5253 - Circulating microRNAs related to DNA damage response as predictors of survival in metastatic non- small cell lung cancer patients treated with platinum-based chemotherapy

Background

Aberrant miRNA expression has been associated with DNA damage response (DDR) pathways that modulate tumor response to platinum agents. We assessed the expression of miR-21, miR-128, mir-155 and miR-181 involved in DDR pathways, in the plasma of metastatic non- small cell lung cancer (mNSCLC) patients receiving 1^st-line platinum-based chemotherapy (CMT) and the levels were correlated with patients’ outcomes. We also performed bioinformatics analysis to identify putative target genes of the above miRNAs.

Methods

Plasma samples were obtained from patients (n = 128) before 1^st-line CMT. miR-21, miR-128, miR-155 and miR-181 expression levels were assessed by RT-qPCR and expression was classified as high or low according to the median values. Pathway analysis was performed by Diana-Tarbase algorithm.

Results

Mir-128 (p < 0.001), miR-155 (p < 0.001) and miR-181 (p = 0.012) were higher in mNSCLC patients compared to healthy donors. Patients with high miR-128 and miR-155 expression had shorter overall survival (OS) (p = 0.028 and p = 0.035, respectively). In multivariate analysis performance status of 2 and high miR-128 expression independently predicted for shorter OS in the whole group of patients (p = 0.003 and p = 0.026, respectively). No differences in miRNA expression were revealed among patients with adenocarcinoma (n = 79) and squamous carcinoma (SCC; n = 41). However, in the SCC subgroup, besides miR-128 and miR-155, high miR-21 and miR-181 expression were associated with shorter OS (p = 0.021, p = 0.015, p = 0.004 and p = 0.028, respectively). In multivariate analysis, miR-155 high expression independently predicted for decreased OS (p = 0.004). Integrated function and pathway analysis on miRNA predicted genes revealed that pathways related to cancer, cell cycle, apoptosis and drug resistance were significantly enriched.

Conclusions

Differential expression levels of DDR related miRNAs are encountered in mNSCLC patients before 1^st-line platinum-based CMT and independently predict patients’ outcomes. The association of miR-155 with the prognosis of patients with SCC merits further investigation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

HESMO.

Disclosure

All authors have declared no conflicts of interest.