Screening ANLN and ASPM as bladder urothelial carcinoma-related biomarkers based on weighted gene co-expression network analysis

Introduction: Bladder cancer (BLCA) is one of the most common malignancies in the urinary system with a poor prognosis and high treatment costs. Identifying potential prognostic biomarkers is significant for exploring new therapeutic and predictive targets of BLCA.Methods: In this study, we screened differentially expressed genes using the GSE37815 dataset. We then performed a weighted gene co‐expression network analysis (WGCNA) to identify the genes correlated with the histologic grade and T stage of BLCA using the GSE32548 dataset. Subsequently, Kaplan Meier survival analysis and Cox regression were used to further identify prognosis‐related hub genes using the datasets GSE13507 and TCGA‐BLCA. Moreover, we detected the expression of the hub genes in 35 paired samples, including BLCA and paracancerous tissue, from the Shantou Central Hospital by qRT‐polymerase chain reaction.Results: This study showed that Anillin (ANLN) and Abnormal spindle-like microcephaly-associated gene (ASPM) were prognostic biomarkers for BLCA. High expression of ANLN and ASPM was associated with poor overall survival.The qRT‐PCR results revealed that ANLN and ASPM genes were upregulated in BLCA, and there was a correlation between the expression of ANLN and ASPM in cancer tissues and paracancerous tissue. Additionally, the increasing multiples in the ANLN gene was obvious in high-grade BLCA.Discussion: In summary, this preliminary exploration indicated a correlation between ANLN and ASPM expression. These two genes, serving as the risk factors for BLCA progression, might be promising targets to improve the occurrence and progression of BLCA

A HER2‐targeted Antibody‐Drug Conjugate, RC48‐ADC, Exerted Promising Antitumor Efficacy and Safety with Intravesical Instillation in Preclinical Models of Bladder Cancer

Abstract More than half of non‐muscle‐invasive bladder cancer (NMIBC) patients eventually relapse even if treated with surgery and BCG without optional bladder‐preserving therapy. This study aims to investigate the antitumor activity and safety of a HER2‐targeted antibody‐drug conjugate, RC48‐ADC, intravesical instillation for NMIBC treatment. In this preclinical study, it is revealed that human epidermal growth factor receptor 2 (HER2) expression scores of 1+, 2+, and 3+ are recorded for 16.7%, 56.2%, and 14.6% of NMIBC cases. The antitumor effect of RC48‐ADC is positively correlated with HER2 expression in bladder cancer (BCa) cell lines and organoid models. Furthermore, RC48‐ADC is revealed to exert its antitumor effect by inducing G2/M arrest and caspase‐dependent apoptosis. In an orthotopic BCa model, tumor growth is significantly inhibited by intravesical instillation of RC48‐ADC versus disitamab, monomethyl auristatin E, epirubicin, or phosphate‐buffered saline control. The potential toxicity of intravesical RC48‐ADC is also assessed by dose escalation in normal nude mice and revealed that administration of RC48‐ADC by intravesical instillation is safe within the range of effective therapeutic doses. Taken together, RC48‐ADC demonstrates promising antitumor effects and safety with intravesical administration in multiple preclinical models. These findings provide a rational for clinical trials of intravesical RC48‐ADC in NMIBC patients

Immune regulation and the tumor microenvironment in anti-PD-1/PDL-1 and anti-CTLA-4 therapies for cancer immune evasion: A bibliometric analysis

ABSTRACTThis study aims to conduct a bibliometric analysis, employing visualization tools to examine literature pertaining to tumor immune evasion related to anti-CTLA-4 and anti-PD-1/PD-L1 therapy from 1999 to 2022. A special emphasis is placed on the interplay between tumor microenvironment, signaling pathways, immune cells and immune evasion, with data sourced from the Web of Science core collection (WoSCC). Advanced tools, including VOSviewer, Citespace, and Scimago Graphica, were utilized to analyze various parameters, such as co-authorship/co-citation patterns, regional contributions, journal preferences, keyword co-occurrences, and significant citation bursts. Out of 4778 publications reviewed, there was a marked increase in research focusing on immune evasion, with bladder cancer being notably prominent. Geographically, China, the USA, and Japan were the leading contributors. Prestigious institutions like MD Anderson Cancer Center, Harvard Medical School, Fudan University, and Sun Yat Sen University emerged as major players. Renowned journals in this domain included Frontiers in Immunology, Cancers, and Frontiers in Oncology. Ehen LP and Wang W were identified as prolific authors on this topic, while Topalian SL stood out as one of the most cited. Research current situation is notably pivoting toward challenges like immunotherapy resistance and the intricate signaling pathways driving drug resistance. This bibliometric study seeks to provide a comprehensive overview of past and current research trends, emphasizing the potential role of tumor microenvironment, signaling pathways and immune cells in the context of immune checkpoint inhibitors (ICIs) and tumor immune evasion