Abstract 2782: MicroRNAs response to concurrent chemoradiotherapy predicts oligo- and polymetastatic progression in patients with Stage IV colorectal adenocarcinoma

Abstract

Abstract Colorectal cancer (CRC) is the third most common cancer and an important contributor to cancer mortality and morbidity worldwide. The survival rate (11%) in patients with stage IV CRC remain suboptimal. Among these, an intermediate state of distal metastasis termed oligometastasis(es) is characterized by a less aggressive biology with limited tumor progression. Oligometastases are amenable to metastasis-directed local treatments; however, a significant portion of these progresses to polymetastases. The purpose of this study is to identify predictors of oligometastatic progression that could improve patient selection and survival for metastasis-directed localized therapy. microRNAs (miRs) classifiers have previously been shown to predict oligometastatic progression in smaller studies with a heterogeneous primary tumor. Here, we focus on a larger and first study comprising exclusively stage IV CRC to determine CRC-specific classifier of oligometastic progression. We analyzed microRNAs microarray expression patterns from initial oligometastatic patients (≤5 initial metastases) with metastatic CRCs resected with curative intent. 96 stage IV CRC Korean subjects (70 males, 26 females; mean age 60 years) were stratified into subgroups based on their rate of recurrent metastatic progression over a follow-up period. The criteria for these subgroups were previously validated (PloS one, 7(12), p.e50141): (i) patients with no and/or low rate of progression (LRP; <0.6 new metastases/year) and (ii) patients with a high rate of progression (HRP; >3.6 new metastases/year). microRNA expression (Affymetrix GeneChip microRNA 4.0) was analyzed with quantile normalization, COMBAT, and LIMMA, and then validated using PAM. 47 microRNAs were prioritized (FDR<5%) between HRP (n=22) and LRP (n=60) and were associated with the rate of metastatic progression and survival in the current dataset. Six miroRNAs of this study were previously shown to discriminate between HRP vs LRP among lung metastases of heterogeneous primary tumor types (miR-127-5p, miR-154-5p, miR-199b-5p, miR-485-5p, miR-491-5p, and miR-502-5p). In addition, we observe an overrepresentation of microRNAs from the 14q32.31 locus and members of the miR-154 family from this loci that had previously been implicated in oligo- vs poly- metastasis progression (miR-154-5p, miR-337-5p, miR-381-3p, miR-382-5p, miR-409-5p, and miR-487a-3p). These results further corroborate the hypothesis that HRP and LRP are distinct entities at both clinical and molecular levels. Citation Format: Sung Hak Lee, Nima Pouladi, Colleen Kenost, Francesca Vitali, Yves A. Lussier. MicroRNAs response to concurrent chemoradiotherapy predicts oligo- and polymetastatic progression in patients with Stage IV colorectal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2782.