Abstract 23P
Background
Metastasis is a critical factor for the high mortality in Non-small-cell lung carcinoma (NSCLC), but the mechanism is still not completely understood. DAB2IP, as a Ras GTPase-activating protein and novel scaffold protein, is involved in the progression of various cancers. Previously, it was reported that DAB2IP methylation status in circulating DNA could predict response to erlotinib in EGFR-mutated NSCLC patients. However, the role of DAB2IP in NSCLC has rarely been investigated.
Methods
We collected 148 paraffin embedding tissues from primary NSCLC without distant metastases, and analyzed the relationship between DAB2IP and clinical pathology. We also used a lentivirus system to build the stable DAB2IP knockdown cell line A549-KD and compared the metastatic ability in vitro with A549 cells transfected with control shRNA (shcon). Cell-cell and cell-matrix adhesion was also investigated in vitro. The clinical tissue analysis was approved by the Medical Ethics Committee in the First Affiliated Hospital of Chongqing Medical University.
Results
In 148 patients, regional metastases were found in 96 patients. In 96 patients with metastases, no or low-expression of DAB2IP was observed in a high number of patients (79 no or low/96 patients; 17 high/96 patients), while high expression was frequently detected in patients without metastasis (8 no or low/52 patients; 44 high/52 patients). This suggests that loss of DAB2IP could indicate the occurrence of metastases in lung cancer patients(p<0.0001). The patients with high expression of DAB2IP also had longer disease-free survival after surgery (p=0.013). In vitro, A549-KD cells migrated faster in wound healing assays. Further, knocking down DAB2IP expression reduced the adhesion of A549 on Laminin 111 and fibronectin, which destroyed cell-matrix adhesion. Meanwhile, the expression of some cell-cell adhesion proteins (E-cadherin, Epcam and MelCAM) also decreased in A549-KD by western blot experiment.
Conclusions
In summary, our study identified that DAB2IP has a role in predicting metastasis and poor survival in NSCLC. DAB2IP could regulate metastasis by governing cell-matrix and cell-cell adhesion.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.