miRNA Biomarkers in Lung Cancer
Let-7, a natural and separately transcribed miRNA maps to a chromosomal region associated with lung cancer as a regulator of Ras expression. Let-7 expression is lower in lung tumors than in normal lung tissue, while RAS protein is significantly higher in lung tumors, providing a possible mechanism for let-7 in cancer. The let-7 miRNA regulates Ras by binding to the message for Ras and likely inhibits translation of the Ras protein rather than revertion of a mutated Ras to normal. The LCS6 variant allele in a KRAS miRANA complementary site is significantly associated with increased risk for NSCLC among moderate smokers and links let-7 miRNAs to lung cancer susceptibility (Chin et al. 2008). These findings opens up the possibility that gene therapy with let-7 may alleviate or slow down lung cancer.
Studying current and non-smokers, researchers from Boston University School of Medicine have examined whole-genome miRNA and mRNA expression in bronchial airway epithelial brushings obtained at bronchoscopy and found 28 miRNAs to be differentially expressed in the majority of smokers. In addition, they showed that modulating the expression of one of these miRNAs, mir-218, was sufficient to alter the expression of a subset of the mRNAs that are both predicted targets of this miRNA and altered by smoking in vivo. These studies suggest that smoking- dependent changes in miRNA expression levels mediate some of the smoking induced gene expression changes in airway epithelium and that miRNAs therefore play a role in the host response to environmental exposures and may contribute to the pathogenesis of smoking-related lung cancer. It is hoped that miRNA profiles obtained from these cells may serve as relatively noninvasive biomarkers for smoking-related lung diseases.
A study has explored miRNA expression profiles of lung tumors, normal lung tissues and plasma samples from cases with variable prognosis identified in a completed spiral-CT screening trial with extensive follow-up (Boeri et al. 2011). miRNA expression patterns significantly distinguished: (i) tumors from normal lung tissues; (ii) tumor histology and growth rate; (iii) clinical outcome; and (iv) year of lung cancer CT detection. Thus miRNAs play a role in lung tissues and plasma as molecular predictors of lung cancer development and aggressiveness and have theoretical and clinical implication for lung cancer management. The diagnostic ability of different miRNA biomarkers varies among reported studies. A systematic review has used diagnostic values analysis to summarize the overall test performance of miR- NAs (Huang et al. 2014). The results indicate that miRNAs in body fluids accurately identify NSCLC and are useful for diagnosis.