Evaluation of Plasma miR-21 and miR-152 as Diagnostic Biomarkers for Common Types of Human Cancers

Abstract

Stable blood based miRNA species have allowed for the differentiation of patients with various types of cancer. Therefore, specific blood-based miRNA might be considered as a methodology which could be informative of the presence of cancer potentially from multiple distinct organ sites. Recently, miR-21 has been identified as an “oncomir” in various tumors while miR-152 as a tumor suppressor. In this study, we investigated whether circulating miR-21 and miR-152 can be used for early detection of lung cancer (LuCa), colorectal carcinoma (CRC), breast cancer (BrCa) and prostate cancer (PCa), with distinguishing cancer from various benign lesions on these organ sites. We measured the two miRNA levels by using real-time RT-PCR in plasma samples from a total of 204 cancer patients, 159 various benign lesions, and 228 normal subjects. We observed significantly elevated expression of miR-21 and miR-152 in LuCa, CRC, and BrCa when compared with normal controls. We also found upregulation of plasma miR-21 and miR-152 levels in patients with benign lesions of lung and breast, as compared to normal controls, respectively. No significant expression variation of the two miRNAs was observed in PCa or prostatic benign lesions as compared to healthy controls. Receiver operating characteristic (ROC) analyses revealed that miR-21 and/or miR-152 can discriminate LuCa, CRC and BrCa from normal controls. Our results suggest that plasma miR-21 and miR-152 may serve as non-specific noninvasive biomarkers for early screening of LuCa, CRC, and BrCa, but not PCa.

Specific miRNA Disease Biomarkers in Blood, Serum and Plasma: Challenges and Prospects

“…One study specifically reports up-regulation of miR-155 in patients with metastases [53]. Independent studies show elevated levels of miR-21 in the serum ( [54,55]) and plasma of patients with breast cancer [31,33] or NSCLC [56][57][58]. Another reproduced miRNA-disease association was found between up-regulated miR-199a-3p and gastric cancer [59,60].…”

“…As miR-21 is involved in many diseases, the serum level of this miRNA has been recognized as a potential broad-spectrum biomarker for the detection of solid cancers [31,36]. Our literature review indicates that miR-21 may even serve as a general disease marker, for not only cancer but also non-cancer diseases.…”

“…Furthermore, we found diverging results with respect to miR-21 in prostate cancer. While plasma levels of this miRNA were reported to be up-regulated in prostate cancer [34,35], an independent study identified miR-21 as a non-specific noninvasive biomarker for lung cancer, colorectal carcinoma, and breast cancer but explicitly not for prostate cancer [31] (see also Fig. 3).…”

“…Manuscripts reporting on miR-21 described up-regulation in the plasma of patients with vulnerable coronary artery disease [23]; up-regulation in the serum or plasma of patients with RA [18]; up-regulation in the serum of patients with stroke or arteriosclerosis [24]; up-regulation in the serum of patients with COPD [25]; down-regulation in the plasma of patients with type 2 DM [26]; up-regulation in the plasma of patients with pediatric type 1 DM [27]; lack of dysregulation in the plasma of patients with type 2 DM (following adjustment for confounding variables such as age, sex, and others) [28]; up-regulation in the serum of patients with non-alcoholic fatty liver disease [29]; up-regulation in the plasma of patients with RA [18]; up-regulation in the plasma of patients with lung cancer [20,30,31]; up-regulation in the plasma of patients with colorectal cancer [31,32]; up-regulation in the plasma of patients with breast cancer [31,33]; up-regulation in the plasma of patients with prostate cancer [34,35]; and no dysregulation in the plasma of patients with prostate cancer [31]. As miR-21 is involved in many diseases, the serum level of this miRNA has been recognized as a potential broad-spectrum biomarker for the detection of solid cancers [31,36].…”

Circulating MicroRNAs in Colorectal Cancer

“…Combined the above miRNAs, a unique serum or plasma expression profile of miR-15b, miR-17, miR-18a, miR-21, miR-23a-3p, miR-24, miR-142-3p, miR-142-5p, miR-195, miR-320a, miR-331, miR376c-3p, miR-423-5p, miR-532, miR-532-3p, miR-652 and miR-1290 could distinguish benign colorectal polyp or adenoma lesions from healthy controls with good accuracy or high AUC values [27][28][29][30][31][32][33]. High levels of circulating miR-34a, miR-152 and low miR-150 levels were associated with the distinguish of patients with polyps or adenomas from those with CRC (AUC from 0.537 to 0.904) [34]. Distinguish the polyp or adenoma group from the normal group and the benign lesions group is important to improve patient survival and facilitate cancer prevention through the detection and removal of polyps or adenomas.…”