RESUMEN
The present study assessed whether estrogen receptor (ER)ß1 is associated with the survival of patients with advanced lung adenocarcinoma, with or without mutations of the epidermal growth factor receptor (EGFR) following treatment with EGFR-tyrosine kinase inhibitors (TKIs). Pathologically confirmed stage IV lung adenocarcinomas were assessed for EGFR mutations and ERß1 expression. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and the log-rank test. A total of 122 out of the 201 (60.7%) patients had EGFR mutations, 64 (31.8%) of which were EGFR Del19 and 58 mutations (28.9%) were EGFR exon 21 L858R mutation. The presence of EGFR mutations was significantly increased in female patients compared with male patients (P<0.001) and in non-smokers compared with smokers (P<0.001). Patients with EGFR mutations had a significantly improved PFS and OS compared with patients without EGFR mutations treated with EGFR-TKIs. Furthermore, ERß1 expression was significantly increased in patients with EGFR mutations compared with patients without EGFR mutations (P=0.001). However, the median PFS (P=0.005) and OS (P=0.002) of patients carrying the EGFR exon 21 L858R mutation was significantly decreased in patients with tumors where ERß1 cytoplasmic expression was high. The multivariate analysis demonstrated that ERß1 expression was the only independent predictor of PFS (P=0.002) and OS (P=0.003) in patients carrying the EGFR exon 21 L858R mutation. The data demonstrated that ERß1 expression may predict outcomes of patients with lung adenocarcinoma treated with EGFR-TKI.
RESUMEN
OBJECTIVE: This study examined microRNA-92 (miR-92) expression level in relation to the mRNA level of its potential target gene, estrogen receptor ß1 (ERß1), in female patients diagnosed with pelvic organ prolapse (POP). STUDY DESIGN: Between July 2012 and September 2014, a total of 104 patients were recruited at the First Affiliated Hospital of Sun Yat-sen University, which included 56 POP patients and 48 non-POP control subjects. Based on POP-Q score, the POP patients were further categorized into POP II and POP III groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify miR-92 expression level. ERß1 tissue expression was measured by western blot and immunohistochemistry (IHC) methods. SPSS 19.0 software was used for statistical analysis. RESULTS: No remarkable differences were observed between the POP group and non-POP group, and between the POP II and POP III groups, with respect to age, body mass index (BMI), parity, menopause status, and family history of POP. The expression level of miR-92 in the POP group was dramatically higher than the non-POP group (P<0.05). Consistent with the disease status, miR-92 expression level in POP III group was markedly higher than the POP II group (P<0.05). Western blot analysis revealed significantly reduced levels of ERß1 in the POP group compared to the non-POP group, with similar results obtained between the POP III and POP II groups (all P<0.05). IHC results showed ERß1 staining mainly in the nucleus and semi-quantitative measurements, expressed as positive expression rate, revealed that ERß1 level in the POP group was clearly lower than non-POP group. Finally, statistical analysis of IHC results from uterosacral ligament tissue showed inverse correlation between miR-92 and ERß1 expression levels in POP patients (P<0.05). CONCLUSIONS: Our results revealed increased miR-92 expression and decreased ERß1 level in uterosacral ligaments of women diagnosed with POP, compared to non-POP subjects POP III patients exhibited more severe changes than POP II patients. Further, ERß1expression is inversely correlated to miR-92 expression. Taken together, our results suggest that miR-92 and ERß1 expression levels may be used as reliable diagnostic markers for assessing the severity of POP.