miR-144-3p as a novel plasma diagnostic biomarker for clear cell renal cell carcinoma

Urol Oncol. 2017 Jan;35(1):36.e7-36.e14. doi: 10.1016/j.urolonc.2016.07.012. Epub 2016 Sep 12.

Abstract

Objectives: Clear cell renal cell carcinoma (ccRCC) is the most frequent and lethal subtype of renal cell carcinoma, whose most effective measure of curing remains diagnosis and nephrectomy in its early phase. However, there is no feasible and recognized plasma biomarker for the clinical diagnosis of ccRCC. The objective of this study is to identify a novel plasma microRNA (miRNA) acting as an efficient diagnostic plasma biomarker in ccRCC.

Methods and materials: The plasma miRNA expression profile was quantified by miRNA microarray. Validation of miRNA levels of plasmas and tissues were performed by quantitative reverse transcription polymerase chain reaction in 106 ccRCC, 28 renal angiomyolipomas (AML), and 123 healthy control plasmas and in 110 ccRCC tissues.

Results: We found that plasma miR-144-3p levels in 106 ccRCC plasmas were remarkably up-regulated compared with that in healthy individuals and in patients with AML. miR-144-3p served as a promising plasma biomarker for yielding an area under the receiver operating characteristic curve of 0.91 with 87.10% sensitivity and 83.02% specificity in discriminating ccRCC from healthy individuals, and an area under the curve of 0.82 with 75.00% sensitivity and 71.70% specificity in discriminating ccRCC from patients with AML. In addition, plasma miR-144-3p levels were significantly decreased after surgery in 106 patients with ccRCC. Next, we examined miR-144-3p levels in 110 human ccRCC tissues, and found that miR-144-3p levels in ccRCC tissues were increased compared with adjacent normal tissues. Pearson correlation analysis revealed that miR-144-3p levels in tumor tissues were positively correlated with preoperative plasma miR-144-3p levels in the matched samples from patients with ccRCC. In addition, the miR-144-3p levels in ccRCC plasmas and tissues were increased in patients with advanced pT stage.

Conclusions: Our data indicate that miR-144-3p, which is significantly up-regulated in ccRCC plasmas and tissues, particularly with advanced pT stage, is a novel and excellent plasma biomarker for the diagnosis of ccRCC.

Keywords: Biomarker; Clear cell renal cell carcinoma; Plasma; miR-144-3p.

MeSH terms

  • Angiomyolipoma / blood
  • Angiomyolipoma / diagnosis*
  • Area Under Curve
  • Biomarkers, Tumor / blood
  • Carcinoma, Renal Cell / diagnosis*
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / surgery
  • Female
  • Humans
  • Kidney / metabolism
  • Kidney Neoplasms / diagnosis*
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / surgery
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Nephrectomy
  • Oligonucleotide Array Sequence Analysis
  • ROC Curve
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • MIRN144 microRNA, human
  • MicroRNAs