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Transcriptome Sequencing Reveals Key Pathways and Genes Associated with Cisplatin Resistance in Lung Adenocarcinoma

Yani Fang1, Cheng Zhang1, Tong Wu1

  • 1National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University, Xi'an, PR China.

Plos One
|January 24, 2017
PubMed

Insights

Acquired cisplatin resistance in lung adenocarcinoma involves distinct gene expression changes. Key pathways like PI3K/AKT and cell adhesion are implicated, offering potential biomarkers and therapeutic targets for non-small cell lung cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Acquired resistance to cisplatin chemotherapy is a significant challenge in treating non-small cell lung cancer (NSCLC).
  • The molecular mechanisms driving cisplatin resistance in lung adenocarcinoma remain incompletely understood.
  • Identifying specific gene expression patterns associated with resistance is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate distinct gene expression patterns linked to acquired cisplatin resistance in human lung adenocarcinoma.
  • To identify potential molecular biomarkers and therapeutic targets for cisplatin-resistant lung cancer.

Main Methods:

  • Whole-transcriptome sequencing was employed to compare gene expression profiles.
  • A cisplatin-resistant human lung adenocarcinoma cell line (A549/DDP) was compared with its sensitive progenitor cell line (A549).
  • Differentially expressed genes (DEGs) were identified and functionally annotated using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.

Main Results:

  • A total of 1214 DEGs were identified between the resistant and sensitive cell lines.
  • 656 genes were upregulated, and 558 genes were downregulated in the cisplatin-resistant cells.
  • Enriched pathways in resistant cells included PI3K/AKT, mitogen-activated protein kinase (MAPK), actin cytoskeleton regulation, and focal adhesion.

Conclusions:

  • Gene expression patterns, particularly involving cell adhesion and cytoskeleton regulation, are associated with cisplatin resistance in lung adenocarcinoma.
  • The PI3K/AKT and MAPK signaling pathways play a role in conferring chemotherapy resistance.
  • These findings suggest novel biomarkers for NSCLC prognosis and potential therapeutic targets for overcoming cisplatin resistance.

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