Neuropilin-2 and Its Transcript Variants Correlate with Clinical Outcome in Bladder Cancer

Förster, Sarah; Givehchi, Maryam; Nitschke, Katja; Mayr, Thomas; Kilian, Kerstin; Dutta, Samikshan; Datta, Kaustubh; Nuhn, Philipp; Popović, Zoran V.; Muders, Michael H.; Erben, Philipp

doi:10.3390/genes12040550

Cited by 7 publications

(8 citation statements)

References 47 publications

(41 reference statements)

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“…Although NRP2 is frequently overexpressed in tumors and associated with poor clinical outcomes, the role of the NRP2 isoforms and their impact on macrophages in the TME remains undefined ( 8 , 34 – 39 ). We examined specimens from 99 breast cancer patients where both primary tumors and metastases underwent ecRNA-seq.…”

Section: Resultsmentioning

confidence: 99%

Isoforms of Neuropilin-2 Denote Unique Tumor-Associated Macrophages in Breast Cancer

Dhupar¹,

Jones²,

Powers³

et al. 2022

Front. Immunol.

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Tumor-associated macrophages (TAMs) exert profound influence over breast cancer progression, promoting immunosuppression, angiogenesis, and metastasis. Neuropilin-2 (NRP2), consisting of the NRP2a and NRP2b isoforms, is a co-receptor for heparin-binding growth factors including VEGF-C and Class 3 Semaphorins. Selective upregulation in response to environmental stimuli and independent signaling pathways endow the NRP2 isoforms with unique functionality, with NRP2b promoting increased Akt signaling via receptor tyrosine kinases including VEGFRs, MET, and PDGFR. Although NRP2 has been shown to regulate macrophage/TAM biology, the role of the individual NRP2a/NRP2b isoforms in TAMs has yet to be evaluated. Using transcriptional profiling and spectral flow cytometry, we show that NRP2 isoform expression was significantly higher in TAMs from murine mammary tumors. NRP2a/NRP2b levels in human breast cancer metastasis were dependent upon the anatomic location of the tumor and significantly correlated with TAM infiltration in both primary and metastatic breast cancers. We define distinct phenotypes of NRP2 isoform-expressing TAMs in mouse models of breast cancer and within malignant pleural effusions from breast cancer patients which were exclusive of neuropilin-1 expression. Genetic depletion of either NRP2 isoform in macrophages resulted in a dramatic reduction of LPS-induced IL-10 production, defects in phagosomal processing of apoptotic breast cancer cells, and increase in cancer cell migration following co-culture. By contrast, depletion of NRP2b, but not NRP2a, inhibited production of IL-6. These results suggest that NRP2 isoforms regulate both shared and unique functionality in macrophages and are associated with distinct TAM subsets in breast cancer.

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Section: Resultsmentioning

confidence: 99%

Isoforms of Neuropilin-2 Denote Unique Tumor-Associated Macrophages in Breast Cancer

Dhupar¹,

Jones²,

Powers³

et al. 2022

Front. Immunol.

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“…Concerning KDR, there are not many published data KDR in PC. Just A. Fraga et al demonstrated that KDR−604 T > C was correlated with protein level, accounting for a potential geneenvironment effect in the activation of hypoxia-driven pathways in PC (Förster et al, 2021). In colorectal cancer, for example, a significant association was found between KDR expression, disease stage and lymph status (Fraga et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…It has been identified as an important prognostic marker for worse clinical outcome especially in patients with high PC risk ( Borkowetz et al, 2020 ). There is scarce data according to PC but in other tumors such as bladder cancer, high messenger RNA expression of NRP2, NRP1, PDGFC , and PDGFD are associated with a more aggressive disease (i.e., a high T stage, positive lymph node status and reduced survival) ( Förster et al, 2021 ). Present data reports similarities as previously described in bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

Role of IGF2 in the Study of Development and Evolution of Prostate Cancer

et al. 2022

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Prostate Cancer (PC) is commonly known as one of the most frequent tumors among males. A significant problem of this tumor is that in early stages most of the cases course as indolent forms, so an active surveillance will anticipate the appearance of aggressive stages. One of the main strategies in medical and biomedical research is to find non-invasive biomarkers for improving monitoring and performing a more precise follow-up of diseases like PC. Here we report the relevant role of IGF2 and miR-93-5p as non-invasive biomarker for PC. This event could improve current medical strategies in PC.

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“…Overexpression of P4HB may promote the progression of malignant tumors, including gastric cancer, renal clear cell carcinoma, and bladder cancer, and the expression of P4HB mRNA possesses a notably high level in advanced pathological T-stage (24). PDGFD messenger RNA expression levels correlate with disease severity (i.e., high T-stage, positive lymph node status, and reduced survival) (25). Rac3 is a GTPase that belongs to the Rho family and is regulated by C3 botulinum toxin.…”

Section: Discussionmentioning

confidence: 99%

A prognostic model for bladder cancer based on cytoskeleton-related genes

Peng

Guo

Yang

et al. 2022

Preprint

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A typical cancerous growth in the urinary tract, bladder cancer (BLCA) has a dismal survival rate and a poor chance of being cured. The main cause of tumor death is tumor metastasis, cell migration is crucial in tumor metastasis, and cell-directed movement requires the involvement of the cytoskeleton, so it is said that the cytoskeleton is tightly related to tumor invasion and metastasis. Nevertheless, the expression of genes associated with the cytoskeleton and their prognostic significance in BLCA remain unknown. Differential expression of 546 genes involved in the cytoskeleton was analyzed in BLCA versus normal bladder tissues. According to the outcomes of this analysis of differentially expressed genes (DEGs), all BLCA cases doing NMF clustering analysis could be classified into two molecular subtypes and were subjected to survival analysis. Using the TCGA dataset to screen out genes with drastically differing expression levels, a cytoskeleton-associated gene prediction model for bladder cancer was constructed, and 11 genes were assigned risk formulae using the least absolute shrinkage and selection operator (LASSO) Cox regression approach. We divided all TCGA cohort patients with BLCA into low-risk groups and high-risk groups categories based on the average risk score in the middle, then analyzed survival data and ROC curves separately for each risk category. An external validation dataset (GSM340668) was used to verify the accuracy of the model. Columnar line plots were created to predict the prognostic outcome of bladder cancer cases. Significant enrichment pathways for cytoskeleton-associated genes in bladder cancer samples were explored by GSEA enrichment analysis. In addition, immune infiltration studies were conducted to help us better understand and observe the degree of bladder cancer immune cell infiltration. An independent prognostic analysis of risk score (RS) was done and proven to be a significant predictor of outcome for bladder cancer. Following this, we looked at the connection between risk score, clinical characteristics, and immune cells, and found that they are all interconnected. In conclusion, cytoskeleton-related genes have an important predictive value for bladder cancer, and the prognostic model we constructed may enable personalized treatment of bladder cancer.

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Neuropilin-2 and Its Transcript Variants Correlate with Clinical Outcome in Bladder Cancer

Cited by 7 publications

References 47 publications

Isoforms of Neuropilin-2 Denote Unique Tumor-Associated Macrophages in Breast Cancer

Isoforms of Neuropilin-2 Denote Unique Tumor-Associated Macrophages in Breast Cancer

Role of IGF2 in the Study of Development and Evolution of Prostate Cancer

A prognostic model for bladder cancer based on cytoskeleton-related genes

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