M6A Classification Combined With Tumor Microenvironment Immune Characteristics Analysis of Bladder Cancer

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Sept. 15, 2021

Studies have shown that N6-methyl adenosine (m6A) plays an important role in cancer progression; however, the underlying mechanism of m6A modification tumor microenvironment (TME) cell infiltration bladder remains unclear. This study aimed to investigate TME cancer. The RNA expression profile and clinical data were obtained from Cancer Genome Atlas Gene Expression Omnibus. We assessed patterns 664 samples based on 20 regulators through unsupervised clustering analysis systematically linked characteristics. ontology gene set variation analyses conducted analyze assessment methylation regulators. Principal component was used construct score quantify genetic alterations highly heterogeneous between normal tissues. Three identified. characteristics consistent with three immune phenotypes, including rejection, inflammation, desert. biological functions different. Cox regression revealed independent signature patient prognosis (HR = 1.198, 95% CI: 1.031-1.390). Patients a low-m6A characterized by increased mutation burden, PD-L1 expression, poorer survival. group also showed significant responses benefits CTLA-4 immunotherapy cohort (p =0.0069). related formation heterogeneity complexity. Assessing pattern individual will improve understanding

Language: Английский

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Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 2: Subtypes and Divergent Differentiation

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(14), P. 7844 - 7844

Published: July 16, 2022

Following several attempts to achieve a molecular stratification of bladder cancer (BC) over the last decade, “consensus” classification has been recently developed provide common base for (BC), encompassing six-cluster scheme with distinct prognostic and predictive characteristics. In order implement subtyping (MS) as risk tool in routine practice, immunohistochemistry (IHC) explored readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results different clinical settings. The second part this review deals pathological features clusters, both conventional divergent urothelial carcinoma, focus on role IHC-based subtyping.

Language: Английский

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What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 2: Clinic–Pathologic Correlations

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 3165 - 3165

Published: Nov. 14, 2021

Many studies have investigated the potential prognostic and predictive role of PD-L1 in prostatic carcinoma (PC). We performed a systematic literature review (PRISMA guidelines) to critically evaluate human tissue-based (immunohistochemistry, molecular analysis, etc.), experimental research (cell lines, mouse models), clinical trials. Despite some controversial results study limitations, expression by tumor cells may be related clinic-pathologic features adverse outcome, including advanced stage (high pT, presence lymph node, distant metastases), positivity surgical margins, high Grade Group, castration resistance. Different rates observed matched primary PCs various metastatic sites same patients. Over-fixation, type/duration decalcification, antibody clone influence immunohistochemical analysis on bone metastases. seemed expressed more frequently castration-resistant (49%) as compared hormone-sensitive (17%). Some series found that was associated with decreased time Treatment ipilimumab, cyclophosphamide/GVAX/degarelix, or degarelix alone increase expression. Correlation overall survival outcomes recurrence were rarely investigated; few analyzed produced conflicting sometimes showed limitations. Further are required. The testing scoring should standardized.

Language: Английский

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Plasmacytoid urothelial carcinoma of the bladder: MRI features and their association with survival

Urologic Oncology Seminars and Original Investigations, Journal Year: 2021, Volume and Issue: 40(3), P. 108.e1 - 108.e10

Published: Nov. 6, 2021

Language: Английский

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What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models)

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(22), P. 12297 - 12297

Published: Nov. 14, 2021

In prostate cancer (PC), the PD-1/PD-L1 axis regulates various signaling pathways and it is influenced by extracellular factors. Pre-clinical experimental studies investigating effects of treatments (alone or combined) may discover how to overcome immunotherapy-resistance in PC-patients. We performed a systematic literature review (PRISMA guidelines) delineate landscape pre-clinical (including cell lines mouse models) that tested with on PD-L1 PC. NF-kB, MEK, JAK, STAT inhibitors human/mouse, primary/metastatic PC-cell variably down-modulated PD-L1-expression, reducing chemoresistance tumor migration. If PC-cells were co-cultured NK, CD8+ T-cells CAR-T cells, immune cytotoxicity increased when was downregulated (opposite for upregulation). models, radiotherapy, CDK4/6-inhibitors, RB deletion induced PD-L1-upregulation, causing PC-immune-evasion. Epigenetic drugs reduce expression. some PC blocking only pathway had limited efficacy growth. Anti-tumor could be combining blockade other approaches (inhibitors tyrosine kinase, PI3K/mTOR JAK/STAT3 pathways, p300/CBP; anti-RANKL and/or anti-CTLA-4 antibodies; cytokines; nitroxoline; DNA/cell vaccines; radiotherapy/Radium-223).

Language: Английский

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Primary Diffuse Large B-Cell Lymphoma of the Urinary Bladder: Update on a Rare Disease and Potential Diagnostic Pitfalls

Current Oncology, Journal Year: 2022, Volume and Issue: 29(2), P. 956 - 968

Published: Feb. 10, 2022

Diffuse large B-cell lymphoma (DLBCL) represents the most frequent type of non-Hodgkin lymphoma. Globally, DLBCL is an aggressive disease, requiring accurate diagnosis and prompt treatment. The often made on biopsy samples a nodal mass, however, approximately 40% cases arise at extranodal sites. common site gastrointestinal tract, however any area may be primarily involved. Primary urinary bladder only 0.2% lymphomas, whereas secondary involvement by systemic more event. Despite being rare, considered to represent predominant primary majority reported in belong DLBCL, NOS group, there are rare EBV-positive NOS. In this review, we summarize current knowledge occurring bladder, with aim increasing clinician pathologist awareness rarely arising bladder. Additionally, focus those entities which should taken into consideration differential diagnosis, highlighting potential diagnostic pitfalls.

Language: Английский

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Analysis of Risk Factors for Recurrence after Transurethral Resection of Bladder Tumor in Patients with Non-Muscle Invasive Bladder Cancer: 2-Year Follow-Up Outcomes

Oncology, Journal Year: 2023, Volume and Issue: 102(4), P. 337 - 342

Published: Aug. 30, 2023

<b><i>Introduction:</i></b> The aim was to investigate the risk factors for recurrence after transurethral resection of bladder tumor (TURBT) in patients with non-muscle invasive cancer (NMIBC) and provide a basis clinical prevention NMIBC. <b><i>Methods:</i></b> From January 2012 December 2020, 592 NMIBC who underwent TURBT attending Second Affiliated Hospital Xi’an Jiaotong University were retrospectively included this study. Patients divided into relapse relapse-free groups according whether occurred within 2 years. Ultimately, 72 group 350 group. Observation indicators age, sex, smoking, underlying disease (hypertension, diabetes, coronary heart disease), two or more lesions, size, hematuria, pathology grading (low, medium, high), staging (Ta, T1), muscular invasion initial pathology, base (sessile, pedunculated), use intravesical drug (pirarubicin, bacillus Calmette-Guerin [BCG], mitomycin, hydroxycamptothecin, gemcitabine). <b><i>Results:</i></b> In study, 2-year rate 17.06%. There significant differences comparison pirarubicin, BCG, mitomycin treatment between (<i>p</i> &lt; 0.05). To avoid missing recurrence, <i>p</i> 0.1 analyzed. results univariate logistic regression analysis showed that BCG (OR = 5.088, 95% CI 1.444–17.73, 0.012), high 0.415, 0.197–0.880, 0.023), T1 stage 2.097, 0.996–4.618, 0.059), 5.029, 1.149–21.77, 0.031), pirarubicin 1.794, 1.079–3.030, 0.024) had significantly higher years TURBT. multivariate 0.4030, 0.1702–0.8426, 0.0241), 1.961, 1.159–3.348, 0.0125), 6.201, 1.275–29.73, 0.0190) <b><i>Conclusion:</i></b> Our study highlights importance postoperative surveillance individualized findings show grading, treatment, are independent However, caution is warranted when interpreting our due small sample size need further research confirm negative impact on rates.

Language: Английский

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What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(22), P. 12314 - 12314

Published: Nov. 15, 2021

Epigenetic alterations (including DNA methylation or miRNAs) influence oncogene/oncosuppressor gene expression without changing the sequence. Prostate cancer (PC) displays a complex genetic and epigenetic regulation of cell-growth pathways tumor progression. We performed systematic literature review (following PRISMA guidelines) focused on PD-L1 in PC. In PC cell lines, CpG island CD274 promoter negatively regulated expression. Histone modifiers also transcription rate: deletion silencing histone MLL3/MML1 can positively regulate drugs (EDs) may be promising reprogramming cells, reversing modifications, immune evasion. EDs promoting chromatin-inactive transcriptional state (such as bromodomain p300/CBP inhibitors) downregulated PD-L1, while favoring chromatin-active (i.e., deacetylase increased miRNAs at post-transcriptional level. miR-195/miR-16 were associated with correlated to longer biochemical recurrence-free survival; they enhanced radiotherapy efficacy lines. miR-197 miR-200a-c mRNA levels inversely large series. miR-570, miR-34a miR-513 involved regulation.

Language: Английский

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Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic lncRNA Signature in Bladder Cancer

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Aug. 2, 2021

Long non-coding RNAs (lncRNAs) act as competing endogenous (ceRNAs) to regulate mRNA expression through sponging microRNA in tumorigenesis and progression. However, following the discovery of new RNA interaction, differentially expressed ceRNA regulatory network are required update. Our study comprehensively analyzed corresponding thus constructed a potentially predictive tool for prognosis. “DESeq2” was used perform differential analysis. Two hundred six (DE) lncRNAs, 222 DE miRNAs, 2,463 mRNAs were found this study. The lncRNA-mRNA interactions miRcode database miRNA-mRNA starBase, miRcode, mirTarBase databases searched, (ceRNA) with 186 nodes 836 subsequently constructed. Aberrant patterns lncRNA NR2F1-AS1 AC010168.2 evaluated two datasets (GSE89006, GSE31684), real-time polymerase chain reaction also performed validate pattern. Furthermore, we that these lncRNAs independent prognostic biomarkers generate signature by univariate multivariate Cox analyses. According signature, patients high-risk group associated poor prognosis validated an external dataset. A novel genomic-clinicopathologic nomogram improve prediction bladder cancer further plotted calibrated. deepens understanding provides easy-to-do genomic-clinicopathological predict cancer.

Language: Английский

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What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 7: PD-L1 Expression in Liquid Biopsy

Journal of Personalized Medicine, Journal Year: 2021, Volume and Issue: 11(12), P. 1312 - 1312

Published: Dec. 6, 2021

Liquid biopsy is an accessible, non-invasive diagnostic tool for advanced prostate cancer (PC) patients, potentially representing a real-time monitoring test tumor evolution and response to treatment through the analysis of circulating cells (CTCs) exosomes. We performed systematic literature review (PRISMA guidelines) describe current knowledge about PD-L1 expression in liquid biopsies PC patients: 101/159 (64%) cases revealed variable number PD-L1+ CTCs. Outcome correlations should be investigated larger series. Nuclear by CTCs was occasionally associated with worse prognosis. Treatment (abiraterone, enzalutamide, radiotherapy, checkpoint-inhibitors) influenced CTC levels. Discordance status detected between primary vs. metastatic tissue corresponding tissues. also released soluble exosomes, which could inhibit T cell function, causing immune evasion. PC-CTC genomic profiling may better characterize ongoing aggressive forms compared evaluation on biopsies/prostatectomy specimens (sometimes sampled long time before recurrence/progression). Myeloid-derived suppressor dendritic (DCs), have immune-suppressive effects microenvironment, been found patients circulation, sometimes expressing PD-L1. Occasionally, their levels correlated clinical outcome. Enzalutamide-progressing castration-resistant increased PD-1+ PD-L1/2+ DCs.

Language: Английский

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