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
490P - Outcomes of sequential epidermal growth factor receptor tyrosine (EGFR) tyrosine kinase inhibitor (TKI) therapy in patients with advanced non-small cell lung carcinoma (NSCLC)- a real-world institutional experience
Presenter: Yvonne Ang
Session: Poster display session
Resources:
Abstract
498P - An observational retrospective study to evaluate the incidence of acquired EGFR T790M resistance in NSCLC patients with EGFR mutation following progression after at least one prior EGFR TKI treatment in Taiwan: ARISE study
Presenter: Shang-gin Wu
Session: Poster display session
Resources:
Abstract
501P - Clinical characteristics and efficacy in non-small cell lung cancer patients with EGFR exon 20 insertion and EGFR amplification
Presenter: Xin Gao
Session: Poster display session
Resources:
Abstract
502P - Epidermal growth factor receptor tyrosine kinase inhibitor treatment response in advanced non-small cell lung cancer with uncommon mutations: A multicenter observational study
Presenter: Masaki Kanazu
Session: Poster display session
Resources:
Abstract
482P - Interim analysis from a phase IIIb, open-label study of afatinib in EGFR TKI-naïve patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC
Presenter: Filippo De Marinis
Session: Poster display session
Resources:
Abstract
483P - A phase IIIb, open-label study of afatinib in EGFR TKI-naïve patients with EGFR mutation-positive NSCLC: A biomarker analysis
Presenter: Rafael Rosell
Session: Poster display session
Resources:
Abstract
484P - Activity of afatinib in patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC and baseline brain metastases: Pooled analysis of three large phase IIIb trials
Presenter: Maya Gottfried
Session: Poster display session
Resources:
Abstract
491P - Clinical outcomes of leptomeningeal metastases in EGFR-mutant lung adenocarcinoma
Presenter: Chia-I Shen
Session: Poster display session
Resources:
Abstract
510P - Paclitaxel as continuation maintenance therapy in patients with advanced non-small cell lung cancer
Presenter: Suzy Gohar
Session: Poster display session
Resources:
Abstract
496P - Higher osimertinib introduction rate achieved by multiple repeated re-biopsy after acquired resistance to first/second generation EGFR-TKIs
Presenter: Taira Ninomaru
Session: Poster display session
Resources:
Abstract