Low TIF1γ Expression is Associated with Cancer Aggressiveness and Shorter Recurrence-Free Survival in Patients with Esophageal Squamous Cell Carcinoma.

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is a significant cause of cancer-related death despite advances in multidisciplinary treatment. Transcriptional intermediary factor 1 γ (TIF1γ) has been known to be involved in tumorigenesis and epithelial-mesenchymal transition (EMT), which are linked to cancer aggressiveness and therapeutic resistance. However, its role in ESCC remains unclear. Therefore, we investigated the expression significance and function of TIF1γ in ESCC.

Methods: We used immunohistochemical analysis to investigate the clinical significance of tumoral TIF1γ expression in 131 patients with ESCC. We also performed in vitro analysis using ESCC cell lines to evaluate the effects of TIF1γ suppression on EMT marker expression, migration ability, and 5-fluorouracil (5-FU) sensitivity.

Results: The TIF1γ protein was mainly expressed in the nuclear ESCC cells. Low nuclear TIF1γ expression was associated with the progression of tumor depth and frequent recurrence. Low TIF1γ expression was an independent predictor of recurrence in ESCC. Moreover, suppression of TIF1γ facilitated EMT-like changes, such as high migration ability, E-cadherin suppression, vimentin induction, and 5-FU resistance of ESCC cells.

Conclusions: TIF1γ may be a promising biomarker for predicting patients with ESCC at high risk of recurrence. Therapeutic strategies that induce TIF1γ expression are expected to improve the chemosensitivity and prognosis of high-risk patients with ESCC who have low TIF1γ.