Research Paper Volume 12, Issue 10 pp 9292—9310

PIWI-interacting RNAs piR-13643 and piR-21238 are promising diagnostic biomarkers of papillary thyroid carcinoma

Zhengyan Chang1, *, , Guo Ji1, *, , Runzhi Huang2,3, *, , Hong Chen4, , Yaohui Gao1, , Weifeng Wang5, , Xuechen Sun1, , Jie Zhang3,6, , Jiayi Zheng1,7, , Qing Wei1, ,

  • 1 Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai
  • 2 Division of Spine, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, China
  • 3 Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University), Ministry of Education, Shanghai, China
  • 4 Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
  • 5 Central Laboratory, Shanghai Tenth People's Hospital, Shanghai, China
  • 6 Department of Prevention, Tongji University School of Medicine, Tongji University, Shanghai, China
  • 7 Human Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, China
* Co-first authors and Equal contribution

Received: December 17, 2019       Accepted: April 17, 2020       Published: May 19, 2020
How to Cite

Copyright © 2020 Chang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Emerging studies demonstrate that PIWI-interacting RNAs (piRNAs) participate in the development of cancers. 75 pairs of papillary thyroid carcinoma (PTC) samples and 31 benign thyroid nodule samples were included in this three-phase biomarker identifying study. First, piRNA expression profiles of five pairs of PTC samples were acquired piRNA sequencing. The expression of all upregulated piRNAs were further validated by RT-qPCR. Paired t and nonparametric test were used to evaluate the association between all upregulated piRNAs and clinic stage. The expression levels of key piRNAs were corrected by demographic data to construct a multivariate model to distinguish malignant nodules from benign. Additionally, the intersection between target genes of key piRNAs and differentially expressed genes in The Cancer Genome Atlas (TCGA) PTC samples were used to perform enrichment analysis. Only piR-13643 and piR-21238 were significantly upregulated in PTC and associated with clinic stage. Moreover, both piR-13643 (Area Under Curve (AUC): 0.821) and piR-21238 (AUC: 0.823) showed better performance in distinguishing malignant nodules from benign than currently used biomarkers HBME1 (AUC: 0.590). Based on our findings, piR-13643 and piR-21238 were observed to be significantly upregulated in human PTC. PIWI-interacting RNAs could serve as promising novel biomarkers for accurate detection of PTC.


miRNAs: microRNAs; piRNAs: PIWI-interacting RNAs; NGS: next generation sequencing; RT-qPCR: Reverse Transcription Quantitative Polymerase Chain Reaction; UICC: Union for International Cancer Control; AJCC: American Joint Committee on Cancer; DEGs: differentially expressed genes; TCGA: The Cancer Genome Atlas; FC: Fold Change; FDR: False Discovery Rate; TPM: Transcripts per million; ROC: receiver operating characteristic curves; AUC: Area Under Curve; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes.