Abstract
BackgroundMicroRNA (miR)-21 has been revealed as an oncogene in cancer development, and is one of the miRNAs closely connected to angiogenesis. We aimed to explore the impact of miR-21 expression in both tumor and stromal compartments of non-small cell lung cancer (NSCLC), and correlations between miR-21 and angiogenic protein markers.MethodsFrom 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarrays (TMAs). In situ hybridization (ISH) was used to detect the expression of miR-21 separately in tumor cells and stromal cells of the tumor, and immunohistochemistry (IHC) was used to detect the expression of the protein markers protein kinase B (Akt), phosphatidylinositol-3-kinase (PI3K), hypoxia induced factor 1 (HIF1α) and vascular endothelial growth factor-A (VEGF-A).ResultsIn univariate analyses, high tumor cell expression of miR-21 in patients with lymph node metastasis was a positive prognostic factor (P = 0.024). High stromal miR-21 expression had a negative prognostic impact (P = 0.022). In the multivariate analysis, low tumor mir-21 expression in node positive patients was an independent adverse prognostic factor (HR 2.03, CI 95% 1.09-3.78, P = 0.027).ConclusionsIn patients with lymph node metastasis, miR-21 expression in tumor cells is an independent positive prognostic factor. High stromal miR-21 expression is a negative prognostic factor.
Highlights
MicroRNA-21 has been revealed as an oncogene in cancer development, and is one of the miRNAs closely connected to angiogenesis
In this study we aimed to investigate the prognostic impact of miR-21 in a large unselected non-small cell lung cancer (NSCLC) population
Low tumor miR-21 expression was an independent negative prognostic factor (HR 2.03, CI 95% 1.09-3.78, P = 0.027)
Summary
MicroRNA (miR)-21 has been revealed as an oncogene in cancer development, and is one of the miRNAs closely connected to angiogenesis. Studies have revealed miR-21 as an oncogene [5], and in a recent meta-analysis miR-21 appeared as a negative prognostic factor [2] It is one of the miRNAs closely connected to angiogenesis [6,7]. In a recent study [8], we screened tissues from 10 worst and 10 best prognosis NSCLC cases as well as 10 controls for the expression of several angiogenesis-related miRNAs. miR21 was significantly up-regulated in tumor versus normal tissue, and was among the miRNAs with the largest expression difference between tumor tissue and normal samples. Though recent studies on its influence on angiogenesis suggest both pro- and antiangiogenic properties [9,10], the involved mechanisms remains to be further investigated
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