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Identification of NMU as a potential gene conferring alectinib resistance in non-small cell lung cancer based on

Shuangjie You1, Lei Gao1

  • 1Department of Heart Failure, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.

Gene
|August 11, 2018
PubMed

Insights

Neuromedin U (NMU) may cause resistance to alectinib, a targeted therapy for non-small cell lung cancer (NSCLC). This discovery, based on bioinformatics, offers insights into overcoming treatment challenges in NSCLC patients with ALK-rearrangements.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Non-small cell lung cancer (NSCLC) is a prevalent malignancy.
  • Targeted therapies like alectinib offer benefits for NSCLC patients with specific genomic alterations, such as anaplastic lymphoma kinase (ALK) rearrangements.
  • Therapeutic resistance to alectinib is a significant clinical challenge, limiting treatment efficacy.

Purpose of the Study:

  • To identify potential mechanisms contributing to alectinib resistance in NSCLC.
  • To investigate the role of neuromedin U (NMU) in conferring resistance to alectinib treatment.
  • To explore NMU as a therapeutic target for overcoming alectinib resistance.

Main Methods:

  • Integrative bioinformatics analysis of three microarray datasets.
  • Identification of NMU as a candidate gene overexpressed in NSCLC and alectinib-resistant cells.
  • Validation through protein/gene interaction analysis, biological process annotation, and transcription factor analysis.

Main Results:

  • Neuromedin U (NMU) was identified as significantly overexpressed in both NSCLC tissues and alectinib-resistant NSCLC cell lines.
  • Bioinformatics analyses supported NMU's role in conferring alectinib resistance through multiple mechanisms.
  • Further analysis confirmed the involvement of transcription factors regulating NMU mRNA expression.

Conclusions:

  • Neuromedin U (NMU) is implicated as a key factor in the development of alectinib resistance in non-small cell lung cancer.
  • Targeting NMU may represent a novel therapeutic strategy to overcome alectinib resistance in NSCLC patients with ALK-rearrangements.
  • These findings provide a basis for further experimental validation and clinical investigation.
Keywords:
Alectinib resistanceBioinformatics analysisLung cancerNeuromedin U

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