Circulating Long Non-Coding RNAs Act as Biomarkers for Predicting 131I Uptake and Mortality in Papillary Thyroid Cancer Patients with Lung Metastases

Cell Physiol Biochem. 2016;40(6):1377-1390. doi: 10.1159/000453190. Epub 2016 Dec 19.

Abstract

Purpose: The aims of the current study were to explore plasma lncRNAs as a novel biomarker panel for the diagnosis of non-131I-avid lung metastases of PTC and to investigate the plasma lncRNA expression levels associated with survival in PTC patients with lung metastases.

Methods: The expression of lncRNAs was examined using an lncRNA microarray chip. The lncRNAs with the most significant difference in expression between PTC patients with non-131I-avid lung metastases and PTC patients with 131I-avid lung metastases were verified by quantitative reverse-transcription polymerase chain reaction. The Kaplan-Meier method was used to determine whether the plasma lncRNA levels might be indicative of patient prognosis.

Results: Compared with 131I-avid lung metastases, we discovered that two lncRNAs (ENST00000462717 andENST00000415582) were upregulated and two (TCONS_00024700 and NR_028494) were downregulated in the non-131I-avid lung metastases of PTC. Receiver operating characteristic curve (ROC) analyses indicated that the use of these four lncRNAs had high diagnostic sensitivity and specificity for predicting non-131I-avid lung metastases of PTC. The merged areas under the curve for ENST00000462717, ENST00000415582, TCONS_00024700,and NR_028494 in the training and validation sets were 0.890, 0.936, 0.975, and 0.918, respectively. Low (ENST00000462717 and ENST00000415582) and high plasma lncRNA levels(TCONS_00024700and NR_028494) were also found to be associated with better prognosis of PTC patients with lung metastases(P<0.001).

Conclusions: ENST00000462717, ENST00000415582, TCONS_00024700, and NR_028494 may be used as novel and minimally invasive markers for the diagnosis and prognostic assessment of non-131I-avid lung metastases from PTC.

MeSH terms

  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Carcinoma / blood
  • Carcinoma / diagnostic imaging*
  • Carcinoma / mortality*
  • Carcinoma, Papillary
  • Case-Control Studies
  • Demography
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Iodine Radioisotopes / metabolism*
  • Kaplan-Meier Estimate
  • Lung Neoplasms / secondary*
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • RNA, Long Noncoding / blood*
  • RNA, Long Noncoding / genetics
  • ROC Curve
  • Reproducibility of Results
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / blood
  • Thyroid Neoplasms / diagnostic imaging*
  • Thyroid Neoplasms / mortality*

Substances

  • Biomarkers, Tumor
  • Iodine Radioisotopes
  • RNA, Long Noncoding