Identification of a Plasma Four-microRNA Panel as Potential Noninvasive Biomarker for Osteosarcoma

Abstract

BackgroundCirculating microRNAs (miRNAs) are emerging as promising biomarkers for human cancer. Osteosarcoma is the most common human primary malignant bone tumor in children and young adults. The objective of this study was to investigate whether circulating miRNAs in plasma could be a useful biomarker for detecting osteosarcoma and monitoring tumor removal dynamics.MethodsPlasma samples were obtained from 90 patients before surgery, 50 patients after one month of surgery, and 90 healthy individuals. The study was divided into three steps: First, initial screening of the profiles of circulating miRNAs in pooled plasma samples from healthy controls and pre-operative osteosarcoma patients using a TaqMan low density array (TLDA). Second, evaluation of miRNA concentration in individual plasma samples from 90 pre-operative osteosarcoma patients and 90 healthy controls by a quantitative real time PCR (qRT-PCR) assay. Third, evaluation of miRNA concentration in paired plasma samples from 50 pre- and post-operative osteosarcoma patients by qRT-PCR assay.ResultsFour plasma miRNAs including miR-195-5p, miR-199a-3p, miR-320a, and miR-374a-5p were significantly increased in the osteosarcoma patients. Receiver operating characteristics curve analysis of the combined populations demonstrated that the four-miRNA signature could discriminate cases from controls with an area under the curve of 0.9608 (95% CI 0.9307-0.9912). These 4 miRNAs were markedly decreased in the plasma after operation. In addition, circulating miR-195-5p and miR-199a-3p were correlated with metastasis status, while miR-199a-3p and miR-320a were correlated with histological subtype.ConclusionsOur data suggest that altered levels of circulating miRNAs might have great potential to serve as novel, non-invasive biomarkers for osteosarcoma.

LINC00473/miR‐374a‐5p regulates esophageal squamous cell carcinoma via targeting SPIN1 to weaken the effect of radiotherapy

“…miRNAs, recognized as a class of endogenous small noncoding RNAs at 19 to 25 nucleotides of length, can regulate the expression of their target genes via targeting the 3ʹ‐untranslated region (3′UTR) of messenger RNAs, resulting in translational repression or degradation of mRNAs . Among them, downregulation of miR‐374a‐5p has been discovered in various cancers . Nevertheless, its role in ESCC remains to be investigated.…”

Molecular mechanisms and microRNAs in osteosarcoma pathogenesis

“…In contrast to healthy individuals, osteosarcoma patients display increased contents of miR 148a, miR 195 5p, miR 199a 3p, miR 320a, miR 374a 5p, miR 196a, miR 196b, and miR 21 [55,60,63,76,77] in plas ma and/or serum. After surgical removal of the tumors, the concentrations of miR 195 5p, miR 199a 3p, miR 320a, and miR 374a 5p in blood considerably decrease [63].…”

“…The serum levels of miR 21, miR 143, miR 199a 3p, and miR 320a correlate with the histological type of osteosarcoma [55,63]. Thus, the osteoblastic type is characterized by increased contents of miR 21 and miR 320a and by decreased contents of miR 143 and miR 199a 3p [55,65].…”

“…However, the data on miR 195 are contradictory. According to [63], miR 195 is upregulated in osteosarcoma. However, it has been shown [62] that increase in the levels of this miRNA inhibits cell migration and invasion in both cell cultures and clinical samples.…”

“…After surgical removal of the tumors, the concentrations of miR 195 5p, miR 199a 3p, miR 320a, and miR 374a 5p in blood considerably decrease [63].…”