Correlation between expression of long non-coding RNA ZXF1 and prognosis of lung adenocarcinoma and its potential molecular mechanism / 中华肿瘤杂志

ABSTRACT

Objective@#To investigate the correlation between expression of long non-coding RNA (lncRNA) ZXF1 and clinicopathological characteristics, as well as prognosis of lung adenocarcinoma; and to explore its potential molecular mechanism.@*Methods@#A total of 83 lung adenocarcinoma tissue samples and 83 paracancerous lung tissue samples from lung adenocarcinoma patients were collected. The mRNA expression of ZXF1 in the tumors and the corresponding adjacent non-tumor tissues were determined by real-time fluorescence quantitative PCR. The correlation between ZXF1 level and clinicopathological characteristics such as age, gender, smoking history, tumor size, tumor differentiation and lymph node metastasis was evaluated. Survival analysis was performed using Kaplan-Meier and Cox multivariate regression, based on the data of a 12-56 months follow-up after surgery. In vitro ZXF1 was over-expressed in lung adenocarcinoma A549 cells, and then the proteins functionally related to ZXF1 were identified by protein array analysis.@*Results@#Of the 83 cases of lung adenocarcinoma, the ZXF1 mRNA levels in the tumor and adjacent non-tumor tissues were 8.32±3.05 and 1.05±0.47, respectively (P<0.05), and a high-level the high expression of ZXF1 in the tumor tissues was detected in 56 cases. The expression status of ZXF1 was closely correlated with the tumor differentiation and lymph node metastasis (P<0.05), but was not significantly related to age, gender and tumor size. Based on a 12-56 months follow-up, the patients with high level ZXF1 expression had a shorter disease free survival (DFS) and overall survival (OS) than that of the group with low level ZXF1 (all P<0.05). Multivariate analysis showed that ZXF1 expression, tumor size and lymph node metastasis were independent risk factors to DFS; and ZXF1 expression, tumor size, lymph node metastasis and tumor differentiation were independent risk factors to OS. The protein array data revealed that expressions of bone morphogenetic protein 5 (BMP-5)and stem cell factor receptor (SCFR)were upregulated upon overexpression of the ZXF1 in A549 cells.@*Conclusions@#lncRNA ZXF1 is overexpressed in lung adenocarcinoma, and is closely correlated with tumor differentiation and lymph node metastasis. As an independent risk factor, a high expression of ZXF1 indicates a poor prognosis for the patients. ZXF1 may influence the biological behavior of lung adenocarcinoma by enhancing the protein expression of BMP-5 and SCFR.