Usefulness of MicroRNAs as Prognostic Factors in Early Stage Non Small Cell Lung Carcinoma (NSCLC)
Jose Ramirez, Marc Campayo, Maria Luisa Cabanas, Nuria Vinolas, Ramon Marrades, Laureano Molins, Mariano Monzo. Hospital Clinic. IDIBAPS, CIBERES. Universitat de Barcelona, Barcelona, Spain; Universitat de Barcelona, Barcelona, Spain
Background: The transcription factor SOX2 is overexpressed in many solid tumours, including NSCLC. miR-145 and the miR-302-367 cluster are involved in stemness through SOX2 regulation. miR-145 plays an important role in SOX2 translation, and SOX2 regulates the expression of the miR-302-367 cluster. We have analyzed the expression of miR-145 and the miR-302-367 cluster in tumour and paired normal tissue samples from resected NSCLC patients and correlated our findings with time to recurrence (TTR).
Design: We analyzed the expression of miR-145 and miR-302-367 cluster in 70 tumour and 70 paired normal tissue samples from NSCLC patients who had undergone complete surgical resection from 2007 to 2009. We focused in 36 Adenocarcinoma and 28 Squamous Cell Carcinoma. RNA was obtained from fresh frozen tumour and normal tissue using the Trizol method and microRNA expression was detected using TaqMan MicroRNA Assays.
Results: Patients(p) characteristics: stage I, 12 (17.1%) stage II, 14 (20%) stage III; 36 (51.4%). 36 (51.4 %) Adenocarcinoma (ADC), 28 (40%) squamous cell carcinoma (SCC) 6 (8.6 %) NSCLC NOS. With a mean follow-up of 17 months (m), 23 p (32.9%) had relapsed. miR-145 expression was downregulated (P<0.001), and miR-367 expression was upregulated (P<0.001) in tumour compared to normal tissue samples. Mean TTR for p with low miR-145 levels was 18.4 m vs 28.2 m for p with high miR-145 (P=0.015). Mean TTR for p with low miR-367 levels was 29.1 m vs 23.4 m for p with high miR-367 (P=0.048). Concerning the prognostic differences between the main histological types, there was no correlation between the overexpression of both miRNAs in ADC cases. Conversely, there was a significant prognostic value of miR-367 for TTR (p=0.012) in SCC cases, but it was just a trend with miR-145 (p=0.071) for TTR.
Conclusions: In our study we have demonstrated a relationship between expression of miR-145 and miR-367 and TTR in SCC patients. On the other hand these microRNAs have no prognostic significance in ADC patients. Both conclusions support the importance of distinguishing SCC and ADC cases in all the studies with miRNAs.
Supported by a grant from F.I.S - 080135
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 311, Tuesday Morning