Identifying genes with prognostic importance could improve cancer treatment. An increasing number of reports suggest the existence of successful strategies based on seemingly "untargetable" transcription factors. In addition to embryogenesis, AP-2 transcription factors are known to play crucial roles in cancer development. Members of this family can be used as prognostic factors in oncological patients, and AP-2α/γ transcription factors were previously investigated in our pan-cancer comparative study using their target genes. The present study investigates tumors that were previously found similar with an emphasis on the possible role of AP-2 factors in specific cancer types. The RData workspace was loaded back to R environment and 3D trajectories were built via Monocle3. The genes that met the requirement of specificity were listed using top_markers(), separately for mutual and unique targets. Furthermore, the candidate genes had to meet the following requirements: correlation with AP-2 factor (through Correlation AnalyzeR) and validated prognostic importance (using GEPIA2 and subsequently KM-plotter or LOGpc). Eventually, the ROC analysis was applied to confirm their predictive value; co-dependence of expression was visualized via BoxPlotR. Some similar tumors were differentiated by AP-2α/γ targets with prognostic value. Requirements were met by only fifteen genes (EMX2, COL7A1, GRIA1, KRT1, KRT14, SLC12A5, SEZ6L, PTPRN, SCG5, DPP6, NTSR1, ARX, COL4A3, PPEF1 and TMEM59L); of these, the last four were excluded based on ROC curves. All the above genes were confronted with the literature, with an emphasis on the possible role played by AP-2 factors in specific cancers. Following ROC analysis, the genes were verified using immunohistochemistry data and progression-related signatures. Staining differences were observed, as well as co-dependence on the expression of e.g. CTNNB1, ERBB2, KRAS, SMAD4, EGFR or MKI67. In conclusion, prognostic value of targets suggested AP-2α/γ as candidates for novel cancer treatment. It was also revealed that AP-2 targets are related to tumor progression and that some mutual target genes could be inversely regulated. 

/pdf/prognostic-significance-of-ap-2a-g-targets-as-cancer-2r12seys.pdf

Prognostic significance of AP-2α/γ targets as cancer therapeutics

Simple Summary This research aims to understand how gene variations, particularly in the methylenetetrahydrofolate reductase gene (MTHFR), influence bladder cancer development. The study conducted a meta-analysis of seven relevant studies to assess the impact of a specific genetic variant, rs1801133, on bladder cancer susceptibility. The findings indicate a significant association between the MTHFR rs1801133 polymorphism and bladder cancer risk, especially in the Asian population. People with the T-allele or TT genotype had a higher likelihood of developing bladder cancer compared to that of those with the C-allele. This research is vital for the scientific community as it enhances our understanding of genetic factors contributing to bladder cancer. The findings may lead to targeted prevention and personalized treatment strategies. Additionally, the systematic review and meta-analysis provide a comprehensive overview of the existing evidence, adding to the knowledge base on bladder cancer genetics. This could inspire further research into the genetic basis of complex diseases like bladder cancer. Abstract The etiology of bladder cancer remains unclear. This study investigates the impact of gene polymorphisms, particularly methylenetetrahydrofolate reductase gene (MTHFR), on bladder cancer susceptibility, focusing on the rs1801133 single-nucleotide polymorphism (SNP). A meta-analysis was conducted after systematically reviewing the MTHFR gene literature, adhering to PRISMA guidelines and registering in PROSPERO (CRD42023423064). Seven studies were included, showing a significant association between the MTHFR C677T (rs1801133) polymorphism and bladder cancer susceptibility. Individuals with the T-allele or TT genotype had a higher likelihood of bladder cancer. In the Asian population, the overall analysis revealed an odds ratio (OR) of 1.15 (95% CI 1.03–1.30; p-value = 0.03) for T-allele versus C-allele and an OR of 1.34 (95% CI 1.04–1.72; p-value = 0.02) for TT genotype versus TC+CC genotype. The CC genotype, however, showed no significant association with bladder cancer. Notably, epigenetic findings displayed low sensitivity but high specificity, indicating reliable identified associations while potentially overlooking some epigenetic factors related to bladder cancer. In conclusion, the MTHFR T-allele and TT genotype were associated with increased bladder cancer risk in the Asian population. These insights into genetic factors influencing bladder cancer susceptibility could inform targeted prevention and treatment strategies. Further research is warranted to validate and expand these findings.

Methylenetetrahydrofolate Reductase C677T (rs1801133) Polymorphism Is Associated with Bladder Cancer in Asian Population: Epigenetic Meta-Analysis as Precision Medicine Approach

/pdf/prognostic-significance-of-ap-2a-g-targets-as-cancer-2uplri0x.pdf

Major fraction of the human genome is transcribed in to the RNA but is not translated in to any specific functional protein. These transcribed but not translated RNA molecules are called as non-coding RNA (ncRNA). There are thousands of different non-coding RNAs present inside the cells, each regulating different cellular pathway/pathways. Over the last few decades non-coding RNAs have been found to be involved in various diseases including cancer. Non-coding RNAs are reported to function both as tumor enhancer and/or tumor suppressor in almost each type of cancer. Urothelial carcinoma of the urinary bladder is the second most common urogenital malignancy in the world. Over the last few decades, non-coding RNAs were demonstrated to be linked with bladder cancer progression by modulating different signalling pathways and cellular processes such as autophagy, metastasis, drug resistance and tumor proliferation. Due to the heterogeneity of bladder cancer cells more in-depth molecular characterization is needed to identify new diagnostic and treatment options. This review emphasizes the current findings on non-coding RNAs and their relationship with various oncological processes such as autophagy, and their applicability to the pathophysiology of bladder cancer. This may offer an understanding of evolving non-coding RNA-targeted diagnostic tools and new therapeutic approaches for bladder cancer management in the future.

Non-coding RNA and autophagy: Finding novel ways to improve the diagnostic management of bladder cancer

We report a 32-year-old male 14 years post-living-related kidney transplant presenting with new-onset hematuria and BK viremia. He was found to have BK virus-associated urothelial carcinoma originating in the renal allograft with locally advanced disease and metastases to multiple sites. He also developed acute T-cell-mediated rejection in the setting of immunosuppression reduction for BK viremia prior to undergoing transplant nephrectomy. Eight months following transplant nephrectomy and immunosuppression cessation, distant metastases persisted with partial response to chemotherapy and immunotherapy. Here, we discuss this unique presentation and compare it with other BK virus-associated allograft carcinomas reported in the literature, in addition to discussing evidence for the role of BK virus in oncogenesis.

https://journals.sagepub.com/doi/pdf/10.1177/10668969231160258

An Unusual Presentation of Metastatic BK Virus-Associated Urothelial Carcinoma Arising in the Allograft, Persisting After Transplant Nephrectomy.

Most of the etiology studies of bladder cancer focus on genetic changes, mainly including mutation and activation of oncogenes, mutation and inactivation of tumor suppressor genes, and rearrangement or heterozygous deletion of chromosomes. Moreover, bladder cancer is highly heterogeneous mainly due to abnormal changes in the genome and proteome of tumor cells. Surgery is the main treatment for bladder cancer, but because the recurrence rate is high after surgery and most of the muscle-invasive bladder cancer acquires distant metastasis. Therefore, there is a need to combine with chemotherapy to consolidate the treatment effect. However, there are differences in chemosensitivity among patients. In this article, we review the up-to-date genomic researches on bladder cancer occurrence, development, metastasis, and chemosensitivity in patients, in order to provide some theoretical support for the diagnosis and treatment strategy for bladder cancer.

/pdf/frontiers-in-bladder-cancer-genomic-research-2hn4svofls.pdf

Frontiers in Bladder Cancer Genomic Research.

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Frontiers in Bladder Cancer Genomic Research.