HuR, TTP, and miR-133b expression in NSCLC and their association with prognosis

摘要

OBJECTIVE: This study sought to explore HuR, Thrombotic Thrombocytopenic Purpura (TTP), and microRNA 133b (miR-133b) expression levels in non-small cell lung cancer (NSCLC) patients and assess the relationship of expression with disease prognosis. PATIENTS AND METHODS: One hundred and ten paraffin-embedded and 33 fresh flash-frozen NSCLC samples, together with matched tumor adjacent normal tissue controls, were collected from patients between January 2013 and July 2015 in Yidu Central Hospital of Weifang. Twenty-nine patients provided both paraffin-embedded and fresh frozen tissues. HuR and TTP protein expression levels were measured in 110 paraffin-embedded tumors and matched controls using immunohistochemistry, while miR-133b levels were measured using Real-time fluorescent quantitative PCR. RESULTS: Follow-up parameters included treatment response, relapse events, post-relapse treatment, disease free survival (DFS), and overall survival (OS). HuR expression was significantly different between tumor and matched controls (p < 0.0001). Cytoplasmic expression levels of HuR and TTP correlated with pTNM staging (p < 0.05). No significant correlation was observed between HuR and TTP expression and other clinical pathological factors (gender, age, tumor size, pathological subtype, differentiation status, lymph node metastasis, distant metastasis, and tumor invasiveness). MiR-133b expression correlated with tumor size (p = 0.015) and differentiation status (p = 0.013) in paraffin-embedded sections, but was only correlated with pTNM staging (p = 0.032) in frozen tissue samples. No significant difference in DFS nor OS was observed between 68 HuR-positive and 42 HuR-negative patients (DFS, Log Rank p = 0.712; OS, Log Rank p = 0.220). However, DFS and OS were significantly different between miR-133b high-expression and low-expression patients (DFS, Log Rank p = 0.048 < 0.05; OS, Log Rank p = 0.025 < 0.05). This indicates that miR-133b levels may have prognostic value. CONCLUSIONS: HuR expression was negatively correlated with TTP expression in NSCLC tissues. MiR-133b levels were downregulated in normal tissues compared to both paraffin and frozen tumor samples, and correlated with both HuR and TTP expression, which may affect the prognosis of NSCLC patients.