Abstract 134P
Background
Although endoscopic surveillance remains the gold standard for diagnosing asymptomatic gastric cancer (GC) patients, associated costs and its invasive nature render it inadequate as a screening approach. Development of less invasive tests is needed for surveillance of early stage GCs. Over the last decade, tumor-derived miRNAs in peripheral blood are emerging as promising disease biomarkers. Herein we have conducted a comprehensive miRNA expression profiling, followed by bioinformatic analysis to establish a novel serum-based miRNA signature for the diagnosis of patients with GC.
Methods
We analyzed tissue miRNA expression profiles in three patient cohorts (n = 602) in an in-silico discovery step, during which the robustness of candidate biomarkers was tested and validated. The performance of this miRNA signature was evaluated in a serum training cohort (n = 327). Using a logistic regression model, the panel was further refined, and this circulating miRNA signature was validated in two prospective cohorts (n = 174, 175).
Results
Genome-wide analysis of miRNA expression data resulted in identification of 10-miRNAs that distinguished cancer tissues from normal mucosa in three independent datasets (AUC = 0.984, 0.939 and 1.000). Using a serum training cohort, the miRNA candidates were further refined to six-circulating-miRNA signature. This miRNA signature demonstrated a robust diagnostic value in the training cohort. Subsequently we demonstrated robustness of the signature in two prospective cohorts (AUC = 0.87, 0.86). Remarkably, the 6-circulating-miRNA signature was able to detect early stage GC patients robustly (AUC = 0.855). Furthermore, the signature was significantly superior at identifying patients with GC to conventional tumor markers, CEA (P = 0.0001) and CA19-9 (P = 0.0001).
Conclusions
Using a comprehensive data analysis followed by substantial clinical validations, involving over 1600 GC tissue and serum specimens across 7 independent cohorts, we developed a novel 6-circulating-miRNA signature, which demonstrated an unprecedented diagnostic value and a great promise for early non-invasive detection of GC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Daisuke Izumi.
Funding
NIH.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
107P - The efficacy of adjuvant chemotherapy according to the risk classification of recurrence based on the systemic inflammatory markers in patients with colorectal cancer liver metastases
Presenter: Masatsune Shibutani
Session: Poster display session
Resources:
Abstract
108P - Influence of liver metastasis locations on overall survival in patients with colorectal cancer
Presenter: Takayuki Sone
Session: Poster display session
Resources:
Abstract
109P - 18F-FDG PET/CT textural features as predictors of outcomes in patients with primary advanced colorectal cancer
Presenter: Jing Yang
Session: Poster display session
Resources:
Abstract
110P - D3 lymph node dissection may be necessary in clinical stage I right colon cancer
Presenter: Woong Bae Ji
Session: Poster display session
Resources:
Abstract
111P - Is preoperative chemoradiotherapy necessary for all patients with upper rectal cancer: One center retrospective study
Presenter: Jasur Madyarov
Session: Poster display session
Resources:
Abstract
112P - A retrospective analysis of the association between perioperative, post adjuvant carcinoembryonic antigen level and prognosis in stage III colorectal cancer
Presenter: Ryotaro Kozuki
Session: Poster display session
Resources:
Abstract
113P - Dicer contributes to chemoresistance in colorectal cancer via regulating a set of miRNAs and their downstream mRNAs
Presenter: Liang-Yi Hung
Session: Poster display session
Resources:
Abstract
114P - Efficacy and safety of the combination of bevacizumab with raltitrexed-based chemotherapy as second-line therapy in patients with metastatic colorectal cancer (mCRC): An interim analysis of a multicenter phase II trial
Presenter: Jun Zhu
Session: Poster display session
Resources:
Abstract
115P - Expression of Ki-67 as a prognostic factor in patients with colorectal cancer
Presenter: Kuantkan Zhabagin
Session: Poster display session
Resources:
Abstract
116P - Clinical significance and converionrate relevance of RAS genetic mutation analysis for unresectable colorectal liver metastases: A single-center retrospective study
Presenter: Meiling Ji
Session: Poster display session
Resources:
Abstract