Fragment size and level of cell-free DNA provide prognostic information in patients with advanced pancreatic cancer - PubMed (original) (raw)

Fragment size and level of cell-free DNA provide prognostic information in patients with advanced pancreatic cancer

Morten Lapin et al. J Transl Med. 2018.

Abstract

Background: It was recently demonstrated that the size of cell-free DNA (cfDNA) fragments that originates from tumor cells are shorter than cfDNA fragments that originates from non-malignant cells. We investigated whether cfDNA fragment size and cfDNA levels might have prognostic value in patients with advanced pancreatic cancer.

Methods: Blood samples were obtained from patients with advanced pancreatic cancer, before (n = 61) initiation of chemotherapy and after the first cycle of chemotherapy (n = 39). Samples were separated with density centrifugation and plasma DNA was isolated. Mode cfDNA fragment size and cfDNA levels were then determined using a 2100 Bioanalyzer. A cohort of partially age-matched healthy volunteers (n = 28) constituted the control group.

Results: Both a pre-treatment cfDNA fragment size of ≤ 167 bp (mode) and high pre-treatment cfDNA levels were associated with shorter progression-free survival (PFS) (p = 0.002 and p < 0.001, respectively) and overall survival (OS) (p = 0.001 and p = 0.001, respectively). Furthermore, multivariable Cox regression analyses demonstrated that pre-treatment cfDNA levels could independently predict prognosis for both PFS (HR = 3.049, p = 0.005) and OS (HR = 2.236, p = 0.028).

Conclusion: This study demonstrates that cfDNA fragment size and cfDNA levels can be used to predict disease outcome in patients with advanced pancreatic cancer. The described approach, using a rapid, economic and simple test to reveal prognostic information, has potential for future treatment stratification and monitoring.

Keywords: Cell-free DNA; Pancreatic cancer; cfDNA; cfDNA fragment size.

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Figures

Fig. 1

Fig. 1

Distribution of cfDNA fragment size and cfDNA level in plasma. a cfDNA from healthy controls (n = 10) displayed larger fragment size (X-axis) and lower cfDNA level (Y-axis) compared to b cfDNA from patients with pancreatic cancer (n = 10). The dotted line placed at 150 bp indicates a shift towards shorter fragment size in patient samples

Fig. 2

Fig. 2

Distributions of cfDNA fragment size and cfDNA levels in patient and control samples. Boxplot shows differences in a cfDNA fragment size and b cfDNA levels between samples from healthy controls (n = 28), patients with localized disease (n = 6), and patients with metastatic disease (n = 55). Abbreviation: n.s, not significant

Fig. 3

Fig. 3

Kaplan-Meier analyses of pre-treatment samples. a, c, e Progression-free survival and b, d, f overall survival are shown for a, b patients with short (≤ 167 bp) vs those with long (> 167 bp) cfDNA fragment size; c, d patients with high vs those with low cfDNA levels, and e, f patients positive for two markers, vs those with one or no markers

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