Angiogenesis in pancreatic cancer: current research status and clinical implications

Li, Shuo; Xu, Hua; Wu, Chun; Wang, Wen Quan; Jin, Wei; Gao, He; Li, Hao; Zhang, Shi Rong; Xu, Jin; Qi, Zi Hao; Ni, Quan Xing; Lei, Yu

doi:10.1007/s10456-018-9645-2

Cited by 195 publications

(158 citation statements)

References 204 publications

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“…Angiogenesis is crucial for cancer development, and prevention of angiogenesis can be an important means of controlling tumor development. Therefore, prevention of angiogenesis is a valuable treatment for cancer, such as pancreatic cancer . Numerous studies have shown that specific molecules can affect the tumorigenesis, progression, incursion as well as migration of pancreatic cancer by participating in the regulation of JAK/STAT pathway .…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, prevention of angiogenesis is a valuable treatment for cancer, such as pancreatic cancer. [38][39][40] Numerous studies have shown that specific molecules can affect the tumorigenesis, progression, incursion as well as migration of pancreatic cancer by participating in the regulation of JAK/ STAT pathway. [41][42][43][44] MAPKKK cascade is the key molecule in the MAPK pathway, and MAPK pathway can be incorporated to control cell propagation, invasion, migration, apoptosis, tumorigenesis, and progression of pancreatic tumor, as well as chemotherapy response and clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Identify potential clinical significance of long noncoding RNA forkhead box P4 antisense RNA 1 in patients with early stage pancreatic ductal adenocarcinoma

Liu

Chen

et al. 2020

Cancer Medicine

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Previous studies have shown that forkhead box P4 antisense RNA 1 (FOXP4‐AS1) is dysregulated in tumor tissues and can serve as a prognostic indicator for multiple cancers. However, the clinical significance of FOXP4‐AS1 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The goal of this study is to recognize the possible clinical significance of long noncoding RNA FOXP4‐AS1 in patients with early stage PDAC. A total of 112 patients from The Cancer Genome Atlas (TCGA) PDAC cohort, receiving RNA sequencing, were involved in the study. Survival analysis, functional mechanism, and potential small molecule drugs of target therapy of FOXP4‐AS1 were performed in this study. Survival analysis in TCGA PDAC cohort suggested that patients with high FOXP4‐AS1 expression had significantly augmented possibility of death than in PDAC patients with lower FOXP4‐AS1 expression (adjusted P = .008; adjusted HR = 2.143, 95% CI = 1.221‐3.760). In this study, a genome‐wide RNA sequencing dataset was used to identify 927 genes co‐expressing with FOXP4‐AS1 in PDAC tumor tissues. A total of 676 differentially expressed genes were identified between different FOXP4‐AS1 expression groups. Functional enrichment analysis of these genes and gene set enrichment analysis for PDAC genome‐wide RNA sequencing dataset was done. We have found that FOXP4‐AS1 may function in PDAC by participating in biological processes and pathways including oxidative phosphorylation, tricarboxylic acid cycle, classical tumor‐related pathways such as NF‐kappaB as well as Janus kinase/signal transducers in addition to activators of transcription, cell proliferation, and adhesion. In addition, we also screened two potential targeted therapeutic small molecule drugs (dimenhydrinate and metanephrine) for FOXP4‐AS1 in PDAC. In conclusion, our present study demonstrated that higher expression of FOXP4‐AS1 in PDAC tumor tissues were related with an inferior medical outcome. Through multiple genome‐wide approaches, we identified the potential molecular mechanisms of FOXP4‐AS1 in PDAC and two targeted therapeutic drugs for it.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identify potential clinical significance of long noncoding RNA forkhead box P4 antisense RNA 1 in patients with early stage pancreatic ductal adenocarcinoma

Liu

Chen

et al. 2020

Cancer Medicine

View full text Add to dashboard Cite

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“…Despite recent therapeutic advances, cancer remains among one of the leading causes of death worldwide, and the development of novel anti-tumor therapies is still a key priority. Clinical and experimental studies have documented the critical importance of an adequate blood supply for local solid tumor growth and distant metastasis (1)(2)(3)(4). Furthermore, the ability of tumor cells to induce new blood vessel growth is a determining factor in both tumor size and spread.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Dimethylarginine Dimethylaminohydrolase (DDAH) Enzymes as an Emerging Therapeutic Strategy to Target Angiogenesis and Vasculogenic Mimicry in Cancer

et al. 2020

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The small free radical gas nitric oxide (NO) plays a key role in various physiological and pathological processes through enhancement of endothelial cell survival and proliferation. In particular, NO has emerged as a molecule of interest in carcinogenesis and tumor progression due to its crucial role in various cancer-related events including cell invasion, metastasis, and angiogenesis. The dimethylarginine dimethylaminohydrolase (DDAH) family of enzymes metabolize the endogenous nitric oxide synthase (NOS) inhibitors, asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA), and are thus key for maintaining homeostatic control of NO. Dysregulation of the DDAH/ADMA/NO pathway resulting in increased local NO availability often promotes tumor growth, angiogenesis, and vasculogenic mimicry. Recent literature has demonstrated increased DDAH expression in tumors of different origins and has also suggested a potential ADMA-independent role for DDAH enzymes in addition to their well-studied ADMA-mediated influence on NO. Inhibition of DDAH expression and/or activity in cell culture models and in vivo studies has indicated the potential therapeutic benefit of this pathway through inhibition of both angiogenesis and vasculogenic mimicry, and strategies for manipulating DDAH function in cancer are currently being actively pursued by several research groups. This review will thus provide a timely discussion on the expression, regulation, and function of DDAH enzymes in regard to angiogenesis and vasculogenic mimicry, and will offer insight into the therapeutic potential of DDAH inhibition in cancer based on preclinical studies.

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“…For pancreatic cancer patients, the degree of in ammatory response can be measured by serum lactate dehydrogenase level and it is associated with outcome of the patients (53). Angiogenesis is out of control in PDAC, it also contributes to proliferation and deterioration of the tumor, making survival of patients worse (54,55).…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms

Liu

Liao

Wang

et al. 2020

Preprint

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Background: This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA).Methods: A total of 112 PDAC patients from TCGA were included in the analysis.The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) to identify potential underlying mechanisms.Results: High expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total score calculated. Genome-wide co-expression and GSEA analyses suggested that the GPC2 mechanisms affecting prognosis involved sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway.Conclusion: GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and the combination of these genes showed a higher efficiency for prognosis prediction.

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Angiogenesis in pancreatic cancer: current research status and clinical implications

Cited by 195 publications

References 204 publications

Identify potential clinical significance of long noncoding RNA forkhead box P4 antisense RNA 1 in patients with early stage pancreatic ductal adenocarcinoma

Identify potential clinical significance of long noncoding RNA forkhead box P4 antisense RNA 1 in patients with early stage pancreatic ductal adenocarcinoma

Inhibition of Dimethylarginine Dimethylaminohydrolase (DDAH) Enzymes as an Emerging Therapeutic Strategy to Target Angiogenesis and Vasculogenic Mimicry in Cancer

Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms

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