Differential miRNA Expression in Neuroendocrine Tumours of the Lung

Background: Four neuroendocrine subtypes are distinguishable which differ in the extent of differentiation and grade of biological aggressiveness. Therefore the differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. However, for pathologists it is often a challenge to establish a faithful differenzial diagnosis with an accurate prognosis which is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts. Thus we investigated three types of miRNAs as an additional tool for differential diagnosis and possible molecular targets.

Materials and Methods: A collective of 38 patients suffering from well to poorly differentiated neuroendocrine lung tumours were examined. Three different miRNAs (miR-21, miR-34a and miR-155) were investigated in four distinct subtypes of pulmonary neuroendocrine tumours by comparative gene expression analysis.

Results: miR-21 expression was increased in high grade neuroendocrine tumours (p < 0.000). In contrast miR-34a showed high expression values in low grade neuroendocrine carcinomas (p = 0.008). In case of miR-155, a tendency towards increased expression levels in high grade tumours is predictable.

Conclusions: miRNAs seem to play important roles in tumorgenesis of neuroendocrine tumours of the lung. A close association is implicated between the elevated miR-21 in high-grade and miR-34a in low grade NE lung carcinomas which could potentially be exploited as practical biomarkers for early and differential lung cancer diagnosis. However, some additional research and validation studies are needed to utilize them as routine markers or potential targets for personalized medicine.