Open AccessFragmentation of cell‐free DNA is induced by upper‐tract urothelial carcinoma–associated systemic inflammation
Author(s) -
Nakano Kosuke,
Yamamoto Yoshiyuki,
Yamamichi Gaku,
Yumiba Satoru,
Tomiyama Eisuke,
Matsushita Makoto,
Koh Yoko,
Hayashi Yujiro,
Wang Cong,
Ishizuya Yu,
Kato Taigo,
Hatano Koji,
Kawashima Atsunari,
Ujike Takeshi,
Fujita Kazutoshi,
omura Norio,
Uemura Motohide
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14679
Subject(s) - medicine , interleukin 1 receptor antagonist , biomarker , cell free fetal dna , systemic inflammation , odds ratio , gastroenterology , inflammation , confidence interval , peripheral blood mononuclear cell , fragmentation (computing) , oncology , urology , antagonist , receptor antagonist , receptor , biology , pregnancy , ecology , biochemistry , fetus , genetics , prenatal diagnosis , in vitro
Reliable biomarkers for upper‐tract urothelial carcinoma (UTUC) have yet to be found. Plasma cell‐free DNA (cfDNA) has been clinically applied as a minimally invasive blood biomarker for various types of cancer. We investigated the utility of plasma cfDNA as a blood biomarker in UTUC patients. The fragment size of plasma cfDNA was shorter and the concentration of plasma cfDNA was higher in UTUC patients than in healthy controls. The fragment size of plasma cfDNA had a moderate accuracy of diagnosing UTUC (area under the curve [AUC] = 0.72), and multivariate analysis indicated that the fragment size of plasma cfDNA was significantly associated with the presence of UTUC (odds ratio = 0.807, 95% confidence interval [CI] 0.653‐0.955, P = .024). Furthermore, we found that the size of plasma cfDNA shortens alongside disease progression ( P < .001). The fragment size of plasma cfDNA in UTUC patients may be an auxiliary tool for the diagnosis of UTUC patients. We also found a high correlation between the fragmentation of plasma cfDNA and serum levels of three inflammatory cytokines (TNFα [ r = −.837], interleukin‐6 [IL‐6] [ r = −.964], interleukin‐1 receptor antagonist [IL‐1ra] [ r = −.911]), which were reported to associate with poor prognosis. Also, we found that the proportion of short fragments of cfDNA was significantly increased in the supernatant of peripheral blood mononuclear cells (PBMCs) from healthy controls cultured in media containing TNFα. These results supposed that cancer‐associated systemic inflammation, especially tumor necrosis factor‐α (TNFα), may contribute to the fragmentation of plasma cfDNA in UTUC patients.