Comparisons of microRNA Patterns in Plasma before and after Tumor Removal Reveal New Biomarkers of Lung Squamous Cell Carcinoma

Abstract

Lung cancer is the major human malignancy, accounting for 30% of all cancer-related deaths worldwide. Poor survival of lung cancer patients, together with late diagnosis and resistance to classic chemotherapy, highlights the need for identification of new biomarkers for early detection. Among different cancer biomarkers, small non-coding RNAs called microRNAs (miRNAs) are considered the most promising, owing to their remarkable stability, their cancer-type specificity, and their presence in body fluids. However, results of multiple previous attempts to identify circulating miRNAs specific for lung cancer are inconsistent, likely due to two main reasons: prominent variability in blood miRNA content among individuals and difficulties in distinguishing tumor-relevant miRNAs in the blood from their non-tumor counterparts. To overcome these impediments, we compared circulating miRNA profiles in patients with lung squamous cell carcinoma (SCC) before and after tumor removal, assuming that the levels of all tumor-relevant miRNAs would drop after the surgery. Our results revealed a specific panel of the miRNAs (miR-205, -19a, -19b, -30b, and -20a) whose levels decreased strikingly in the blood of patients after lung SCC surgery. Interestingly, miRNA profiling of plasma fractions of lung SCC patients revealed high levels of these miRNA species in tumor-specific exosomes; additionally, some of these miRNAs were also found to be selectively secreted to the medium by cultivated lung cancer cells. These results strengthen the notion that tumor cells secrete miRNA-containing exosomes into circulation, and that miRNA profiling of the exosomal plasma fraction may reveal powerful cancer biomarkers.

Genomewide Study of Salivary MicroRNAs for Detection of Oral Cancer

“…Jin et al (2013) highlighted the role of miRNA-27b overexpression mostly in progression of breast cancer rather than initiation. In addition, it has been shown that the profile of miRNAs in cancerous tissues and biofluids (e.g., plasma and serum) could be totally different and that miRNA secretion to the biofluid is a tightly specific controlled process (Boeri et al, 2011;Aushev et al, 2013). Consequently, OSCC cells may selectively release miRNA-27b into saliva, and this phenomenon results in significantly Curve of receiver operating characteristic and area under the curve.…”

The role of extracellular vesicle microRNAs in cancer biology

“…Several studies have shown that exosomal miRNAs can be detected in a variety of body fluids, from blood to breast milk, and that their levels are correlated with patient status [4,5,[60][61][62][63][64][65][66][67][68][69][70][71][72][73] (Table 1). On January 21, 2016, cancer diagnosis using exosomes from blood became commercially available in the US (http://www.exosomedx.com) [6].…”

MicroRNA-155-5p in pathogenesis of cancer

“…Примечательно, что при рецидивах рака легкого содержание miR-155 и miR-21 в экзосомах, полученных из плазмы, выше, чем у больных с первичными опухо-лями [57]. В нашем исследовании циркулирующих микроРНК, в том числе в экзосомах, не обнаружено различий уровня miR-155 в плазме пациентов с плоско-клеточным раком легкого после удаления первичного очага, однако большинство тестированных больных на момент операции не имели видимых метастазов [58]. К сожалению, количество работ, прицельно исследу-ющих miR-155 в метастазах или корреляции ее наличия в экзосомах с процессами формирования метастазов, ограничено.…”