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  • Title: Lung adenocarcinoma resistance to therapy with EGFR‑tyrosine kinase inhibitors is related to increased expression of cancer stem cell markers SOX2, OCT4 and NANOG.
    Author: Hu F, Li C, Zheng X, Zhang H, Shen Y, Zhou L, Yang X, Han B, Zhang X.
    Journal: Oncol Rep; 2020 Feb; 43(2):727-735. PubMed ID: 31894290.
    Abstract:
    The present study aimed to explore the relationship between the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKIs) and the expression of the cancer stem cell (CSC)‑related markers. Specimens of 72 cases of lung adenocarcinoma with significantly different therapeutic effects of the first‑generation EGFR‑TKI treatment were collected. The patients were divided into a sensitive group [progression‑free survival (PFS) longer than 26 months] and a resistant group (PFS less than 5 months) according to the efficacy of first‑line EGFR‑TKI treatment. The expression of CSC‑related markers (OCT4, SOX2, NANOG) in tumor tissues of the two groups was detected by immunohistochemical (IHC) staining, immunofluorescence and reverse transcriptase‑quantitative polymerase chain reaction (RT‑qPCR). IHC staining was quantified using H‑scores. The unpaired nonparametric t‑test was used to detect the differences in the results of IHC and RT‑qPCR analyses between the groups. The Chi‑square test was used to detect the differences in the clinical characteristics between the two groups. The t‑test revealed that the IHC H‑scores of SOX2 (P=0.003), OCT4 (P=0.036) and NANOG (P=0.032) were significantly higher in the resistant group than in the sensitive group. The results of RT‑qPCR revealed that the relative levels of SOX2 (P=0.018), OCT4 (P=0.035) and NANOG (P=0.044) were significantly higher in the resistant group than in the sensitive group. The number of male patients, patients who smoked, patients with stage IV lung adenocarcinoma disease, and patients with poor differentiation was higher in the resistant group than in the sensitive group, with statistically significant differences. The poor efficacy of first‑generation EGFR‑TKIs for lung adenocarcinoma appears to be related to the increased expression of CSC markers.
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