Dataset Information

Omics Approaches in Pancreatic Adenocarcinoma.

ABSTRACT: Pancreatic ductal adenocarcinoma, which represents 80% of pancreatic cancers, is mainly diagnosed when treatment with curative intent is not possible. Consequently, the overall five-year survival rate is extremely dismal-around 5% to 7%. In addition, pancreatic cancer is expected to become the second leading cause of cancer-related death by 2030. Therefore, advances in screening, prevention and treatment are urgently needed. Fortunately, a wide range of approaches could help shed light in this area. Beyond the use of cytological or histological samples focusing in diagnosis, a plethora of new approaches are currently being used for a deeper characterization of pancreatic ductal adenocarcinoma, including genetic, epigenetic, and/or proteo-transcriptomic techniques. Accordingly, the development of new analytical technologies using body fluids (blood, bile, urine, etc.) to analyze tumor derived molecules has become a priority in pancreatic ductal adenocarcinoma due to the hard accessibility to tumor samples. These types of technologies will lead us to improve the outcome of pancreatic ductal adenocarcinoma patients.

SUBMITTER: Gonzalez-Borja I

PROVIDER: S-EPMC6721316 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Omics Approaches in Pancreatic Adenocarcinoma.

González-Borja Iranzu I Viúdez Antonio A Goñi Saioa S Santamaria Enrique E Carrasco-García Estefania E Pérez-Sanz Jairo J Hernández-García Irene I Sala-Elarre Pablo P Arrazubi Virginia V Oyaga-Iriarte Esther E Zárate Ruth R Arévalo Sara S Sayar Onintza O Vera Ruth R Fernández-Irigoyen Joaquin J

Cancers 20190725 8

Pancreatic ductal adenocarcinoma, which represents 80% of pancreatic cancers, is mainly diagnosed when treatment with curative intent is not possible. Consequently, the overall five-year survival rate is extremely dismal-around 5% to 7%. In addition, pancreatic cancer is expected to become the second leading cause of cancer-related death by 2030. Therefore, advances in screening, prevention and treatment are urgently needed. Fortunately, a wide range of approaches could help shed light in this a ...[more]

PMID: 31349663

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Project description:The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is associated with the tumour heterogeneity. To explore intra- and inter-tumoural heterogeneity in PDAC, we analysed the multi-omics profiles of 61 PDAC lesion samples, along with the matched pancreatic normal tissue samples, from 19 PDAC patients. Haematoxylin and Eosin (H&E) staining revealed that diversely differentiated lesions coexisted both within and across individual tumours. Whole exome sequencing (WES) of samples from multi-region revealed diverse types of mutations in diverse genes between cancer cells within a tumour and between tumours from different individuals. The copy number variation (CNV) analysis also showed that PDAC exhibited intra- and inter-tumoural heterogeneity in CNV and that high average CNV burden was associated poor prognosis of the patients. Phylogenetic tree analysis and clonality/timing analysis of mutations displayed diverse evolutionary pathways and spatiotemporal characteristics of genomic alterations between different lesions from the same or different tumours. Hierarchical clustering analysis illustrated higher inter-tumoural heterogeneity than intra-tumoural heterogeneity of PDAC at the transcriptional levels as lesions from the same patients are grouped into a single cluster. Immune marker genes are differentially expressed in different regions and tumour samples as shown by tumour microenvironment (TME) analysis. TME appeared to be more heterogeneous than tumour cells in the same patient. Lesion-specific differentially methylated regions (DMRs) were identified by methylated DNA immunoprecipitation sequencing (MeDIP-seq). Furthermore, the integration analysis of multi-omics data showed that the mRNA levels of some genes, such as PLCB4, were significantly correlated with the gene copy numbers. The mRNA expressions of potential PDAC biomarkers ZNF521 and KDM6A were correlated with copy number alteration and methylation, respectively. Taken together, our results provide a comprehensive view of molecular heterogeneity and evolutionary trajectories of PDAC and may guide personalised treatment strategies in PDAC therapy.

Project description:IntroductionPancreatic adenocarcinoma (PAC) has some of the worst treatment outcomes for any solid tumor. PAC creates substantial difficulty for effective treatment with traditional RT delivery strategies primarily secondary to its location and limited visualization using CT. Several of these challenges are uniquely addressed with MR-guided RT. We sought to summarize and place into context the currently available literature on MR-guided RT specifically for PAC.MethodsA literature search was conducted to identify manuscript publications since September 2014 that specifically used MR-guided RT for the treatment of PAC. Clinical outcomes of these series are summarized, discussed, and placed into the context of the existing pancreatic literature. Multiple international experts were involved to optimally contextualize these publications.ResultsOver 300 manuscripts were reviewed. A total of 6 clinical outcomes publications were identified that have treated patients with PAC using MR guidance. Successes, challenges, and future directions for this technology are evident in these publications. MR-guided RT holds theoretical promise for the treatment of patients with PAC. As with any new technology, immediate or dramatic clinical improvements associated with its use will take time and experience. There remain no prospective trials, currently publications are limited to small retrospective experiences. The current level of evidence for MR guidance in PAC is low and requires significant expansion. Future directions and ongoing studies that are currently open and accruing are identified and reviewed.ConclusionsThe potential promise of MR-guided RT for PAC is highlighted, the challenges associated with this novel therapeutic intervention are also reviewed. Outcomes are very early, and will require continued and long term follow up. MR-guided RT should not be viewed in the same fashion as a novel chemotherapeutic agent for which dosing, administration, and toxicity has been established in earlier phase studies. Instead, it should be viewed as a novel procedural intervention which must be robustly tested, refined and practiced before definitive conclusions on the potential benefits or detriments can be determined. The future of MR-guided RT for PAC is highly promising and the potential implications on PAC are substantial.

Dataset Information

Omics Approaches in Pancreatic Adenocarcinoma.

Publications

Omics Approaches in Pancreatic Adenocarcinoma.

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