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Circulating DNA and Micro-RNA in Patients with Pancreatic Cancer.

Vietsch EE, van Eijck CH, Wellstein A - Pancreat Disord Ther (2015)

Bottom Line: Circulating miR expression patterns can be established from serial serum samples and monitored for alterations over time.Furthermore, changes in circulating miR patterns can indicate treatment efficacy or resistance as well as adverse effects associated with the respective intervention.Thus, the combined serial analysis of mutant DNA and miR in the circulation has the potential to provide a molecular footprint of pancreatic cancer and can be used to monitor treatment responses or resistance to treatment in real time with a minimally invasive procedure.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.

ABSTRACT

Collecting repeat samples of blood ("liquid biopsies") is a broadly used clinical approach for serial monitoring of disease or response to treatments. In patients with cancer the most distinct molecular feature are somatic mutations acquired by cancer cells present in the diseased tissue. Indeed, mutant DNA derived from dying or lysed cancer cells can be isolated from patient serum samples, subjected to DNA sequencing and to analysis of abundance as a measure of tumor burden. Also, changes in the DNA mutation patterns in serum samples collected over time can indicate altered pathways or clonal evolution of the disease and altered abundance of mutant DNA suggests an altered disease burden. In addition, during the course of treatment, changes in circulating DNA mutation patterns can indicate the emergence of resistant clones and prompt changes in treatment. In contrast to mutant DNA, microRNAs (miR) are transcribed, processed, packaged and released from cells in normal and in diseased tissues as part of the extracellular crosstalk between cells. Interestingly, released miR can function in cell-to-cell communication and as hormone-like signals that operate at a distance through their release into the circulation and subsequent uptake into cells in distant tissues. Circulating miR expression patterns can be established from serial serum samples and monitored for alterations over time. Circulating miR provide a readout of the organism's steady state and serial analyses will indicate changes in the response to therapy or an altered physiologic or disease state. Furthermore, changes in circulating miR patterns can indicate treatment efficacy or resistance as well as adverse effects associated with the respective intervention. Thus, the combined serial analysis of mutant DNA and miR in the circulation has the potential to provide a molecular footprint of pancreatic cancer and can be used to monitor treatment responses or resistance to treatment in real time with a minimally invasive procedure.

No MeSH data available.


Related in: MedlinePlus

Release of cell free DNA and miR into the circulation. Healthy organs e.g. brain, lung, heart, kidney, liver, bone marrow shed miR and wild type DNA into the bloodstream as indicated by the dotted arrows. The pancreatic cancer (enlarged area) is depicted as cancer cells (colored) and stromal cells (grey). Tumor-derived mutated DNA originates from the heterogeneous cancer cell population and is shed into the circulation as cell-free (cf) DNA or from apoptotic cancer cells that entered the circulation. MicroRNAs derived from normal and from tumor tissues reflect the composite of signaling in cancer cells, stroma and normal tissues. Double helices indicate cfDNA, short, single-stranded nucleic acids in different colors indicate miR.
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Figure 1: Release of cell free DNA and miR into the circulation. Healthy organs e.g. brain, lung, heart, kidney, liver, bone marrow shed miR and wild type DNA into the bloodstream as indicated by the dotted arrows. The pancreatic cancer (enlarged area) is depicted as cancer cells (colored) and stromal cells (grey). Tumor-derived mutated DNA originates from the heterogeneous cancer cell population and is shed into the circulation as cell-free (cf) DNA or from apoptotic cancer cells that entered the circulation. MicroRNAs derived from normal and from tumor tissues reflect the composite of signaling in cancer cells, stroma and normal tissues. Double helices indicate cfDNA, short, single-stranded nucleic acids in different colors indicate miR.

Mentions: Pancreatic cancer is a deadly malignant disease with surgical resection currently the only potentially curative modality although only 10–20% of patients are diagnosed with a resectable tumor [1,2]. Patients with advanced or metastatic disease receive chemotherapy with either gemcitabine or S-1, an oral fluoropyrimidine, or with the combination treatment FOLFIRINOX [3–5]. The prognosis of patients receiving surgery and chemotherapy is dependent on a number of characteristics including radiographical staging, histological grading, ECOG scores and CA19-9 levels [6–8]. However, very little improvement in the outcomes of patients with pancreatic cancer has been seen in the past 30 years [1]. Here we will review the potential to use blood samples or “liquid biopsies”, a recent term coined to indicate the relation to cancer tissue analysis, as markers of genetic characterization of a cancerous lesion. It is conceivable that blood samples can reflect the mutation profile of a primary cancer as well as residual cancer cells that are not accessible physically or below detection. Additionally, liquid biopsies can be taking repeatedly to follow evolution of the disease. Identification of specific pancreatic cancer markers is crucial for the improvement of controlling this disease and recent studies have shown that circulating mutant DNA can be found in the majority of cancer patients and can provide a measurement of tumor burden. Moreover, it could be used to identify specific mutant genotypes emerging from a heterogeneous tumor population. In contrast to the unique source of mutant DNA, i.e. cancer cells, miR isolated from the circulation is derived from virtually all tissues in the organism (Figure 1.) The analysis of expression patterns of circulating miR will thus provide a footprint of the steady state of the organism that encompasses normal as well as pathologic processes. Also, it will reflect the impact of therapeutic interventions on the diseased as well as healthy tissues. Here we review the published data on circulating nucleic acids, i.e. DNA and miR that reflect the disease state and treatment responses of patients with pancreatic cancer.


Circulating DNA and Micro-RNA in Patients with Pancreatic Cancer.

Vietsch EE, van Eijck CH, Wellstein A - Pancreat Disord Ther (2015)

Release of cell free DNA and miR into the circulation. Healthy organs e.g. brain, lung, heart, kidney, liver, bone marrow shed miR and wild type DNA into the bloodstream as indicated by the dotted arrows. The pancreatic cancer (enlarged area) is depicted as cancer cells (colored) and stromal cells (grey). Tumor-derived mutated DNA originates from the heterogeneous cancer cell population and is shed into the circulation as cell-free (cf) DNA or from apoptotic cancer cells that entered the circulation. MicroRNAs derived from normal and from tumor tissues reflect the composite of signaling in cancer cells, stroma and normal tissues. Double helices indicate cfDNA, short, single-stranded nucleic acids in different colors indicate miR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494744&req=5

Figure 1: Release of cell free DNA and miR into the circulation. Healthy organs e.g. brain, lung, heart, kidney, liver, bone marrow shed miR and wild type DNA into the bloodstream as indicated by the dotted arrows. The pancreatic cancer (enlarged area) is depicted as cancer cells (colored) and stromal cells (grey). Tumor-derived mutated DNA originates from the heterogeneous cancer cell population and is shed into the circulation as cell-free (cf) DNA or from apoptotic cancer cells that entered the circulation. MicroRNAs derived from normal and from tumor tissues reflect the composite of signaling in cancer cells, stroma and normal tissues. Double helices indicate cfDNA, short, single-stranded nucleic acids in different colors indicate miR.
Mentions: Pancreatic cancer is a deadly malignant disease with surgical resection currently the only potentially curative modality although only 10–20% of patients are diagnosed with a resectable tumor [1,2]. Patients with advanced or metastatic disease receive chemotherapy with either gemcitabine or S-1, an oral fluoropyrimidine, or with the combination treatment FOLFIRINOX [3–5]. The prognosis of patients receiving surgery and chemotherapy is dependent on a number of characteristics including radiographical staging, histological grading, ECOG scores and CA19-9 levels [6–8]. However, very little improvement in the outcomes of patients with pancreatic cancer has been seen in the past 30 years [1]. Here we will review the potential to use blood samples or “liquid biopsies”, a recent term coined to indicate the relation to cancer tissue analysis, as markers of genetic characterization of a cancerous lesion. It is conceivable that blood samples can reflect the mutation profile of a primary cancer as well as residual cancer cells that are not accessible physically or below detection. Additionally, liquid biopsies can be taking repeatedly to follow evolution of the disease. Identification of specific pancreatic cancer markers is crucial for the improvement of controlling this disease and recent studies have shown that circulating mutant DNA can be found in the majority of cancer patients and can provide a measurement of tumor burden. Moreover, it could be used to identify specific mutant genotypes emerging from a heterogeneous tumor population. In contrast to the unique source of mutant DNA, i.e. cancer cells, miR isolated from the circulation is derived from virtually all tissues in the organism (Figure 1.) The analysis of expression patterns of circulating miR will thus provide a footprint of the steady state of the organism that encompasses normal as well as pathologic processes. Also, it will reflect the impact of therapeutic interventions on the diseased as well as healthy tissues. Here we review the published data on circulating nucleic acids, i.e. DNA and miR that reflect the disease state and treatment responses of patients with pancreatic cancer.

Bottom Line: Circulating miR expression patterns can be established from serial serum samples and monitored for alterations over time.Furthermore, changes in circulating miR patterns can indicate treatment efficacy or resistance as well as adverse effects associated with the respective intervention.Thus, the combined serial analysis of mutant DNA and miR in the circulation has the potential to provide a molecular footprint of pancreatic cancer and can be used to monitor treatment responses or resistance to treatment in real time with a minimally invasive procedure.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.

ABSTRACT

Collecting repeat samples of blood ("liquid biopsies") is a broadly used clinical approach for serial monitoring of disease or response to treatments. In patients with cancer the most distinct molecular feature are somatic mutations acquired by cancer cells present in the diseased tissue. Indeed, mutant DNA derived from dying or lysed cancer cells can be isolated from patient serum samples, subjected to DNA sequencing and to analysis of abundance as a measure of tumor burden. Also, changes in the DNA mutation patterns in serum samples collected over time can indicate altered pathways or clonal evolution of the disease and altered abundance of mutant DNA suggests an altered disease burden. In addition, during the course of treatment, changes in circulating DNA mutation patterns can indicate the emergence of resistant clones and prompt changes in treatment. In contrast to mutant DNA, microRNAs (miR) are transcribed, processed, packaged and released from cells in normal and in diseased tissues as part of the extracellular crosstalk between cells. Interestingly, released miR can function in cell-to-cell communication and as hormone-like signals that operate at a distance through their release into the circulation and subsequent uptake into cells in distant tissues. Circulating miR expression patterns can be established from serial serum samples and monitored for alterations over time. Circulating miR provide a readout of the organism's steady state and serial analyses will indicate changes in the response to therapy or an altered physiologic or disease state. Furthermore, changes in circulating miR patterns can indicate treatment efficacy or resistance as well as adverse effects associated with the respective intervention. Thus, the combined serial analysis of mutant DNA and miR in the circulation has the potential to provide a molecular footprint of pancreatic cancer and can be used to monitor treatment responses or resistance to treatment in real time with a minimally invasive procedure.

No MeSH data available.


Related in: MedlinePlus