High Levels of Cell-Free Circulating Nucleic Acids in Pancreatic Cancer are Associated With Vascular Encasement, Metastasis and Poor Survival

Abstract

Pancreatic cancer is a highly aggressive disease with rapid invasion and early encasement of blood vessels. Hence, levels of circulating nucleic acids and tumor-associated mutations in them may have clinical importance. We analyzed the levels of circulating tumor DNA and oncogenic k-ras mutation in plasma of patients with pancreatic cancer and correlated their levels with survival and clinicopathological parameters. Higher levels of plasma DNA (>62 ng/mL) was found to associate significantly with lower overall survival time (p=.002), presence of vascular encasement (p=.030) and metastasis (p=.001). However, k-ras mutation status did not correlate with any of the clinicopathological parameters or survival. We conclude that circulating DNA in plasma can be an important predictor of prognosis in pancreatic cancer.

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

“…In a recent large meta-analysis, a high correlation between ccfDNA concentration and mCRC patient survival was observed, revealing that patients with relatively low levels of ccfDNA lived significantly longer than patients with higher levels (6). The relevance of ccfDNA levels for the prognosis of other cancer types has also been described, including advanced breast cancer (10), lung cancer (11,12), prostate cancer (13), pancreatic cancer (14), and other cancer types (15).…”

Extracellular DNA: A Bridge to Cancer

“…Based on the logical presumption that such "circulating DNA" in cancer patients is derived from dead tumor cells (2,43), interest in the potential for using the exDNA sequences as a "liquid biopsy" for diagnostic purposes has been high and the phenomenon has been documented in hundreds of papers (32,(48)(49)(50). A high degree of variability in the detection of tumor-specific markers in exDNA sequences, however, raises questions about the reliability of exDNA for diagnostic purposes based on the presumption that it is derived from dead tumor cells (32,33).…”

“…As Demers and Wagner (16) expressed it, the extracellular traps provide a "seeding soil" for cancer cells. This concept provides a new basis for interpreting long-standing observations that increased exDNA (also called circulating free DNA or cfDNA), and reduced DNase levels in human blood occur in correlation with cancer development and progression (25)(26)(27)(28)(29)(30)(31)(32)(33). Studies by independent laboratories around the world, moreover, repeatedly have documented that DNase 1 added to diverse cancer cells inhibits their metastatic potential (30,(34)(35)(36)(37)(38)(39)(40)(41).…”

“…Meanwhile, the values for exDNA in blood have been proposed to comprise important clinical information regardless of whether future studies reveal that the exDNA includes tumor sequences and/or is derived of extracellular trap DNA (33). Either model could account for observations that the exDNA of cancer patients can facilitate oncogenic transformation, and that DNase I treatment of cancer cells or the supernatants of cancer patients removes the capacity to metastasize (30,36,40,41).…”

Detection of K‑ras gene mutations in feces by magnetic nanoprobe in patients with pancreatic cancer: A preliminary study

“…K-ras is able to bind guanine nucleotides within a growth factor signal transduction pathway, while pathological mutations of K-ras lead to cell proliferation (9). The detection of K-ras mutations in biopsy specimens, pancreatic juice, bile and blood has been previously reported (10,11). Genetic mutations detected in biopsy specimens and pancreatic juice may be a reliable method for diagnosing pancreatic cancer; however, it is challenging to obtain adequate samples (12).…”