616 - Early lymph node metastasis: altered microRNA expression in colon cancer

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Colon Cancer
Translational Research
Presenter Melanie Rammer
Authors M. Rammer1, H. Rumpold2, H. Bösmüller3, R. Marschon1, T. Malli1, W. Kranewitter1, M. Erdel1, S. Deutschbauer1, A.L. Petzer4, G. Webersinke1
  • 1Laboratory For Molecular Biology And Tumor Cytogenetics, Barmherzige Schwestern Hospital, Linz, 4010 - Linz/AT
  • 2Interne I:hematology, Medical Oncology And Gastroenterology, Krankenhaus der Barmherzigen Schwestern, AT-4040 - Linz/AT
  • 3Clinical Pathology, Barmherzige Schwestern Hospital, Linz, 4010 - Linz/AT
  • 4Interne I:hematology And Oncology, Krankenhaus der Barmherzigen Schwestern, AT-4040 - Linz/AT

Abstract

Recently several studies confirmed the regulatory potential of microRNAs (miRNAs). Via incomplete complementarity, miRNAs bind to mRNA targets thereby causing translational inhibition or target decay. Alterations of miRNA expression can be associated with various tumors. Furthermore, different miRNA levels were found to be linked with distinct tumor stages and could have a predictive and prognostic value, even regarding treatment response. The aim of the study is evaluating miRNÀs that correlate with early lymph node metastasis. Therefore, we compare formalin fixed, paraffin-embedded primary tissue of stage T4 colon tumors without lymph node metastasis with stage T1/2 tumors exhibiting lymph node metastasis. In order to initially scan for differentially expressed miRNAs, miRNA arrays (n = 8) were performed. A selection of miRNAs (miR-1207-5p, miR-146b-5p, miR-15a, miR-21, miR-494) showing distinct expression was then validated in a patient collective via RT qPCR. MiR-191 and miR-720 were chosen as endogenous controls, since they showed consistent expression in the preliminary array analysis. According to our array results, eight miRNAs displayed an elevated expression in T4 tumors without lymph node metastasis compared to three miRNAs higher expressed in the second group investigated. The significantly elevated expression (≥2-fold) was confirmed via RT qPCR for two (miR-146b-5p, miR-21) and one miRNA (miR-494), respectively. Some of our miRNA expression data correlates with that presented in studies regarding metastasis in colon cancer and other malignancies. Nevertheless, several miRNAs diverge compared to studies from other groups, e.g. miR-21. This could be due to differences in the tumor stages examined in these studies. To our knowledge, miRNA expression in the colon cancer stages investigated here has not been compared so far. To validate our findings concerning miRNA expression patterns in colon tumors associated with early lymph node metastasis, we will investigate a larger cohort. This further enhances our understanding of disease progression. Moreover, it implies the possibility of distinguishing stage and metastatic potential in biopsy specimen for novel therapeutic strategies.

Disclosure

All authors have declared no conflicts of interest.