NOVEL SERUM CIRCULATING MIRNAS SIGNATURES FOR NSCLC TREATMENT OUTCOME


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Julija Fadejeva1,Diana Schveigert2,Saulius Cicenas2,Kestutis Suziedelis1
1National Cancer Institute; Faculty of Natural Sciences, Vilnius University Joint Life Sciences Center,2National Cancer Institute

Abstract

Background

Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related deaths worldwide. The growth of NSCLC mortality rates is associated with a lack of significant biomarkers for early cancer detection and treatment outcome. Advances in the molecular oncology have resulted in the discovery of potential, novel molecular biomarkers with predictive value. Results from our previous studies indicate that miR-181a expression in the tumor is associated with NSCLC tumor differential grade and miR-630 − with disease progression after adjuvant chemotherapy. The aim of this study was to determine the expression of circulating miR-181a and miR-630 in NSCLC serum samples and its association with response to treatment.

Method

A total of 40 NSCLC patients and 10 healthy controls were enrolled to the study. None of the patients had preoperative chemotherapy. Circulating miRNA was extracted from frozen serum using “miRNeasy Mini Kit” (QIAGEN, Germany). Analysis of miR-181a and miR-630 was done by qRT-PCR using TaqMan® MicroRNA Assays (Applied Biosystems, USA). miRNAs expression was determined relatively to the expression of internal control RNU6B and analyzed by 2-∆∆Ct method.  A χ2 test was used to evaluate association between miRNAs expression, clinicopathological parameters and response to treatment.

Results

Statistically significant differences were found between miR-630 expression and response to treatment with cisplatin of NSCLC patients. High miR-630 expression was identified more often in patients with stable disease (p=0,03). Moreover, there are trends in the association between miR-181a and a disease stage. High miR-181a expression is more common for patient with early (I/II) NSCLC stages (p=0,08).

Conclusion

The slower disease progression is expected for NSCLC patients with high miR-630 expression in serum after surgery and cisplatin/etoposide treatment. Patients with low miR-630 expression should be followed-up more attentively due to possible rapid disease progression.