Oncogenomic Changes in Pancreatic Cancer and Their Detection in Stool

Abstract

Pancreatic cancer (PC) is an aggressive malignancy with a dismal prognosis. To improve patient survival, the development of screening methods for early diagnosis is pivotal. Oncogenomic alterations present in tumor tissue are a suitable target for non-invasive screening efforts, as they can be detected in tumor-derived cells, cell-free nucleic acids, and extracellular vesicles, which are present in several body fluids. Since stool is an easily accessible source, which enables convenient and cost-effective sampling, it could be utilized for the screening of these traces. Herein, we explore the various oncogenomic changes that have been detected in PC tissue, such as chromosomal aberrations, mutations in driver genes, epigenetic alterations, and differentially expressed non-coding RNA. In addition, we briefly look into the role of altered gut microbiota in PC and their possible associations with oncogenomic changes. We also review the findings of genomic alterations in stool of PC patients, and the potentials and challenges of their future use for the development of stool screening tools, including the possible combination of genomic and microbiota markers.

The connection between epigenetics and gut microbiota‐current perspective

“…Through the modulation of microRNAs (miRNAs), GM and their metabolites significantly influence our epigenome. For instance, the diet–microbiota–miRNAs axis is studied to be associated with the development of colorectal cancer (CRC) 30 . Moreover, it is also correlated with the epigenetic changes for pancreatic cancer, 31 cholangiocarcinoma 32 and biliary tract cancers 33 .…”

“…For instance, the diet-microbiota-miRNAs axis is studied to be associated with the development of colorectal cancer (CRC). 30 Moreover, it is also correlated with the epigenetic changes for pancreatic cancer, 31 cholangiocarcinoma 32 and biliary tract cancers. 33 Although the GM in carcinogenesis such as hepatocellular cancer (HCC) is associated with the immune dysregulation and instability of the host genome, epigenetic changes is a key factor in the progression from inflammation to cancer.…”

Pancreatic Cancer Research beyond DNA Mutations

“…Oncogenic mutations in tumor tissues are suitable targets for the noninvasive screening. Numerous efforts have been made to detect tumor-derived cells, cell-free nucleic acids, and extracellular vesicles present in several body fluids, including urine and feces [ 15 ]. Several efforts have been made to develop efficient technology to detect PDAC [ 15 , 16 , 17 ].…”

“…Numerous efforts have been made to detect tumor-derived cells, cell-free nucleic acids, and extracellular vesicles present in several body fluids, including urine and feces [ 15 ]. Several efforts have been made to develop efficient technology to detect PDAC [ 15 , 16 , 17 ]. A recent metagenomics study targeting the gut and oral microbiomes showed that it could provide a powerful source of biomarkers for identifying individuals with PDAC and their prognosis [ 16 ].…”

Early Diagnosis of Pancreatic Cancer: Clinical Premonitions, Timely Precursor Detection and Increased Curative-Intent Surgery

“…In theory, pancreatic juice with exfoliated cancer or pre-cancerous cells harbouring tumour-specific mutations may be secreted into the intestines and hence be discovered as mutations in the stool. This has indeed been investigated in a few studies, as reviewed by Sammallathi et al, 120 but has yet to make it into clinical practice. Related to this, is the specific microbiome and patterns related to alteration sin healthy compared to patients with cancer.…”