Abstract
Angiogenesis is a critical event in the development, progression, and spread of various human cancers, including lung cancer. Molecular mechanisms that underlie the complex regulation of angiogenic processes are poorly understood. However, an increasing body of evidence indicates miRNAs as important regulators of tumor angiogenesis. Forceps biopsies were collected from tumor tissue, surrounding tissue, and non-tumor tissue from 50 NSCLC patients. Lung tissue samples from individuals with no clinical evidence of a cancerous disease served as controls. Immunohistochemical staining for Factor VIII was used to evaluate microvessel density (MVD). TaqMan® primer-probe sets were used in quantitative real-time RT-PCR reactions to determine expression levels of let-7b, miR-126, miR-9, and miR-19a. We demonstrated significantly higher MVD and decreased expression levels of let-7b and miR-126 in tumor tissue and surrounding tissue in comparison to corresponding non-tumor tissue or lung tissue from the control group. In addition, no differences in MVD and expression levels of both miRNAs between tumor tissue and surrounding tissue from NSCLC patients were observed. Low expression of both miRNAs correlated with high MVD and worse progression-free survival and overall survival. These observations strongly suggest similar molecular alternations within tumor tissue and surrounding tissue that comprise a specific microenvironment. Low expression of let-7b and miR-126 seems to have a possible anti-angiogenic role in lung tumor tissue and significantly correlates with worse survival outcomes for lung cancer patients. Moreover, the regulation of let-7b and miR-126 expression could have therapeutic potential because it could reduce tumor angiogenesis and therefore suppress tumor growth in lung cancer patients.
Highlights
Lung cancer, the leading cause of cancer-related deaths worldwide, is frequently diagnosed in its advanced stage; chemotherapy combined with thoracic radiotherapy represents the mainstay of treatment
No differences in microvessel density (MVD) were observed between tumor tissue and surrounding tissue or when patients were stratified according to stage of disease, type of lung cancer or sex
Molecular mechanisms that underlie the complex regulation of tumor angiogenesis are poorly understood
Summary
The leading cause of cancer-related deaths worldwide, is frequently diagnosed in its advanced stage; chemotherapy combined with thoracic radiotherapy represents the mainstay of treatment. A therapy that interferes with specific molecular targets holds great promise in improving clinical outcomes in lung cancer treatment [1,2]. A developing solid tumor is generally in an oxygen-starved or hypoxic state, which triggers the differential expression of mediators that either promote or suppress angiogenesis [3]. Angiogenic factors (e.g., the family of vascular endothelial growth factors [VEGFs] and their receptors) controlling this complex process have been the focus of efforts to identify novel therapeutic targets and to develop treatment strategies in order to inhibit angiogenesis and suppress the uncontrolled proliferation of developing tumors [2]. Elucidating the molecular mechanisms that regulate angiogenesis could be of great importance in reducing cancer-related mortality [3,4]
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