Serum cell‐free DNA as a new biomarker in cutaneous T‐cell lymphoma

In recent years, circulating cell‐free DNA (cfDNA) has received a great attention as a biomarker for various cancers. Many reports have shown that serum cfDNA levels are elevated in cancer patients and their levels correlate with prognosis and disease activity. The aim of this study was to measure serum cfDNA levels in patients with cutaneous T‐cell lymphoma (CTCL) and to evaluate their correlations with hematological and clinical findings. Serum cfDNA levels in CTCL patients were significantly higher than those in healthy controls, and their levels gradually increased with the progression of the disease stage. Positive correlations were detected between serum cfDNA levels and those of lactate dehydrogenase, thymus and activation‐regulated chemokine and soluble IL‐2 receptor as well as neutrophil and eosinophil count in peripheral blood and neutrophil‐to‐lymphocyte ratio. Furthermore, CTCL patients with higher serum cfDNA levels exhibited a significantly worse prognosis. Taken together, these results suggest the potential of cfDNA as a new biomarker reflecting prognosis and disease activity in CTCL. CfDNA levels may serve as an indicator for considering the intensity and timing of subsequent therapeutic intervention.

[1]  L. Alekseeva,et al.  Role of Cell-Free DNA and Deoxyribonucleases in Tumor Progression , 2021, International Journal of Molecular Sciences.

[2]  D. Ward,et al.  Circulating tumour DNA (ctDNA) in metastatic melanoma, a systematic review and meta-analysis. , 2021, European journal of cancer.

[3]  J. Manzo-Merino,et al.  The role of extracellular DNA (exDNA) in cellular processes , 2021, Cancer biology & therapy.

[4]  R. Yamashita,et al.  Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies , 2020, Nature Medicine.

[5]  Sourav Bandyopadhyay,et al.  Cutaneous T cell lymphoma PDX drug screening platform identifies cooperation between inhibitions of PI3Kα/δ and HDAC. , 2020, The Journal of investigative dermatology.

[6]  M. Speicher,et al.  Cell-Free DNA and Apoptosis: How Dead Cells Inform About the Living. , 2020, Trends in molecular medicine.

[7]  F. Mouliere,et al.  Toward the Early Detection of Cancer by Decoding the Epigenetic and Environmental Fingerprints of Cell-Free DNA. , 2019, Cancer cell.

[8]  E. Jaffe,et al.  The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. , 2019, Blood.

[9]  T. Peretz,et al.  Life and death of circulating cell-free DNA , 2019, Cancer biology & therapy.

[10]  S. Holdenrieder,et al.  The emerging role of cell-free DNA as a molecular marker for cancer management , 2019, Biomolecular detection and quantification.

[11]  B. Chabner,et al.  Application of Cell-free DNA Analysis to Cancer Treatment. , 2018, The New England journal of medicine.

[12]  Jan Kremláček,et al.  Changes in circulating cell-free DNA and nucleosomes in patients with exacerbated psoriasis , 2017, Archives of Dermatological Research.

[13]  I. Brandslund,et al.  Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. , 2017, The oncologist.

[14]  P. B. Gahan,et al.  Origins, structures, and functions of circulating DNA in oncology , 2016, Cancer and Metastasis Reviews.

[15]  D. Trisciuoglio,et al.  Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies , 2016, Aging.

[16]  C. Caldas,et al.  Cell‐free circulating tumour DNA as a liquid biopsy in breast cancer , 2016, Molecular oncology.

[17]  R. Cowan,et al.  Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  A. Kalmár,et al.  Cell Free DNA of Tumor Origin Induces a ‘Metastatic’ Expression Profile in HT-29 Cancer Cell Line , 2015, PloS one.

[19]  N. Tunariu,et al.  Serial Next-Generation Sequencing of Circulating Cell-Free DNA Evaluating Tumor Clone Response To Molecularly Targeted Drug Administration , 2015, Clinical Cancer Research.

[20]  Y. Wu,et al.  Circulating cell-free DNA in serum as a biomarker for diagnosis and prognostic prediction of colorectal cancer , 2014, British Journal of Cancer.

[21]  M. Choti,et al.  Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies , 2014, Science Translational Medicine.

[22]  P. Gahan.  Circulating nucleic acids in plasma and serum: roles in diagnosis and prognosis in diabetes and cancer. , 2008, Infectious disorders drug targets.

[23]  Nicola Pimpinelli,et al.  WHO-EORTC classification for cutaneous lymphomas. , 2005, Blood.

[24]  M. Girardi,et al.  Mycosis Fungoides and Sezary Syndrome. , 2017, Hematology/oncology clinics of North America.

[25]  V. Vasioukhin,et al.  The Origin and Mechanism of Circulating DNA , 2000, Annals of the New York Academy of Sciences.

[26]  M. Weinstock,et al.  Twenty-year trends in the reported incidence of mycosis fungoides and associated mortality. , 1999, American journal of public health.

[27]  R. Hay,et al.  The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. III. Independent hospital validation , 1994, The British journal of dermatology.

[28]  R. Martí,et al.  Prognostic clinicopathologic factors in cutaneous T-cell lymphoma. , 1991, Archives of dermatology.

[29]  N. Onsun,et al.  Prognostic Evaluation of Neutrophil/Lymphocyte Ratio in Patients with Mycosis Fungoides. , 2017, Annals of clinical and laboratory science.

[30]  P. Nizard,et al.  Assessment of DNA Integrity, Applications for Cancer Research. , 2015, Advances in clinical chemistry.

[31]  M. Fleischhacker,et al.  Circulating nucleic acids (CNAs) and cancer--a survey. , 2007, Biochimica et biophysica acta.

[32]  Koichiro Nakamura,et al.  Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides. , 2003, Journal of the American Academy of Dermatology.

[33]  E. Vonderheid,et al.  Increased serum concentration of the soluble interleukin-2 receptor in cutaneous T-cell lymphoma. Clinical and prognostic implications. , 1996, Archives of dermatology.

[34]  W. Youden,et al.  Index for rating diagnostic tests , 1950, Cancer.