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Clinical Implications of the Autophagy Core Gene Variations in Advanced Lung Adenocarcinoma Treated with Gefitinib

Jupeng Yuan1, Nasha Zhang1,2, Longbin Yin3

  • 1Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.

Scientific Reports
|December 21, 2017
PubMed

Insights

Genetic variants in autophagy core genes impact advanced lung adenocarcinoma patient outcomes with gefitinib treatment. Specific ATG gene polymorphisms are linked to survival and gefitinib resistance, suggesting personalized treatment strategies.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) offer significant benefits for advanced lung adenocarcinoma with EGFR mutations.
  • Autophagy plays a crucial role in the efficacy of EGFR-TKIs treatments.

Purpose of the Study:

  • To investigate the association between genetic variants in autophagy core genes and the treatment outcomes of advanced lung adenocarcinoma patients receiving gefitinib.
  • To identify specific polymorphisms that predict survival and gefitinib resistance.

Main Methods:

  • Systematic examination of 27 potentially functional genetic polymorphisms in 11 autophagy core genes.
  • Analysis of 108 patients with advanced lung adenocarcinoma treated with gefitinib.
  • Association analysis with patient survival, disease prognosis, and gefitinib resistance.

Main Results:

  • Several autophagy gene polymorphisms (ATG10 rs10036653, ATG12 rs26538, ATG16L1 rs2241880, ATG16L2 rs11235604) were significantly associated with overall survival.
  • Specific variants in ATG5, ATG7, ATG10, ATG12, ATG16L1, and ATG16L2 were linked to prognosis in EGFR-mutant patients.
  • ATG5 and ATG10 polymorphisms were associated with primary or acquired resistance to gefitinib.
  • Functional analysis suggested ATG10 rs10036653 polymorphism may influence OCT4 transcription factor binding.

Conclusions:

  • Autophagy core gene variants have potential clinical implications for gefitinib treatment in advanced lung adenocarcinoma.
  • Germline and somatic variation detection may enable patient-tailored EGFR-TKI treatment decisions.
  • These findings highlight the importance of genetic background in predicting treatment response.

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