Plasma circulating tumor DNA in pancreatic adenocarcinoma for screening, diagnosis, prognosis, treatment and follow-up: A systematic review

Abdallah, Raëf; Taly, Valérie; Zhao, Shulin; Pietrasz, Daniel; Bachet, Jean‐Baptiste; Basile, Debora; Mas, Léo; Zaanan, Aziz; Laurent‐Puig, Pierre; Taı̈eb, Julien

doi:10.1016/j.ctrv.2020.102028

Cited by 8 publications

(4 citation statements)

References 87 publications

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“…Moreover, it is difficult to detect ctDNA due to the low concentration of ctDNA in the blood of patients in early staged of PC. Therefore, the quantification of ctDNA for the early diagnosis of PC is still challenging [ 23 ]. In recent years, the early diagnostic value of exosomal miRNA has also received attention, but the difficulty of exosome isolation and purification hinders its further promotion at this point.…”

Section: Discussionmentioning

confidence: 99%

Integrating a microRNA signature as a liquid biopsy-based tool for the early diagnosis and prediction of potential therapeutic targets in pancreatic cancer

Shi,

Wartmann,

Accuffi

et al. 2023

Br J Cancer

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Introduction Pancreatic cancer is a highly aggressive cancer, and early diagnosis significantly improves patient prognosis due to the early implementation of curative-intent surgery. Our study aimed to implement machine-learning algorithms to aid in early pancreatic cancer diagnosis based on minimally invasive liquid biopsies. Materials and methods The analysis data were derived from nine public pancreatic cancer miRNA datasets and two sequencing datasets from 26 pancreatic cancer patients treated in our medical center, featuring small RNAseq data for patient-matched tumor and non-tumor samples and serum. Upon batch-effect removal, systematic analyses for differences between paired tissue and serum samples were performed. The robust rank aggregation (RRA) algorithm was used to reveal feature markers that were co-expressed by both sample types. The repeatability and real-world significance of the enriched markers were then determined by validating their expression in our patients’ serum. The top candidate markers were used to assess the accuracy of predicting pancreatic cancer through four machine learning methods. Notably, these markers were also applied for the identification of pancreatic cancer and pancreatitis. Finally, we explored the clinical prognostic value, candidate targets and predict possible regulatory cell biology mechanisms involved. Results Our multicenter analysis identified hsa-miR-1246, hsa-miR-205-5p, and hsa-miR-191-5p as promising candidate serum biomarkers to identify pancreatic cancer. In the test dataset, the accuracy values of the prediction model applied via four methods were 94.4%, 84.9%, 82.3%, and 83.3%, respectively. In the real-world study, the accuracy values of this miRNA signatures were 82.3%, 83.5%, 79.0%, and 82.2. Moreover, elevated levels of these miRNAs were significant indicators of advanced disease stage and allowed the discrimination of pancreatitis from pancreatic cancer with an accuracy rate of 91.5%. Elevated expression of hsa-miR-205-5p, a previously undescribed blood marker for pancreatic cancer, is associated with negative clinical outcomes in patients. Conclusion A panel of three miRNAs was developed with satisfactory statistical and computational performance in real-world data. Circulating hsa-miRNA 205-5p serum levels serve as a minimally invasive, early detection tool for pancreatic cancer diagnosis and disease staging and might help monitor therapy success.

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Section: Discussionmentioning

confidence: 99%

Integrating a microRNA signature as a liquid biopsy-based tool for the early diagnosis and prediction of potential therapeutic targets in pancreatic cancer

Shi,

Wartmann,

Accuffi

et al. 2023

Br J Cancer

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“…In early stage PDAC, ctDNA was only detected in 30-65% of patients [41][42][43][44][45], while detectability improved to 70-80% in cases of more advanced disease [45,46]. However, it should also be noted that when using KRAS mutation, ctDNA has also been detected in up to 20% of cases with chronic pancreatitis and 17% of non-malignant pancreatic masses [47]. Therefore, this marker cannot reliably be used for early diagnosis, although detection of ctDNA does appear to be associated with worse prognosis.…”

Section: Diagnostic Biomarkersmentioning

confidence: 99%

Neoadjuvant Treatment for Pancreatic Adenocarcinoma: A False Promise or an Opportunity to Improve Outcome?

Khakoo

Petrillo

Salati

et al. 2021

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) has an aggressive tumor biology and is associated with poor survival outcomes. Most patients present with metastatic or locally advanced disease. In the 10–20% of patients with upfront resectable disease, surgery offers the only chance of cure, with the addition of adjuvant chemotherapy representing an established standard of care for improving outcomes. Despite resection followed by adjuvant chemotherapy, at best, 3-year survival reaches 63.4%. Post-operative complications and poor performance mean that around 50% of the patients do not commence adjuvant chemotherapy, and a significant proportion do not complete the intended treatment course. These factors, along with the advantages of early treatment of micrometastatic disease, the ability to downstage tumors, and the increase in R0 resection rates, have increased interest in neo-adjuvant treatment strategies. Here we review biomarkers for early diagnosis of PDAC and patient selection for a neo-adjuvant approach. We also review the current evidence for different chemotherapy regimens in this setting, as well as the role of chemoradiotherapy and immunotherapy, and we discuss ongoing trials.

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“…Among liquid biopsies, circulating tumor DNA (ctDNA) has a strong prognostic value, and its dynamic evolution under chemotherapy is correlated with treatment efficacy (13)(14)(15). There is no consensual methodology [digital polymerase chain reaction (PCR), next generation sequencing (NGS)], defined target (KRAS mutation, FGFR fusion, gene promoter methylation), or cut-off of mutant allelic frequency to detect it.…”

Section: Introductionmentioning

confidence: 99%

Performance of a blood-based RNA signature for gemcitabine-based treatment in metastatic pancreatic adenocarcinoma

Piquemal¹,

Bruno²,

Bournet³

et al. 2023

J Gastrointest Oncol

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Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, and chemotherapy is a key treatment for advanced PDAC. Gemcitabine chemotherapy is still an important component of treatment; however, there is no routine biomarker to predict its efficacy. Predictive tests may help clinicians to decide on the best first-line chemotherapy.Methods: This study is a confirmatory study of a blood-based RNA signature, called the GemciTest. This test measures the expression levels of nine genes using real-time polymerase chain reaction (PCR) processes.Clinical validation was carried out, through a discovery and a validation phases, on 336 patients (mean 68.7 years; range, 37-88 years) for whom blood was collected from two prospective cohorts and two tumor biobanks. These cohorts included previously untreated advanced PDAC patients who received either a gemcitabine-or fluoropyrimidine-based regimen.Results: Gemcitabine-based treated patients with a positive GemciTest (22.9%) had a significantly longer progression-free survival (PFS) [5.3 vs. 2.8 months; HR =0.53 (95% CI: 0.31-0.92); P=0.023] and OS [10.4 vs. 4.8 months; HR =0.49 (95% CI: 0.29-0.85); P=0.0091]. On the contrary, fluoropyrimidine-based treated patients showed no significant difference in PFS and OS using this blood signature. Conclusions:The GemciTest demonstrated that a blood-based RNA signature has the potential to aid in personalized therapy for PDAC, leading to better survival rates for patients receiving a gemcitabine-based first-line treatment.

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Plasma circulating tumor DNA in pancreatic adenocarcinoma for screening, diagnosis, prognosis, treatment and follow-up: A systematic review

Cited by 8 publications

References 87 publications

Integrating a microRNA signature as a liquid biopsy-based tool for the early diagnosis and prediction of potential therapeutic targets in pancreatic cancer

Integrating a microRNA signature as a liquid biopsy-based tool for the early diagnosis and prediction of potential therapeutic targets in pancreatic cancer

Neoadjuvant Treatment for Pancreatic Adenocarcinoma: A False Promise or an Opportunity to Improve Outcome?

Performance of a blood-based RNA signature for gemcitabine-based treatment in metastatic pancreatic adenocarcinoma

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