Predictive value of microRNA let-7a expression for efficacy and prognosis of radiotherapy in patients with lung cancer brain metastasis: A case-control study.

BACKGROUND: As a well-known cancer with high mortality, lung cancer has been implied to be closely associated with brain metastasis. Despite notable advances, effective treatment methods are still in urgent need. This study aims to investigate the value of serum microRNA-let-7a (miR-let-7a) expression in predicting efficacy and prognosis of radiotherapy in patients with lung cancer brain metastasis. METHODS: To begin with, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed for better understand of the correlation between miR-let-7a and lung cancer. Afterwards, the relationship between serum miR-let-7a expression and radiotherapy efficacy was analyzed by receiver operating characteristic curve analysis. Following successful transfection, RT-qPCR and Western blot assay were utilized for evaluating the involvement of miR-let-7a in regulation of DICER1 expression in lung cancer cell line. Then, whether miR-let-7a was implicated in proliferation and cell cycle distribution of lung cancer cells were confirmed by cell counting kit-8 assay and flow cytometry respectively. RESULTS: Initially, it was revealed that serum miR-let-7a expression was decreased in lung cancer. Later, we found that decreased miR-let-7a displayed an unfavorable role in radiotherapy efficacy and overall survival rate of patients with lung cancer brain metastasis. After the successful transfection, the inverse relationship between miR-let-7a and DICER1 expression was uncovered. Meanwhile, biological behaviors of lung cancer cells were presented to be limited after transfection of overexpressed miR-let-7a. CONCLUSION: Our findings demonstrated that the lower expression of miR-let-7a in patients with lung cancer brain metastasis was closely related to unfavorable efficacy and prognosis of radiotherapy, and it may be an important predictive biomarker by regulation of DICER1.

Significance of interstitial tumor-associated macrophages in the progression of lung adenocarcinoma.

Stepwise progression from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) to lepidic predominant adenocarcinoma (LPA) was proposed by various scholars. Interstitial tumor-associated macrophages (TAMs) and various potential chemokines involved in the progression from AIS/MIA to LPA were hypothesized. In the present study, immunohistochemistry or immunofluorescent double staining was used to detect the expression of the TAMs marker cluster of differentiation (CD) 68, tumor-derived colony-stimulating factor (CSF)-1, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, E-cadherin and Snail in lung adenocarcinoma specimens, including AIS/MIA, LPA and other types. It was observed that infiltrating TAMs were negatively associated with the prognosis of patients, and that the infiltration degree of interstitial TAMs was higher in LPA than that in AIS/MIA. In addition, E-cadherin, Snail and MMP-2 expression were significantly correlated with the infiltration degree of TAMs. Survival analysis revealed that co-expression of CD68, CSF-1 and IL-6 was an independent prognostic factor. Stratified analysis demonstrated that, in AIS/MIA patients, there was a statistically significant difference between the number of TAMs (TAMs ≤25 and TAMs >25) in the CD68+CSF-1+IL-6+ group compared with other groups (including CD68+CSF-1-IL-6-, CD68+CSF-1+IL-6-, CD68+CSF-1-IL-6+ and CD68- groups). By contrast, in patients with TAMs >25 and in patients with positive CD68, CSF-1 and IL-6 expression, the survival rates were not significantly different between AIS/MIA and LPA. These results suggested that co-expression of TAMs marker CD68, CSF-1 and IL-6 may be a valuable independent prognostic predictor in lung adenocarcinoma. TAMs may facilitate AIS/MIA progression to LPA, which may be closely associated with the induction of the epithelial-mesenchymal transition.