Abstract
Background: Metastasis is a severe problem in patients with oral squamous cell carcinoma (OSCC), which is the fifth most common cancer worldwide. Leukemia inhibitory factor (LIF) has been studied in different cancers, while the role of LIF in OSCC remains unclear. Methods: LIF expression was detected in 100 OSCC samples by immunohistochemistry. Effects of LIF on cell motility were evaluated in OSCC cell lines. High-throughput microarray analysis was also conducted. The correlation between LIF and the downstream effector was analyzed by real-time quantitative reverse transcription PCR. Results: Patients with OSCC who had lymph node metastasis or advanced cancer stages showed high LIF expression. OSCC patients with higher LIF expression, advanced stage, large tumor size, or lymph node metastasis had significantly shorter overall survival. LIF regulated cancer cell motilities through outside-in signaling. The inhibin beta A subunit (INHBA) gene was identified as a crucial downstream effector of LIF-promoted OSCC progression and restored migration and invasion abilities in LIF knockdown transfectants. Conclusion: LIF enhances regional lymphatic spread, thus leading to an advanced cancer stage. Regulation of LIF downstream molecules such as INHBA inhibits the invasion or migration ability of cancer cells. Thus, LIF can be a potential target in preventing cancer metastasis and spread.
Highlights
Oral cancer is the sixth leading cause of malignant tumor mortality and is an important healthcare problem worldwide [1]
We found a significant association of Leukemia inhibitory factor (LIF) protein expression and other clinicopathological variables such as depth of invasion (p = 0.001) and surgical margins (p = 0.023)
Kaplan–Meier curves showed that oral squamous cell carcinoma (OSCC) patients with higher LIF expression, advanced stage, large tumor size, or positive lymph node metastasis had significantly shorter overall survival (p < 0.001, p = 0.011, p = 0.002, and p = 0.014, respectively; log-rank test) than others
Summary
Oral cancer is the sixth leading cause of malignant tumor mortality and is an important healthcare problem worldwide [1]. Metastasis is a severe problem in patients with oral squamous cell carcinoma (OSCC), which is the fifth most common cancer worldwide. Results: Patients with OSCC who had lymph node metastasis or advanced cancer stages showed high LIF expression. OSCC patients with higher LIF expression, advanced stage, large tumor size, or lymph node metastasis had significantly shorter overall survival. The inhibin beta A subunit (INHBA) gene was identified as a crucial downstream effector of LIF-promoted OSCC progression and restored migration and invasion abilities in LIF knockdown transfectants. Regulation of LIF downstream molecules such as INHBA inhibits the invasion or migration ability of cancer cells. LIF can be a potential target in preventing cancer metastasis and spread
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