title: Monitoring the HER2 copy number status in circulating tumor DNA by droplet digital PCR in patients with gastric cancer.
abstract: BACKGROUND
  We previously demonstrated the potential of circulating tumor DNA (ctDNA) for the amplification of detecting HER2 in patients with gastric cancer (GC). In the present study, we focused on the clinical courses of patients who developed recurrence with GC, and investigated the potential clinical utility of the ddPCR-based HER2 copy number (CN) as a marker for the temporal and/or spatial heterogeneities of GC during treatment progress.
  
  
  METHODS
  We enrolled 30 healthy volunteers and 60 patients with GC who underwent surgery, including 17 patients who developed recurrence. Using ribonuclease P RNA component H1 (RPPH1) as a reference gene, plasma HER2 to RPPH1 ratios (the HER2 ratio) were determined using ddPCR.
  
  
  RESULTS
  The preoperative plasma HER2 ratio correlated with the tumor HER2 status (p < 0.001), and sensitivity and specificity were 0.733 and 0.933, respectively. Analyses of plasma samples during the postoperative follow-up periods revealed that high plasma HER2 ratios were detected at the time of recurrence in 7 of 13 cases, which were diagnosed as being HER2 negative at the time of surgery. These results were supported by continuously increasing HER2 ratios thereafter with the progression of recurrent cancer.
  
  
  CONCLUSIONS
  The plasma HER2 ratio determined by ddPCR is a repeatable and noninvasive approach for real-time evaluations of the HER2 status to monitor the effects of treatments for patients with HER2-positive GC and enable treatment options for patients with HER2-negative GC but positive conversion of the HER2 status after recurrence.
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.|Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Shoda
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan. ichikawa@koto.kpu-m.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.|Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Hiramoto
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.|Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hamada
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Arita
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Konishi
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Komatsu
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.affiliation: Department of Surgery, Kyoto Second Red Cross Hospital, 355-5 Haruobi-cho, Kamigyo-ku, Kyoto, 602-8026, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kakihara
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Surgery, Kyoto Second Red Cross Hospital, 355-5 Haruobi-cho, Kamigyo-ku, Kyoto, 602-8026, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan. issehgen@tokushima-u.ac.jp.
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000097:blood / Q000235:genetics / Q000556:secondary; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood / Q000235:genetics*; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: DdPCR; Gastric cancer; HER2; Liquid biopsy; ctDNA