Expression of STAT3 and vasculogenic mimicry in gallbladder carcinoma promotes invasion and metastasis

Exp Ther Med. 2021 Jul;22(1):738. doi: 10.3892/etm.2021.10170. Epub 2021 May 9.

Abstract

Surgical treatment of gallbladder carcinoma remains challenging, while targeted therapy has been demonstrated to have potential. In the present study, the effect of signal transducer and activator of transcription 3 (STAT3) expression and vasculogenic mimicry (VM) on the occurrence and development of gallbladder carcinoma was evaluated. A total of 72 patients with gallbladder carcinoma and 10 patients with chronic cholecystitis were examined. Immunohistochemical staining was performed to determine the positive expression rates of STAT3. Periodic acid Schiff CD34 double staining was performed to detect VM in the gallbladder carcinoma group. STAT3 expression and VM in gallbladder carcinoma tissues was compared among patients with different clinical characteristics. In postoperative patients with gallbladder cancer, the relationship of the postoperative recurrence time with STAT3 expression and VM was assessed. STAT3 expression in gallbladder carcinoma tissue was significantly higher than that in cholecystitis tissue (P<0.05). STAT3 expression levels and VM were positively correlated in gallbladder carcinoma tissue. STAT3 protein expression in gallbladder carcinoma tissues differed significantly among patients with different degrees of differentiation and clinical stages (P<0.05). Among the 51 patients who completed the 3-year follow-up, the mean time to relapse was 17.353 and 35.647 months in those with high and low STAT3 expression, respectively, with significant differences (P<0.05). The VM structure was detected in 47 cases (92.15%) and not detected in four cases (7.84%), which exhibited no immediate recurrence after surgery, and the difference in the mean postoperative recurrence time was significant (22.38 vs. 36.00 months, respectively; P<0.05). In gallbladder carcinoma tissues, a lower degree of differentiation, higher malignancy degree and higher clinical stage were associated with higher expression of STAT3 and VM. Thus, STAT3 may promote VM formation in the process of tumor occurrence, development and metastasis. Therefore, STAT3 as a regulatory target, may inhibit the proliferation and invasion of tumor cells and block the development of VM, thereby representing a suitable target for antitumor angiogenesis therapy.

Keywords: STAT3; endothelial-dependent vessel; gallbladder carcinoma; tumor development; vasculogenic mimicry.

Grants and funding

Funding: This work was supported by a grant from The Fifth Affiliated Hospital of the Medical School of Nantong University (Taizhou, China; grant no. ZL201931).