Analysis of circulating cell-free DNA identifies KRAS copy number gain and mutation as a novel prognostic marker in Pancreatic cancer

Mohan, Sumitra; Ayub, Mahmood; Rothwell, Dominic G.; Gulati, Sakshi; Kilerci, Bedirhan; Hollebecque, Antoine; Leong, Hui Sun; Smith, Nigel; Sahoo, Sudhakar; Descamps, Tine; Zhou, Cong; Hubner, Richard A; McNamara, Mairéad G.; Lamarca, Ángela; Valle, Juan W.; Dive, Caroline; Brady, Ged

doi:10.1038/s41598-019-47489-7

Cited by 41 publications

(49 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 85% of all pancreatic tumors, and the overall 5-year survival rate of patients with PDAC less than 7%. 2,3 Clinically, surgery, chemotherapy, radiation therapy and immunotherapy are the main treatment methods for pancreatic cancer. 4 However, the survival rate and prognosis of patients with pancreatic cancer remain worse.…”

Section: Introductionmentioning

confidence: 99%

<p>Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells</p>

Wang

Liu

Sun

et al. 2020

OTT

View full text Add to dashboard Cite

These authors contributed equally to this work Background: 5-Fluorouracil (5-Fu) has been applied to treat pancreatic cancer, which is one of the most common types of digestive system tumors. Evidence has shown that miR-486-5p could promote the proliferation of pancreatic cancer cells. Therefore, this study aimed to investigate whether downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells. Methods: Cell Counting Kit 8 assay, flow cytometry and wound healing assays were used to detect proliferation, apoptosis and migration in PANC-1 cells. The expressions of Bcl-2, Bax, cleaved caspase 3, PTEN, p-Akt and p-ERK in PANC-1 cells were detected with Western blot assay. Results: In this study, the inhibitory effects of 5-Fu on the proliferation, migration and invasion of PANC-1 cells were significantly enhanced following transfection with miR-486-5p antagonist. In addition, downregulation of miR-486-5p markedly enhanced the proapoptosis effect of 5-Fu on PANC-1 cells. Moreover, bioinformatics analysis and luciferase reporter assay identified that PTEN was the directly binding target of miR-486-5p. Meanwhile, downregulation of miR-486-5p markedly enhanced the anti-tumor effect of 5-Fu in PANC-1 cells via upregulation of the level of PTEN, and downregulation of the expressions of p-ERK and p-Akt. In vivo experiments confirmed that knockdown of miR-486-5p could enhance the anti-tumor effect of 5-Fu in PANC-1 xenograft model. Conclusion: We found that the downregulation of miR-486-5p could enhance the antitumor effect of 5-Fu on pancreatic cancer cells. Therefore, miR-486-5p antagonist plus 5-Fu might be considered as a potential therapeutic strategy for the treatment of pancreatic cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

<p>Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells</p>

Wang

Liu

Sun

et al. 2020

OTT

View full text Add to dashboard Cite

show abstract

“…All of the included studies had OS outcomes, while 5 of them had PFS prognostic data [ 21 , 28 , 32 , 35 , 36 ]. Seven studies included patients with PC of all stages (stage: I - IV) [ 23 – 26 , 29 , 32 , 33 ], 8 studies included patients with resectable PC (stage: I - II) [ 21 , 22 , 27 , 31 , 35 , 37 , 38 , 42 ], and 12 studies included patients with advanced PC (stage: III - IV) [ 18 – 20 , 22 , 28 , 30 , 31 , 34 , 36 , 39 – 41 ]. All of the included studies sampled at baseline, and 4 of them had postoperative data [ 21 , 31 , 35 , 38 ].…”

Section: Resultsmentioning

confidence: 99%

Prognostic value of circulating tumor DNA in pancreatic cancer: a systematic review and meta-analysis

Fang

Meng

Zhang

et al. 2020

Aging

View full text Add to dashboard Cite

Increasing evidence has revealed the potential correlation between circulating tumor DNA (ctDNA) and the prognosis of pancreatic cancer, but inconsistent findings have been reported. Therefore, a meta-analysis was performed to evaluate the prognostic value of ctDNA in pancreatic cancer. The Embase, MEDLINE, and Web of Science databases were searched for relevant articles published until April 2020. Articles reporting the correlation between ctDNA and the prognosis of pancreatic cancer were identified through database searches. The pooled hazard ratios (HRs) for prognostic data were calculated and analyzed using Stata software. A total of 2326 patients pooled from 25 eligible studies were included in the meta-analysis to evaluate the prognostic value of ctDNA in pancreatic cancer. Patients with mutations detected or high concentrations of ctDNA had a significantly poorer overall survival (OS) (univariate: HR = 2.54; 95% CI, 2.05-3.14; multivariate: HR = 2.07; 95% CI, 1.69-2.54) and progression-free survival (PFS) (univariate: HR = 2.18; 95% CI, 1.41-3.37; multivariate: HR = 2.20; 95% CI, 1.38-3.52). In conclusion, the present meta-analysis indicates that mutations detected or high concentrations of ctDNA are significant predictors of OS and PFS in patients with pancreatic cancer.

show abstract

“…Despite the potential of ddPCR to identify ctDNA KRAS mutations, most studies have analyzed KRAS mutations in ctDNA in order to verify the corresponding mutation in matched tumor tissues [ 57 , 69 ]. Finally, KRAS alleles have been assessed by quantitative ddPCR in a large series of patients with PDAC, pre-neoplastic pancreatic cyst and non-neoplastic pancreatic diseases [ 48 , 49 ].…”

Section: Increasing Genetic Knowledge To Improve Clinical Practicementioning

confidence: 99%

Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review

Huerta

Roselló

Sabater

et al. 2021

Cancers

View full text Add to dashboard Cite

Pancreatic cancer (PC) is one of the most devastating malignant tumors, being the seventh leading cause of cancer-related death worldwide. Researchers and clinicians are endeavoring to develop strategies for the early detection of the disease and the improvement of treatment results. Adequate biopsy is still challenging because of the pancreas’s poor anatomic location. Recently, circulating tumor DNA (ctDNA) could be identified as a liquid biopsy tool with huge potential as a non-invasive biomarker in early diagnosis, prognosis and management of PC. ctDNA is released from apoptotic and necrotic cancer cells, as well as from living tumor cells and even circulating tumor cells, and it can reveal genetic and epigenetic alterations with tumor-specific and individual mutation and methylation profiles. However, ctDNA sensibility remains a limitation and the accuracy of ctDNA as a biomarker for PC is relatively low and cannot be currently used as a screening or diagnostic tool. Increasing evidence suggests that ctDNA is an interesting biomarker for predictive or prognosis studies, evaluating minimal residual disease, longitudinal follow-up and treatment management. Promising results have been published and therefore the objective of our review is to understand the current role and the future perspectives of ctDNA in PC.

show abstract

Analysis of circulating cell-free DNA identifies KRAS copy number gain and mutation as a novel prognostic marker in Pancreatic cancer

Cited by 41 publications

References 17 publications

<p>Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells</p>

<p>Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells</p>

Prognostic value of circulating tumor DNA in pancreatic cancer: a systematic review and meta-analysis

Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review

Contact Info

Product

Resources

About