BACKGROUND: This study was designed to evaluate the clinical benefit of predicting the cyclin D1 (CCND1) status using cell-free plasma DNA in superficial esophageal squamous cell carcinoma (ESCC) patients. METHODS: The ratio of the CCND1 (11q13) dosage to the DRD2 (11q22-23) dosage (C/D ratio) as the CCND1 copy number was evaluated. This study was divided into three steps: (1) demonstration of the feasibility, (2) evaluation of whether the plasma C/D ratio assay could monitor tumor dynamics, and (3) a validation study in 63 consecutive superficial ESCC (pTis-T1) patients and 40 healthy volunteers. RESULTS: (1) The plasma C/D ratio was significantly higher (p = 0.0369) in superficial ESCC patients than in the controls in a preliminary test. (2) The high plasma C/D ratio appeared to reflect the tumor levels of the CCND1 status and was reduced in postoperative plasma samples (p = 0.1154) and samples following endoscopic resection (p = 0.0845). (3) Validation analysis revealed that the plasma C/D ratio was significantly higher in superficial ESCC patients than in controls (p < 0.0001). The frequency of recurrence was significantly higher (p = 0.0198), and recurrence-free survival was significantly shorter (p = 0.0075) in patients with a high plasma C/D ratio. Moreover, a high C/D ratio was shown to be an independent risk factor for recurrence on multivariate analysis [p = 0.0334; odds ratio 10.58 (range 1.203-93.23)]. CONCLUSION: The prediction of CCND1 amplification by plasma DNA may be a new complementary clinical biomarker for recurrence in patients with superficial ESCC.
BACKGROUND: This study was designed to evaluate the clinical benefit of predicting the cyclin D1 (CCND1) status using cell-free plasma DNA in superficial esophageal squamous cell carcinoma (ESCC) patients. METHODS: The ratio of the CCND1 (11q13) dosage to the DRD2 (11q22-23) dosage (C/D ratio) as the CCND1 copy number was evaluated. This study was divided into three steps: (1) demonstration of the feasibility, (2) evaluation of whether the plasma C/D ratio assay could monitor tumor dynamics, and (3) a validation study in 63 consecutive superficial ESCC (pTis-T1) patients and 40 healthy volunteers. RESULTS: (1) The plasma C/D ratio was significantly higher (p = 0.0369) in superficial ESCC patients than in the controls in a preliminary test. (2) The high plasma C/D ratio appeared to reflect the tumor levels of the CCND1 status and was reduced in postoperative plasma samples (p = 0.1154) and samples following endoscopic resection (p = 0.0845). (3) Validation analysis revealed that the plasma C/D ratio was significantly higher in superficial ESCC patients than in controls (p < 0.0001). The frequency of recurrence was significantly higher (p = 0.0198), and recurrence-free survival was significantly shorter (p = 0.0075) in patients with a high plasma C/D ratio. Moreover, a high C/D ratio was shown to be an independent risk factor for recurrence on multivariate analysis [p = 0.0334; odds ratio 10.58 (range 1.203-93.23)]. CONCLUSION: The prediction of CCND1 amplification by plasma DNA may be a new complementary clinical biomarker for recurrence in patients with superficial ESCC.
Authors: Frank Diehl; Kerstin Schmidt; Michael A Choti; Katharine Romans; Steven Goodman; Meng Li; Katherine Thornton; Nishant Agrawal; Lori Sokoll; Steve A Szabo; Kenneth W Kinzler; Bert Vogelstein; Luis A Diaz Journal: Nat Med Date: 2007-07-31 Impact factor: 53.440
Authors: Luis A Diaz; Richard T Williams; Jian Wu; Isaac Kinde; J Randolph Hecht; Jordan Berlin; Benjamin Allen; Ivana Bozic; Johannes G Reiter; Martin A Nowak; Kenneth W Kinzler; Kelly S Oliner; Bert Vogelstein Journal: Nature Date: 2012-06-28 Impact factor: 49.962
Authors: Tej D Azad; Aadel A Chaudhuri; Penny Fang; Yawei Qiao; Mohammad S Esfahani; Jacob J Chabon; Emily G Hamilton; Yi D Yang; Alex Lovejoy; Aaron M Newman; David M Kurtz; Michael Jin; Joseph Schroers-Martin; Henning Stehr; Chih Long Liu; Angela Bik-Yu Hui; Viren Patel; Dipen Maru; Steven H Lin; Ash A Alizadeh; Maximilian Diehn Journal: Gastroenterology Date: 2019-11-09 Impact factor: 22.682