WTAP overexpression tied to poor outcomes in NSCLC

High expression of Wilms’ tumor 1-associating protein (WTAP) in patients with nonsmall cell lung cancer (NSCLC) appears to promote poor clinical outcomes, suggests a study.

This retrospective analysis was carried out on tumour tissues and surrounding nontumour tissues of 150 patients with NSCLC surgically resected from January 2016 to January 2018. Immunochemistry was used to detect the expression of WTAP in NSCLC tissues.

The authors performed univariate and multivariate Cox regression analyses on clinicopathologic parameters to determine the predictors for overall survival (OS) time. They also conducted MTS, colony formation, and transwell assays to estimate cell proliferation, migration, and invasion.

In addition, Western blot analysis and RT-qPCR were used to assess the association between WTAP and the cell migration and invasion marker-related proteins. WTAP expression was “knocked-down in cell lines by shRNA,” while the pathways regulated by WTAP were examined via RNA-Seq.

There was high expression of WTAP in tumour tissues among patients with NSCLC. The higher expression significantly predicted poor OS (p<0.01). Moreover, the overexpression of WTAP could potentially promote cell proliferation, migration, and invasion (p<0.01), while knocked-down WTAP reduced such effects (p<0.01) when compared with the control group in vitro.

In a mouse model, higher expression of WTAP also promoted tumour enlargement relative to the control group (p<0.01), while knocked-down WTAP prevented the expression of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) in cell lines (p<0.01).

“Besides, in NSCLC, knocked-down CEACAM5 significantly reduced the impact of WTAP on cell proliferation, migration, and invasion compared with the control group (p<0.05),” the authors said.

“CEACAM5 may play a synergistic role with WTAP to jointly promote NSCLC progression by enhancing cell proliferation, invasion, and migration,” they noted.