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Elevated integrin α6 expression is involved in the occurrence and development of lung adenocarcinoma, and predicts a poor prognosis: a study based on immunohistochemical analysis and bioinformatics

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Objective

To study integrin α6 expression in lung adenocarcinoma tissue through comparison with matching adjacent non-cancerous tissues as well as elucidating the correlation between integrin α6 expression with the clinical parameters of lung adenocarcinoma. We also explore the signal pathways associated with integrin α6 up-regulation.

Methods

The clinical data, cancer tissues, and adjacent non-cancerous tissues of 30 patients diagnosed with lung adenocarcinoma were collected from Taizhou Hospital in Zhejiang Province, China, in 2010. The protein levels of integrin α6 were determined by immunohistochemistry methods. mRNA data of 85 lung adenocarcinoma tissues and 14 normal tissues as well as clinical results were collected from GEO30219. We also collected mRNA data of 533 lung adenocarcinoma tissues and 59 normal tissues as well as the clinical results of 522 patients with lung adenocarcinoma from the Cancer Genome Atlas (TCGA) database. The differences in protein and mRNA levels in cancer tissues and non-cancerous tissues were analyzed, and we subsequently investigated the association between integrin α6 expression and key parameters indicating lung adenocarcinoma progression and overall survival rate. Additionally, the possible pathways involved in the up-regulation of integrin α6 were analyzed by GSEA.

Results

The protein levels of integrin α6 in lung adenocarcinoma tissues were significantly higher than those in adjacent tissues (p < 0.01), and were positively correlated with the grade and T stage of lung adenocarcinoma (p < 0.05). Patients with low integrin α6 protein levels had higher survival rates (p < 0.05). The analysis of gene chip data from the TCGA database also showed that the integrin α6 mRNA level was significantly correlated with T stage (p < 0.05), overall survival (OS) rate (p < 0.01), and disease-free survival (DFS) rate (p = 0.005). GSEA gene enrichment analysis identified a series of pathways that may be associated with integrin α6 up-regulation, including the AGR, PYK2, ECM, and PTEN pathways.

Conclusion

Integrin α6 plays an important role in the occurrence and progression of lung adenocarcinoma and may act as a prognostic predictor of lung adenocarcinoma in patients. Based on the results of the present study, integrin α6 may be a potential target gene for the treatment of lung adenocarcinoma.

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Funding

This study was funded by Zhejiang Provincial Natural Fund (The Mechanism of Integrin Mediated Wnt/β-catenin Signaling Pathway in Regulating Lymphangiogenesis in Lung Cancer) (grant number LQ18H160029).

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Author notes

  1. Jianfei Shen and Jianfeng Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province, Zhejiang University, Taizhou, 317000, China

    Jianfei Shen & Chengchu Zhu

  2. Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou, 317000, China

    Jianfei Shen, Jianfeng Xu, Baofu Chen, Dehua Ma, Zixuan Chen & Chengchu Zhu

  3. Institute of Cell Biology, Zhejiang University, Hangzhou, 310058, China

    Jianfei Shen & Ji-Cheng Li

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  1. Jianfei Shen
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  2. Jianfeng Xu
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  4. Dehua Ma
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Correspondence to Ji-Cheng Li or Chengchu Zhu.

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The study has been approved by the ethics committee and patients gave their informed consent before material was obtained for use in the study.

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Shen, J., Xu, J., Chen, B. et al. Elevated integrin α6 expression is involved in the occurrence and development of lung adenocarcinoma, and predicts a poor prognosis: a study based on immunohistochemical analysis and bioinformatics. J Cancer Res Clin Oncol 145, 1681–1693 (2019). https://doi.org/10.1007/s00432-019-02907-1

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  • DOI: https://doi.org/10.1007/s00432-019-02907-1

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