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Prognostic tests using expression profiles of several dozen genes help provide treatment choices for prostate cancer (PCa). However, these tests require improvement to meet the clinical need for resolving overtreatment, which continues to be a pervasive problem in PCa management. Genomic selection (GS) methodology, which utilizes whole-genome markers to predict agronomic traits, was adopted in this study for PCa prognosis. We leveraged The Cancer Genome Atlas (TCGA) database to evaluate the prediction performance of six GS methods and seven omics data combinations, which showed that the Best Linear Unbiased Prediction (BLUP) model outperformed the other methods regarding predictability and computational efficiency. Leveraging the BLUP-HAT method, an accelerated version of BLUP, we demonstrated that using expression data of a large number of disease-relevant genes and with an integration of other omics data (i.e. miRNAs) significantly increased outcome predictability when compared with panels consisting of a small number of genes. Finally, we developed a novel stepwise forward selection BLUP-HAT method to facilitate searching multiomics data for predictor variables with prognostic potential. The new method was applied to the TCGA data to derive mRNA and miRNA expression signatures for predicting relapse-free survival of PCa, which were validated in six independent cohorts. This is a transdisciplinary adoption of the highly efficient BLUP-HAT method and its derived algorithms to analyze multiomics data for PCa prognosis. The results demonstrated the efficacy and robustness of the new methodology in developing prognostic models in PCa, suggesting a potential utility in managing other types of cancer. [ABSTRACT FROM AUTHOR]

The underlying mechanism by which anti-VEGF agents prolong cancer patient survival is poorly understood. We show that in a mouse tumor model, VEGF systemically impairs functions of multiple organs including those in the hematopoietic and endocrine systems, leading to early death. Anti-VEGF antibody, bevacizumab, and anti-VEGF receptor 2 (VEGFR-2), but not anti-VEGFR-1, reversed VEGF-induced cancer- associated systemic syndrome (CASS) and prevented death in tumor- bearing mice. Surprisingly, VEGFR2 blockage improved survival by rescuing mice from CASS without significantly compromising tumor growth, suggesting that "off-tumor" VEGF targets are more sensitive than the tumor vasculature to anti-VEGF drugs. Similarly, VEGF-induced CASS occurred in a spontaneous breast cancer mouse model overexpressing neu. Clinically, VEGF expression and CASS severity positively correlated in various human cancers. These findings define novel therapeutic targets of anti-VEGF agents and provide mechanistic insights into the action of this new class of clinically available anti-VEGF cancer drugs [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is a prevalent malignant tumor in men worldwide. Kinases play a key role in the development of multiple tumors. Nevertheless, the role of kinases in PCa remains largely unclear., Methods: A kinase-related gene signature was constructed by LASSO Cox regression analysis using the TCGA_PRAD cohort. The diagnostic and prognostic values of the signature were then evaulated. Furthermore, a loss-of-function assay was carried out to explore the function of NEK5 in PCa., Results: A signature of 13 kinase-related genes (NEK5, FRK, STK39, STYK1, IGF1R, RPS6KC1, TTK, CDK1, NEK2, PTK6, DAPK1, MELK and EPHA10) was constructed. The PCa patients presenting a high-risk score according to the signature demonstrated poorer disease-free survival compared to those with a low score. Additionally, TMB was found to be remarkably increased in patients categorized as high-risk relative to low-risk patients. Moreover, the 13-gene signature may also have good predictive value for PCa diagnosis. Furthermore, NEK5 expression was remarkably elevated in PCa tissues relative to benign tissues. NEK5 deficiency significantly inhibited PCa cell growth and suppressed mitochondrial OXPHOS., Conclusion: The 13-gene signature constructed in this study may exhibit good performance in PCa diagnosis and prognosis evaluation. We identified the oncogenic role of NEK5 in PCa. NEK5 may serve as a therapeutic target for treatting PCa., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background/aim: Solute carrier (SLC) family 15 member 2 (SLC15A2) is an integral member of the SLC family that plays a pivotal role in numerous biological processes, including the regulation of cellular signaling pathways. However, its role in prostate cancer (PCa) remains inadequately elucidated. This study aims to investigate the prognostic significance of SLC15A2 in PCa., Materials and Methods: We evaluated the expression levels and prognostic significance of SLC15A2 in multicenter cohorts of PCa through differential expression analysis, survival analysis, and Cox regression. These findings were validated through immunohistochemistry and in vitro experiments. Gene set enrichment analysis, mutation analysis, and methylation analysis were used to investigate the potential biological functions of SLC15A2. Finally, drug target prediction analysis was conducted to identify small molecule therapeutic agents specifically targeting SLC15A2 in PCa., Results: The expression level of SLC15A2 in PCa tissues was significantly lower compared to benign tissues, and reduced expression of SLC15A2 was often associated with early biochemical recurrence (BCR) and decreased overall survival in PCa patients. Moreover, results from in vitro experiments indicated that knockdown of SLC15A2 markedly enhanced the proliferation and migratory capacity of PCa cells. Enrichment analysis indicated that SLC15A2 predominantly activates pathways related to cell proliferation, adhesion, and lipid metabolism while inhibiting pathways associated with protein synthesis, degradation, RNA metabolism, and energy metabolism. Notably, the frequency of TP53 mutations and 8q24.21 copy number variations was significantly higher in the low SLC15A2 expression group. DNA hypermethylation of SLC15A2 at gene body linked to downregulation of SLC15A2 in PCa. Finally, analysis with the Connectivity Map database identified several promising small molecule drugs for PCa treatment, including rucaparib., Conclusion: Our findings suggest that SLC15A2 serves as a promising prognostic biomarker in PCa, enabling accurate risk stratification for BCR. This insight may contribute to the advancement of personalized treatment strategies for PCa., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Adrenocortical carcinoma (ACC) afflicts both pediatric and adult populations and is characterized by dismal prognosis and elevated mortality. Given the inconsistent therapeutic benefits and significant side effects associated with the conventional chemotherapy agent, mitotane, and the nascent stage of immunotherapy and targeted treatments, there is an urgent need to identify novel prognostic biomarkers and therapeutic targets in ACC., Methods: Utilizing multi-omic datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we employed Weighted Gene Co-expression Network Analysis (WGCNA), Cox regression, Receiver Operating Characteristic (ROC) curves, and survival analyses to sift for potential prognostic biomarkers. We subsequently validated these findings through immunohistochemistry and cell assays, and delved into the biological role of KPNA2 in ACC through functional enrichment analysis, mutational landscape, and immune cell infiltration., Results: A total of 77 progression-associated genes with aberrant chromosomal accessibility were discerned within the TCGA-ACC dataset. By integrating ROC and Cox regression from GEO datasets, KPNA2 emerged as an independent risk factor portending poor outcomes in ACC. ATAC-seq analysis revealed attenuated chromatin accessibility of KPNA2 in cases with unfavorable prognosis. Immunohistochemistry corroborated elevated KPNA2 expression, which was linked to enhanced proliferation and invasion. Elevated KPNA2 levels were found to activate oncogenic pathways while simultaneously suppressing immunological responses. Immune infiltration analysis further revealed a decrement in CD8+ T-cell infiltration in KPNA2-high cohorts., Conclusion: This study demonstrates the clinical and biological significance of KPNA2 in ACC and suggests that KPNA2 could serve as a promising biomarker for predicting prognosis and immunotherapeutic responses in pediatric and adult ACC patients.

Background: Renal cell carcinoma (RCC) is a heterogeneous disease. Identifying effective biomarkers is crucial for improving prognostic accuracy and therapy outcomes. This study investigates cell division cycle-associated 3 ( CDCA3 ) as a novel biomarker for prognostic assessment and immunotherapy response in RCC., Methods: This study analyzed multi-omics data from The Cancer Genome Atlas (TCGA) for kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and kidney chromophobe (KICH) subtypes to evaluate CDCA3 expression and its clinical implications. Functional enrichment and immune infiltration analyses were performed using bioinformatics tools gene set enrichment analysis (GSEA) and xCell. The prognostic value of CDCA3 was assessed through Cox regression and Kaplan-Meier survival analysis. Immunohistochemistry (IHC) was employed to confirm CDCA3 expression at the protein level in RCC samples., Results: Higher CDCA3 expression correlated with poor survival outcomes and reduced response to programmed cell death protein 1 (PD-1) blockade therapies. Statistical analysis indicated that CDCA3 was an independent prognostic factor for poor survival in RCC. CDCA3 was consistently overexpressed in RCC tissues compared to normal tissues and was associated with adverse clinical features, including high Th2 cell infiltration and suppression of immune pathways., Conclusions: CDCA3 is a promising biomarker for RCC, offering insights into the tumor's prognosis and potential response to immunotherapy. The strong association between CDCA3 expression and poor therapeutic outcomes suggests that CDCA3 could be targeted in future therapeutic strategies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-233/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Objective: Metabolism, a basic need and biochemical process for cell survival and proliferation, is closely connected with the pathogenesis and progression of prostate cancer., Methods: A four-gene signature construct that includes CKM (CKM), CD38, Enoyl Coenzyme A(EHHADH), and Arginase 2(ARG2) was created by bioinformatics. Finally, hub genes were validated by IHC and in vitro experiments., Results: The results showed the AUCs of the logistic regression and neural networks diagnostic model for the diagnosis of two subtypes were 0.920 and 0.936, respectively. The risk score demonstrated by univariable and multivariable Cox analysis is an independent predictive component of the prognostic signature for DFS. According to immunohistochemical analyses, ARG2 and CD38 expression levels were considerably under-expressed, but CKM and EHHADH expression levels were significantly overexpressed. Furthermore, The expression of ARG2 was significantly down-regulated in the late Gleason score. Finally, we found that ARG2 is lowly expressed in prostate cancer cells. Furthermore, based on the effect of ARG2 on the malignant phenotype of PCa in vitro, we also found that ARG2 may be a tumor suppressor that plays an important role in inhibiting proliferation, migration, and invasion., Conclusions: These findings suggest that ARG2 has been tentatively identified as a new target for research into how PCa develops in metabolism and for the development of innovative targeted treatments.

Given the heterogeneity of tumors, there is an urgent need for accurate prognostic parameters in prostate cancer (PCa) patients. Lipid metabolism (LM) reprogramming and oxidative stress (OS) play a vital role in the progression of PCa. In this work, we identified five LM-OS-related genes (including ACOX2, PPRAGC1A, PTGS1, PTGS2, and HAO1) associated with the biochemical recurrence (BCR) of PCa. Subsequently, a prognostic signature was established based on these five genes. Kaplan-Meier survival estimates, receiver operating characteristic curves, and relationship analysis between risk score and clinical characters were applied to measure the robustness of the signature in an external cohort. A nomogram of risk score combined with clinical characteristics was constructed for clinical application. Functional enrichment analysis suggested that the underlying mechanism related to the signature included the calcium signaling, lipid transport, and cell cycle signaling pathways. Furthermore, WEE1 inhibitor was identified as a potential agent related to the cell cycle for high-risk patients. The mRNA expression and the prognostic value of the five genes were determined, and ACOX2 was identified as the key gene related to the prognostic signature. The protein expression of ACOX2 was measured in a prostate tissue microarray through an immunohistochemistry assay, confirming the bioinformatics results. By constructing the ACOX2-overexpressing PCa cell lines PC-3 and 22Rv1, the biological function of PCa cells was investigated. The cell viability, colony formation, migration, and invasion ability of PCa cell lines overexpressing ACOX2 were hindered. Decreased cellular lipid content and elevated cellular ROS content were observed in ACOX2-overexpressing PCa cell lines with reduced G2/M phases. In conclusion, this work presents the first prognostic signature specifically focused on LM-OS for PCa. ACOX2 could serve as a favorable indicator for the BCR in PCa. Further experiments are required to identify the potential underlying mechanism., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Adrenocortical carcinoma (ACC) is a malignancy with a poor prognosis and high mortality rate. A high tumor mutational burden (TMB) has been found to be associated with poor prognosis in ACC. Thus, exploring ACC biomarkers based on TMB holds significant importance for patient risk stratification. In our research, we utilized weighted gene coexpression network analysis and an assay for transposase-accessible chromatin with high-throughput sequencing to identify genes associated with TMB. Through the comprehensive analysis of various public datasets, Lamin B1 (LMNB1) was identified as a biomarker associated with a high TMB and low chromatin accessibility. Immunohistochemical staining demonstrated high expression of LMNB1 in ACC compared to noncancerous tissues. Functional enrichment analyses revealed that the function of LMNB1 is associated with cell proliferation and division. Furthermore, cell assays suggested that LMNB1 promotes tumor proliferation and invasion. In addition, mutation analysis suggested that the high expression of LMNB1 is associated with TP53 mutations. Additionally, LMNB1 was highly expressed in the vast majority of solid tumors across cancers. In our immune analysis, we discovered that the high expression of LMNB1 might suppress the infiltration of CD8+ T cells in the ACC microenvironment. In summary, LMNB1 is a predictive factor for the poor prognosis of adult and pediatric ACC. Its high expression in ACC is positively associated with high TMB and lower chromatin accessibility, and it promotes ACC cell proliferation and invasion. Therefore, LMNB1 holds promise as a novel biomarker and potential therapeutic target for ACC.

Background: Clear cell renal cell carcinoma (ccRCC) is a malignant disease containing tumor-infiltrating lymphocytes. Reactive oxygen species (ROS) are present in the tumor microenvironment and are strongly associated with cancer development. Nevertheless, the role of ROS-related genes in ccRCC remains unclear., Methods: We describe the expression patterns of ROS-related genes in ccRCC from The Cancer Genome Atlas and their alterations in genetics and transcription. An ROS-related gene signature was constructed and verified in three datasets and immunohistochemical staining (IHC) analysis. The immune characteristics of the two risk groups divided by the signature were clarified. The sensitivity to immunotherapy and targeted therapy was investigated., Results: Our signature was constructed on the basis of glutamate-cysteine ligase modifier subunit (GCLM), interaction protein for cytohesin exchange factors 1 (ICEF1), methionine sulfoxide reductase A (MsrA), and strawberry notch homolog 2 (SBNO2) genes. More importantly, protein expression levels of GCLM, MsrA, and SBNO2 were detected by IHC in our own ccRCC samples. The high-risk group of patients with ccRCC suffered lower overall survival rates. As an independent predictor of prognosis, our signature exhibited a strong association with clinicopathological features. An accurate nomogram for improving the clinical applicability of our signature was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the signature was closely related to immune response, immune activation, and immune pathways. The comprehensive results revealed that the high-risk group was associated with high infiltration of regulatory T cells and CD8+ T cells and more benefited from targeted therapy. In addition, immunotherapy had better therapeutic effects in the high-risk group., Conclusion: Our signature paved the way for assessing prognosis and developing more effective strategies of immunotherapy and targeted therapy in ccRCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Luo, Zhao, Tan, Chen, Liu, Ye, Cai, Deng, Li, He, Zhang and Zhong.)

The circRNAs, a new subclass of non-coding RNAs that are catalyzed by RNA-binding proteins (RBPs), have been reported to be associated with the progression of multiple types of cancer. We previously discovered that heterogeneous nuclear ribonucleoprotein L (HnRNP-L), a multi-functional RBP, is associated with pro-proliferation and anti-apoptosis activities in prostate tumor cells. In this study, we aim to establish the biological relevance of circCSPP1 (a newly discovered signature circRNA in prostate cancer [PCa]) and HnRNP-L to prostate cancer progression. First, we demonstrated that circCSPP1 expression was higher in prostate cancer tissues than in benign tissues and higher in prostate cancer cells than in benign cells. Then, the in vitro gain- and loss-of-function experiments showed that the circCSPP1 expression in prostate cancer cells was regulated by HnRNP-L, and the increased circCSPP1 significantly induced autophagy, which led to an enhanced potential in proliferation, migration, and invasion of prostate cancer cells. These results were consistent with the in vivo experiment where increased or decreased circCSPP1 was associated with higher or slower growth rate in grafted tumors. Finally, we demonstrated the potential competing endogenous RNA network, involving circCSPP1, miR-520h, and early growth response factor 1 ( EGR1 ), in prostate cancer cells, which may play an important role in prostate cancer progression. Our study indicated that the increase in circCSPP1 in prostate cancer, which may be catalyzed by HnRNP-L, can induce cellular autophagy through the circCSPP1-miR-520h- EGR1 axis, leading to the progression of prostate tumor. This newly discovered circRNA biomarker may be used for clinical prognosis of prostate cancer as well as for development of novel therapy plans., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Objective: To compare the expression levels of Defective In Cullin Neddylation 1 Domain Containing 1 oncogene in prostate cancer tissues and normal prostate tissues, to explore its effect on cancerous cells, and to investigate its underlying mechanisms on such cells in vitro., Methods: The cross-sectional study was conducted at Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics from Jan 03,2017 to Nov 05,2018, and comprised prostate tissue samples on which immunohistochemistry was used to detect the expression of Defective In Cullin Neddylation 1 Domain Containing 1 oncogene. Short hairpin ribonucleic acid expression plasmid targeting the oncogene was constructed and transferred into prostate cance cell line DU145. The roles of the oncogene in prostate cancer progression were confirmed in vitro. The expression of vimentin and epithelial cadherin influenced by the oncogene were detected using Western blot. Data was analysed using SPSS 24., Results: Of the 80 samples, 3(3.75%) were normal prostate tissues, 7(8.75%) adjacent normal prostate tissues, 20(25%) hyperplasia, and 50(62.5%) prostate cancer tissues. Defective In Cullin Neddylation 1 Domain Containing 1 oncogene expression in prostate cancerous tissues was significantly associated with high Gleason score (p<0.001), metastasis (p<0.05) and pathological stage (p<0.001). The oncogene was found to be an independent prognostic factor for disease-free survival of prostate cancer patients (p=0.0108). In vitro analysis confirmed the tumour promotive role of the oncogene through cell proliferation, invasion and migration assays. Its expression was closely correlated with aggressive progression and poor prognosis in prostate cancer patients (p<0.05). Vimentin and epithelial cadherin were affected by the oncogene., Conclusions: Defective In Cullin Neddylation 1 Domain Containing 1 oncogene highly expressed in DU145 and the prostate cancer tissues, which correlated with prognosis.

Purpose: To explore the protective effect of glycyrrhizin in rats with nephrotic syndrome (NS) induced by adriamycin (ADR)., Methods: 36 Sprague Dawley (SD) male rats were divided into control, untreated and glycyrrhizin treatment groups. The NS rat model was established by injecting ADR twice in the untreated and in the glycyrrhizin treatment groups. Rats in the glycyrrhizin treatment group were fed glycyrrhizin by intragastric administration for 7 days. Changes in the following indices were observed in the three groups before and 4 weeks after the treatment: 24 h urine protein quantitation (UPr), serum cholesterol (Ch), serum albumin (Alb), blood urea nitrogen (BUN), serum creatinine (sCr), laminin (LN), fibronectin (FN), collagen (Col), transforming growth factor beta1 (TGFbeta1) and connective tissue growth factor (CTGF); histopathology by light and electron microscope. Expression of LN, FN, ColIV, TGFbeta1 and CTGF in the cortex of the kidney were detected by semi-quantitative immunohistochemical analysis. Expression of TGFbeta1 and CTGF in the cortex of the kidney was detected by Fluorescein Based Quantitive RT-PCR. Macrophage infiltration was evaluated by the immunoperoxidase staining., Results: Compared with the control group, 24 h UPr, Ch, BUN and sCr of rats in the untreated group were increased. Glycyrrhizin reduced 24 h Upr, Ch, BUN, sCr, LN, FN, Col, TGFbeta1, CTGF, and mean arterial blood pressure. Pathological changes in the kidney, the expression of LN, FN, Col, TGFbeta1 and CTGF in the cortex of the kidney in the glycyrrhizin treatment group were decreased compared with the untreated group. Glycyrrhizin also suppressed macrophage infiltration in the kidneys of NS rat models., Conclusion: Glycyrrhizin exerts protective effects in rats with NS, reducing the excretion of Upr, Ch, BUN, sCr, and mean arterial blood pressure, and also decreasing expression of LN, FN, Col, TGFbeta1 and CTGF in the kidney. Renal function is improved and the severity of NS is lessened.

Objective: To determine the efficacy and incidence of complications of extracorporeal shock-wave lithotripsy (ESWL) compared with pneumatic ureteroscopic lithotripsy (URSL) in the treatment of lower uretheral calculi., Methods: From August 1997 to June 1999, 210 patients with lower ureteric calculi were treated with ESWL and the other 180 with URSL. The stones were fragmented with pneumatic lithotripter. The outcome was assessed by evacuation, retreatment and complication rates., Results: ESWL for lower ureteric calculi resulted in a stone evacuation rate of 78.1%, compared with 93.3% for URSL (P < 0.05). ESWL had a retreatment rate of 11.9% and a perforation rate of 0, while URSL caused perforation of ureters in 3.3% of patients and a refreatment of 2.2%., Conclusion: For the management of lower ureteric calculi, ESWL provides a non-invasive, simple and safe option, and URSL has a higher stone evacuation rate but causes ureter perforation more frequently than ESWL does. Both ESWL and URSL have their respective advantages. It is recommended, however, that URSL be extensively developed for better treatment efficacy, given that the operator has an adequate technical background.