HER4 isoform CYT2 and its ligand NRG1III are expressed at high levels in human colorectal cancer

Guo,Yan; Duan,Zhihui; Jia,Yitao; Ren,Chaoying; Lv,Jian; Guo,Peng; Zhao,Wujie; Wang,Bin; Zhang,Suqiao; Li,Yaxing; Li,Zhongxin

doi:10.3892/ol.2018.8124

HER4 isoform CYT2 and its ligand NRG1III are expressed at high levels in human colorectal cancer

Authors:
- Yan Guo
- Zhihui Duan
- Yitao Jia
- Chaoying Ren
- Jian Lv
- Peng Guo
- Wujie Zhao
- Bin Wang
- Suqiao Zhang
- Yaxing Li
- Zhongxin Li
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Affiliations: Second Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050035, P.R. China, Third Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China, Department of Orthopedics, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050035, P.R. China
Published online on: February 27, 2018 https://doi.org/10.3892/ol.2018.8124
Pages: 6629-6635

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Abstract

The present study aimed to evaluate the expression of human epidermal growth factor receptor (HER4) isoforms and their ligand neuregulin 1 (NRG1) isoforms in human primary colorectal cancer (CRC). The mRNA expression of HER4 isoforms JM‑a, JM‑b, CYT1 and CYT2, and their ligand isoforms NRG1 I, II and III in CRC tissues and adjacent normal tissues were quantified by reverse transcription‑quantitative polymerase chain reaction analysis. Univariate analysis and logistic regression analysis were performed to analyze the association between HER4 and NRG1 expression and lymph node metastasis in CRC. The expression levels of CYT1 (P=0.002), CYT2 (P=0.002) and NRG1 type III (P<0.001) were significantly higher in the CRC tissues than in the adjacent normal tissues. The expression of CYT2 was correlated with tumor stage (P=0.018), lymph node status (P=0.015) and tumor‑node‑metastasis (P=0.038) in CRC. The expression of NRG1III was correlated with lymph node metastasis, and the expression of CYT2 was associated with the expression of NRG1III (r=0.691, P<0.01). The logistic regression analysis indicated that expression of CYT2 >50 was a risk factor for lymph node metastasis in CRC. In conclusion the expression levels of CYT1, CYT2 and NRG1III were upregulated in CRC. An expression of CYT‑2 >50 was identified as a risk factor for lymph node metastasis in CRC. Therefore, CY‑2 and NRG1III may be involved in the progression of CRC.

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