Journal of Diagnostics Concepts & Practice ›› 2019, Vol. 18 ›› Issue (04): 402-411.doi: 10.16150/j.1671-2870.2019.04.005

• Original articles • Previous Articles     Next Articles

Screening and identification of clinical molecular targets in papillary thyroid cancers

YANG Chihui1,2, ZHANG Jing1, MENG Leijun3, GONG Liping4, CHANG Qing5, ZHANG Hong3(), ZENG Naiyan1()   

  1. 1. Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine,Shanghai 200025, China
    2. Department of Clinical Laboratory, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
    3. Department of Clinical Laboratory, Children’s Hospital of Shanghai Jiao Tong University, Shanghai 200040, China
    4. Capital Medical University of Basic Medicine, Beijing 100054, China
    5. Central Laboratory, Shanghai Jiading District Central Hospital, Shanghai University of Medicine & Health Sciences, Shanghai 201800, China
  • Received:2018-10-22 Online:2019-08-25 Published:2019-08-25
  • Contact: ZHANG Hong,ZENG Naiyan E-mail:zhanghong3010@126.com;zengny@shsmu.edu.cn

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Abstract:

Objective: To identify the clinical molecular targets in papillary thyroid cancer (PTC) by analyzing the diffe-rential expression of the NF-κB signal pathway related genes and mutations of 52 solid tumor-related genes in PTC against normal adjacent tissue (NAT). Methods: RNA and DNA of tumor and NAT were extracted from formalin-fixed paraffin-embedded (FFPE) tissue of 20 papillary thyroid cases. The mRNA and protein expressions of NF-κB signal pathway related gene CD44, BCL2, CCND2, c-FLIP, IκBα, A20 and ABINs were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively. Mutations in 5 relapse cases were detected by targeted next-generation sequencing (NGS). Results: Expressions of CD44 and CCND2 were significantly higher at both RNA and protein level in PTC tumor tissue than those in NAT. The expressions of NF-κB signal pathway related genes were not significantly different between PTC having and not having lymph node metastasis. Results of NGS showed that ALK, BRAF, FGFR3/4, KIT, MYC and MAPK signal pathway genes HRAS, KRAS, NRAS, RET were mutated in PTC cases with a high frequency. Two cases had 35 and 40 mutation genes, respectively, and having high tumor burden; clinical data showed that these two were relapse cases after operation. BRAF V600E mutation was not always a tumor specific mutation (64%), but also could be a germline mutation (29%). Real-time quantitative PCR (qPCR) and NGS had a high consistent rate (80%) for the detection of V600E mutation. Conclusions: The high expressions of CD44 and CCND2 in PTC tumor tissue and the tumor specific mutations in BRAF, RAS, FGFRs, KIT and MYC genes might be used as clinical molecular markers for selection of targeted therapy of individual PTC patient. NGS and qPCR had high consistence for detection of BRAF V600E, and used jointly could improve the detection rate.

Key words: Papillary thyroid cancer, Real-time quantitative PCR (qPCR), Targeted sequencing, NF-κB target genes, BRAF V600E mutation

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