Dataset Information

Contributions of the Microbiome-Derived Metabolome for Risk Assessment and Prognostication of Pancreatic Cancer

ABSTRACT:

BACKGROUND Increasing evidence implicates microbiome involvement in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Studies suggest that reflux of gut or oral microbiota can lead to colonization in the pancreas, resulting in dysbiosis that culminates in release of microbial toxins and metabolites that potentiate an inflammatory response and increase susceptibility to PDAC. Moreover, microbe-derived metabolites can exert direct effector functions on precursors and cancer cells, as well as other cell types, to either promote or attenuate tumor development and modulate treatment response.

CONTENT The occurrence of microbial metabolites in biofluids thereby enables risk assessment and prognostication of PDAC, as well as having potential for design of interception strategies. In this review, we first highlight the relevance of the microbiome for progression of precancerous lesions in the pancreas and, using liquid chromatography-mass spectrometry, provide supporting evidence that microbe-derived metabolites manifest in pancreatic cystic fluid and are associated with malignant progression of intraductal papillary mucinous neoplasm(s). We secondly summarize the biomarker potential of microbe-derived metabolite signatures for (a) identifying individuals at high risk of developing or harboring PDAC and (b) predicting response to treatment and disease outcomes.

SUMMARY The microbiome-derived metabolome holds considerable promise for risk assessment and prognostication of PDAC.

INSTRUMENT(S): Liquid Chromatography MS - positive - hilic, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS7260 | MetaboLights | 2023-08-09

REPOSITORIES: MetaboLights

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	AllMetabolites_readouts.xlsx	Xlsx
	MTBLS7260.xlsx	Xlsx
	P_CA_PL079_B1_002_PQC1.d.zip	Other
	P_CA_PL079_B1_004_HQC.d.zip	Other
	P_CA_PL079_B1_006_PPIC4826_1101.d.zip	Other

Items per page:

1 - 5 of 4150

Publications

Contributions of the Microbiome-Derived Metabolome for Risk Assessment and Prognostication of Pancreatic Cancer.

León-Letelier Ricardo A RA Dou Rongzhang R Vykoukal Jody J Yip-Schneider Michele T MT Maitra Anirban A Irajizad Ehsan E Wu Ranran R Dennison Jennifer B JB Do Kim-An KA Zhang Jianjun J Schmidt C Max CM Hanash Samir S Fahrmann Johannes F JF

Clinical chemistry 20240101 1

<h4>Background</h4>Increasing evidence implicates microbiome involvement in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Studies suggest that reflux of gut or oral microbiota can lead to colonization in the pancreas, resulting in dysbiosis that culminates in release of microbial toxins and metabolites that potentiate an inflammatory response and increase susceptibility to PDAC. Moreover, microbe-derived metabolites can exert direct effector functions on precursors ...[more]

PMID: 38175578

Similar Datasets

Project description:Background: With less than a 5% survival rate pancreatic adenocarcinoma (PDAC) is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical. Methods and Findings: We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses. Conclusions: Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive/therapeutic targets for both familial and sporadic pancreatic adenocarcinoma. Gene expression of 13 PanIN samples was compared to profiling data of whole biopsies from normal donor pancreas (N1 to 4, two replicated samples) and sporadic PDAC (PDAC1 to 6).Ttwo PDAC samples (PDAC 3 and 4) and a replicate of one normal specimen (N4) were removed during the hybridisation quality assessment.