding volume, and complications, among others.Study Registration: This study is registered as PROSPERO CRD42021271124.

Conservative treatment is closely associated with renal deterioration for patients with renal staghorn stones. It is well-recognized that percutaneous nephrolithotomy (PCNL) is recommended as the first-line treatment of renal stones larger than 2 cm due to its higher stone clearance and cost-effectiveness when compared with other treatment alternatives, such as shockwave lithotripsy and flexible ureteroscopy (FURS). Besides, our findings indicated that miniaturized PCNL could be served as an alternative to PCNL with a higher stone-free rate and a lower hemorrhage risk. Despite the higher cost-effectiveness of PCNL, the management of staghorn stones are still controversial in some special situations, such as a solitary kidney. Herein, we present a case with complex infectious stones of a right-sided solitary kidney, complaining of persistent pain in the right waist. The rarity of this case is that it is difficult to encounter these cotton-like staghorn stones which are clinically resistant to holmium laser lithotripsy, and the particularity is that the patient with solitary kidney failed to undergo PCNL. We found that the combination of intermittently high-frequency oscillation and flexible ureteroscopy forceps might contribute to treat the complex infectious stones in a patient with solitary kidney. Our surgical experience might be beneficial to such patients undergoing flexible ureteroscopy in clinical practice.

Background: We aimed to explore the role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in prostate cancer (PCa) patients and provide insights into the tumor immune microenvironment (TME) for those patients undergoing radical radiotherapy. Methods: We performed all analyses using R version 3.6.3 and its suitable packages. Cytoscape 3.8.2 was used to establish network of competing endogenous RNAs (ceRNAs). Results: Downregulation of ADLH2 was significantly associated with higher risk of BCR-free survival (HR: 0.40, 95%CI: 0.24–0.68, p = 0.001) and metastasis-free survival (HR: 0.21, 95%CI: 0.09–0.49, p = 0.002). Additionally, ALDH2 repression contributed to significantly shorter BCR-free survival in the TCGA database (HR: 0.55, 95%CI: 0.33–0.93, p = 0.027). For immune checkpoints, patients that expressed a higher level of CD96 had a higher risk of BCR than their counterparts (HR: 1.79, 95%CI: 1.06–3.03, p = 0.032), as well as NRP1 (HR: 2.18, 95%CI: 1.29–3.69, p = 0.005). In terms of the TME parameters, the spearman analysis showed that ALDH was positively associated with B cells (r: 0.13), CD8+ T cells (r: 0.19), neutrophils (r: 0.13), and macrophages (r: 0.17). Patients with higher score of neutrophils (HR: 1.75, 95%CI: 1.03–2.95, p = 0.038), immune score (HR: 1.92, 95%CI: 1.14–3.25, p = 0.017), stromal score (HR: 2.52, 95%CI: 1.49–4.26, p = 0.001), and estimate score (HR: 1.81, 95%CI: 1.07–3.06, p = 0.028) had higher risk of BCR than their counterparts. Our ceRNA network found that PART1 might regulate the expression of ALDH via has-miR-578 and has-miR-6833-3p. Besides, PHA-793887, PI-103, and piperlongumine had better correlations with ALDH2. Conclusions: We found that ALDH2 might serve as a potential biomarker predicting biochemical recurrence for PCa patients.