Clinical significance of promoter methylation status of tumor suppressor genes in circulating DNA of pancreatic cancer patients

Singh, Nidhi; Rashid, Safoora; Dash, Nihar Ranjan; Gupta, Surabhi; Saraya, Anoop

doi:10.1007/s00432-020-03169-y

Cited by 45 publications

(44 citation statements)

References 41 publications

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“…It was also found that in precancerous lesions of pancreatic cancer, the methylation of the NPTX2 promoter increases with the degree of abnormal proliferation, suggesting that NPTX2 promoter regional hypermethylation is associated with early tumorigenesis in pancreatic cancer (32,33). One study also found that pENK is highly methylated in pancreatic cancer tissue samples and pancreatic juice in pancreatic cancer patients, and its methylation to some extent promotes the formation of pancreatic cancer (34). In the present study, we found that the methylation of the miR-29 promoter was involved with malignant activities of pancreatic cancer cell lines.…”

Section: Discussionsupporting

confidence: 67%

Methylation of the miR‑29b‑3p promoter contributes to angiogenesis, invasion, and migration in pancreatic cancer

Wang

2020

Oncol Rep

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The aim of the present study was to investigate the effects of microRNA (miR)-29b-3p gene promoter methylation on angiogenesis, invasion, and migration in human pancreatic cancer. Prediction of promoter methylation of miR-29b-3p was performed through the MethPrimer tool. Then the methylation levels of miR-29b-3p in human pancreatic cancer tissues and cell lines were detected by pyrosequencing, and the relative expression of miR-29b-3p was assessed in pancreatic cancer tissues by qPCR. The results were analyzed by linear regression. Western blot analysis was used to detect expression of DNA methyltransferases (DNMTs) in pancreatic cancer tissues and adjacent tissues. The Transwell assay was used to detect the ability of cell migration and invasion. Cells were co-cultured with human umbilical vein endothelial cells (HUVECs) to detect the ability of angiogenesis. The results revealed that DNMT1 expression in pancreatic cancer tissues was higher than that in adjacent tissues. Further results showed that expression of miR-29b was negatively correlated with the methylation level of the miR-29b promoter. Bxpc3 and Capan-2 cells had higher methylation levels, and the expression level of miR-29b-3p in Bxpc3 and Capan-2 cells was found to be lower than that of other cell lines. Expression of zonula occludens-1 (ZO-1) and occludin was significantly increased, and the migration of cancer cells was decreased after cells were treated with siRNA DNMT1. Further results showed that miR-29b reversed the promotive effect of DNMT1 overexpression on tumor cell malignant properties. Methylation of the miR-29b-3p promoter contributes to angiogenesis, invasion, and migration in pancreatic cancer. This study indicated that the alteration of methylation of mR-19b may be a potential approach for inhibiting the progression of pancreatic cancer.

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Section: Discussionsupporting

confidence: 67%

Methylation of the miR‑29b‑3p promoter contributes to angiogenesis, invasion, and migration in pancreatic cancer

Wang

2020

Oncol Rep

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“…SPARC, which is also called osteonectin, is a component of the bone matrix that modulates cellular interactions with the extracellular matrix, exerting an adhesive, promigratory effect on cells. [72][73][74] Studies confirmed that high expression of SPARC in most of the tumors with a tendency for bone metastasis. 75,76 In PCa, Sarmishtha De et al treated tumor cells with different antagonists and conclude that tumor cells on the bone surface linked with SPARC exhibit αvβ3 expression.…”

Section: Vegf Promotes Pca Bone Metastasis By Controlling αVβ3 and Spmentioning

confidence: 71%

<p>Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target</p>

Tang¹,

Xu²,

Zhang³

et al. 2020

OTT

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In prostate cancer, distant organ metastasis is the leading cause of patient death. Although the mechanism of malignant tumor metastasis is unclear, studies have confirmed that integrin αVβ3 plays an important role in this process. In prostate cancer, αVβ3 mediates adhesion, invasion, immune escape and neovascularization through interactions with different ligands. Among these ligands and in addition to proteins that are directly related to tumor invasion, other proteins that contain the RGD structure could also bind to αVβ3 and cause a number of biological effects. In this article, we summarized the ligand and downstream proteins related to αVβ3-mediated prostate cancer metastasis as well as some diagnostic and therapeutic measures targeting αVβ3.

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“…If a person is suspected of having pancreatic cancer, his plasma sample may be collected and analyzed for his methylation status. Promoter methylation of other genes in blood can also be used as a potential indicator for early detection of PDAC, such as MUC2 and SPARC [20,22]. In addition, Curia et al [6] indicated that CpG methylation was observed in PDAC tissue, and hypermethylation level of PCDH10 was signi cantly associated with poor progression-free survival (PFS) rates.…”

Section: Discussionmentioning

confidence: 99%

A novel epigenetic signature for predicting the prognosis of pancreatic ductal adenocarcinoma

Zhao¹,

Li²,

Tan³

et al. 2020

Preprint

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Background Aberrant DNA methylation is often involved in carcinogenesis. This study is designed to establish an epigenetic signature to predict overall survival (OS) of pancreatic ductal adenocarcinoma (PDAC). Methods DNA methylation and RNA-seq data of PDAC patients were downloaded from the Cancer Genome Atlas database, Genotype-Tissue Expression (GTEx), and International Cancer Genome Consortium (ICGC) database. Methylation-related differentially expressed genes (DEGs) were identified using an R package MethylMix. Epigenetic signature and nomogram were established by the LASSO and multivariate Cox regression analysis, respectively. In addition, a joint survival analysis of the gene expression and methylation was performed to identify potential prognostic factors for patients with PDAC. Results There were a total of 56 methylation-related DEGs by MethylMix criteria. After LASSO Cox regression analysis, we developed an epigenetic signature composed of five genes according to their methylation level. The signature was able to divide patients into high-risk and low-risk groups, and the OS between the high-and low-risk groups was more significantly different in both training and validation cohort. The signature is independent of clinicopathological variables and indicated better predictive power. Moreover, we developed a novel prognostic nomogram that combines risk scores with three clinicopathological factors. The joint survival analysis of gene expression and methylation revealed that 24 genes could be independent prognostic factors for OS in PDAC. Conclusions The qualitative signature and nomogram that predict OS at the individualized level and guide therapy for patients with PDAC.

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Clinical significance of promoter methylation status of tumor suppressor genes in circulating DNA of pancreatic cancer patients

Cited by 45 publications

References 41 publications

Methylation of the miR‑29b‑3p promoter contributes to angiogenesis, invasion, and migration in pancreatic cancer

Methylation of the miR‑29b‑3p promoter contributes to angiogenesis, invasion, and migration in pancreatic cancer

<p>Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target</p>

A novel epigenetic signature for predicting the prognosis of pancreatic ductal adenocarcinoma

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