Literature DB >> 27499952

Mutations and expression of the NFE2L2/KEAP1/CUL3 pathway in Chinese patients with lung squamous cell carcinoma.

Yongxing Zhang1, Hong Fan1, Shuo Fang1, Lin Wang1, Li Chen1, Yulin Jin1, Wei Jiang1, Zongwu Lin1, Yu Shi1, Cheng Zhan1, Qun Wang1.   

Abstract

BACKGROUND: Recent studies have reported an abnormally high alteration rate in the nuclear factor erythroid 2-like 2 (NFE2L2)/kelch-like ECH-associated protein 1 (KEAP1)/cullin 3 (CUL3) pathway. But the status of this pathway in Chinese patients with lung squamous cell carcinoma (SqCC) has not been thoroughly studied, and there are many uncertainties regarding the expression of pathway intermediates.
METHODS: cDNA sequencing and TaqMan qRT-PCR were carried out in paired cancer and adjacent normal samples obtained from 100 Chinese patients with lung SqCC. Immunohistochemical staining was performed in 50 other paraffin-embedded specimens.
RESULTS: We detected 47 mutations in 36 patients (36%), and 143 single nucleotide polymorphism (SNP) in 59 patients (59%), of which 41 mutations and 31 SNPs resulted in amino acid (AA) and possibly functional changes. By combining qRT-PCR and immunohistochemistry staining, we confirmed that the expression of NFE2L2 and KEAP1 were highly increased, while the expression of CUL3 was not significantly changed in lung SqCC samples from Chinese patients.
CONCLUSIONS: Considering the frequent mutations and abnormal expression, the NFE2L2/KEAP1/CUL3 pathway may play an important role in the therapy of Chinese patients with lung SqCC.

Entities:  

Keywords:  Nuclear factor erythroid 2-like 2 (NFE2L2); cullin 3 (CUL3); kelch-like ECH-associated protein 1 (KEAP1); lung SqCC; mutation

Year:  2016        PMID: 27499952      PMCID: PMC4958875          DOI: 10.21037/jtd.2016.06.08

Source DB:  PubMed          Journal:  J Thorac Dis        ISSN: 2072-1439            Impact factor:   2.895


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