mRNA expression of programmed cell death ligand 1 and components of the phosphatidylinositol 3-kinase/AKT/phosphatase and tensin homolog pathway in epidermal growth factor receptor mutation-positive lung adenocarcinoma.

Abstract

OBJECTIVE:

The objective of this study is to investigate the relationship between programmed cell death ligand 1 (PD-L1) expression and the mutation status of epidermal growth factor receptor (EGFR) in lung adenocarcinoma, as well as the correlation between the clinical features of patients and mRNA levels of PD-L1 and components of the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT)/phosphatase and tensin homolog (PTEN) pathways.

METHODS:

mRNA levels of PD-L1, PI3K, AKT, and PTEN in tumor and matched normal tissues of patients with EGFR mutation-positive lung adenocarcinoma were determined by real-time polymerase chain reaction.

RESULTS:

Twenty-three patients with EGFR mutation-positive lung adenocarcinoma were enrolled, and 46 samples (23 pairs of tumor and matched normal lung tissues) were collected. PD-L1 and AKT mRNA levels were higher in EGFR mutation-positive lung adenocarcinoma than in matched normal lung tissues (P = 0.047 and P = 0.046, respectively), whereas PI3K and PTEN mRNA levels were significantly lower in the cancerous tissues (P = 0.009 and P = 0.039, respectively). PD-L1 expression was positively correlated with PI3K/AKT signaling pathway activation. PD-L1 upregulation in lung adenocarcinoma was positively correlated with EGFR exon 19 mutations (P = 0.034). AKT mRNA upregulation was correlated with lymph node metastasis (P = 0.034). PTEN mRNA downregulation was correlated with high tumor staging and lymph node metastasis (P = 0.035 and P = 0.014, respectively).

CONCLUSION:

Elevated PD-L1 mRNA expression in lung adenocarcinoma is associated with EGFR mutation and may be mediated through the PI3K-AKT pathway. EGFR exon 19 mutations closely correlate with increased PD-L1 mRNA expression. Increased AKT mRNA expression correlates with lymph node metastasis, while decreased PTEN mRNA levels correlate with advanced tumor stage and lymph node metastasis.

• Authors: Ke Han, Yi Zhang
• Journal: Journal of cancer research and therapeutics (J Cancer Res Ther) Vol. 15 Issue 4 Pg. 914-920 ( 2019) ISSN: 1998-4138 [Electronic] India
• PMID: 31436252 (Publication Type: Journal Article)

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human
• RNA, Messenger
• Phosphatidylinositol 3-Kinase
• EGFR protein, human
• ErbB Receptors
• AKT1 protein, human
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase
• PTEN protein, human

Topics

• Adenocarcinoma of Lung (genetics, pathology)
• B7-H1 Antigen (genetics, metabolism)
• Biomarkers, Tumor (genetics, metabolism)
• Case-Control Studies
• ErbB Receptors (genetics, metabolism)
• Female
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (genetics, secondary)
• Lymphatic Metastasis
• Male
• Middle Aged
• Mutation
• Neoplasm Invasiveness
• PTEN Phosphohydrolase (genetics, metabolism)
• Phosphatidylinositol 3-Kinase (genetics, metabolism)
• Prognosis
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)