114P - Circulating microRNAs and response to oncological and surgical therapy in patients with locally advanced gastric cancer

Background

Therapeutic management of locally advanced gastric cancer (LAGC) combines surgery with neo-adjuvant (NACT) and adjuvant chemotherapy (ACT). miRNAs have emerged as promising candidates for treatment efficacy prediction, hence, the present study aims at defining therapy response-specific profiles of circulating miRNAin LAGC.

Methods

A prospective cohort of 26 LAGC patients scheduled for NACT, surgery and ACT treatment was considered. Peripheral blood samples were collected prior to (preNACT) and after NACT (postNACT) as well as after tumor surgical excision and by completion of ACT (postACT). Patients were grouped according to Becker’s tumor regression grade criteria into responders (R;TRG1-2) and non-responders (NR;TRG3). Serum RNA was isolated with magnetic bead technology and relative expression levels of miR21a, mir19a, mir20a, miR30a & miR15a were determined by qRT-PCR.

Results

PreNACT profiles revealed expression differences between R and NR patient groups, with Responders characterized by elevated miR21a and, particularly, miR30a and miR15a expression levels as compared to NR. In response to NACT, miR15a & miR30a downregulation was the most distinguished difference defining Responders. R profile also showed a distinct upregulation of mir21a and elevation of the initially low levels of mir20a & mir19a. In contrast, NR showed NACT-dependent upregulation of all targets except miR19a. Interestingly, it was surgical depletion of primary tumor that first led to a marked activation of studied miRNAs in both R and NR patients, an upregulation found further augmented after ACT treatment. Nevertheless, postACT miR15a and miR30a levels in R remained substantially lower than in NR, evidence adding to their potential as chemosensitivity indicators.

Conclusions

This study aimed at monitoring the consequential to oncological and surgical therapy response-dependent expression patterns of a panel of circulating miR and, despite the small case series, revealed the potential of, particularly, miR15a and miR30a as chemosensitivity predictors in LAGC. The evidence merits further investigation in larger patient cohorts to validate their clinical utility as biomarkes for stratifying GC patients for precision therapy.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

National and Kapodistrian University of Athens, Greece.

Funding

ERAPerMed 2019-GRAMMY ERA Per Med - Joint Transnational Call for Proposals (2019) for “Personalised Medicine: Multidisciplinary Research Towards Implementation”.

Disclosure

All authors have declared no conflicts of interest.