STMN1, a prognostic predictor of esophageal squamous cell carcinoma, is a marker of the activation of the PI3K pathway.

The esophageal squamous cell carcinoma (ESCC) subtype with STMN1 overexpression has a high likelihood of lymphatic metastatic recurrence. However, the underlying mechanism remains to be further elucidated. We assessed the expression level of STMN1 and PTEN in 96 pN0 ESCC patient tissues using immunohistochemistry and western blot analysis. Then, the association between STMN1 overexpression and postoperative lymphatic metastatic recurrence was evaluated. In addition, the relationship between STMN1 and PTEN was also assessed. The results showed that STMN1 expression was significantly higher in tumor tissues (P=0.013). STMN1 overexpression was related to tumor length (P=0.003) and depth of invasion (P=0.019). In addition, STMN1 overexpression was significantly associated with postoperative lymphatic metastatic recurrence in pN0 ESCC patients. Patients with STMN1-overexpressing tumors had a higher 3‑year lymphatic metastatic recurrence rate (P=0.024). Furthermore, in laboratory experiments, STMN1 expression was stably silenced using lentiviral vector delivery of shRNA in Eca109 and EC9706 cell lines to assess the functional effect of STMN1 in vitro. The results indicated that stable silencing of STMN1 expression significantly inhibited cell proliferation, migration and invasion. Moreover, we inactivated the PI3K pathway in ESCC cell lines with the PI3K inhibitor LY294002 and then detected STMN1 expression by western blot analysis. STMN1 levels were robustly reduced consistent with the downregulation of p‑Akt (S473) by PI3K pathway inhibition. STMN1 can act as a marker to quantitatively measure the activation of the PI3K pathway and stratify patients accordingly.