非小细胞肺癌中 HuR、TTP 和 miR-133b 的表达及其与预后的关系。

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

机构信息

Department of Thoracic Surgery, Yidu Central Hospital of Weifang, Weifang, Shandong Province, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Jan;22(2):430-442. doi: 10.26355/eurrev_201801_14192.

DOI:10.26355/eurrev_201801_14192

PMID:29424924

Abstract

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.

摘要

目的

本研究旨在探讨 HuR、血栓性血小板减少性紫癜（TTP）和微小 RNA 133b（miR-133b）在非小细胞肺癌（NSCLC）患者中的表达水平，并评估其与疾病预后的关系。

方法

收集 2013 年 1 月至 2015 年 7 月期间在潍坊益都中心医院接受治疗的 110 例石蜡包埋和 33 例新鲜冷冻 NSCLC 样本以及匹配的肿瘤旁正常组织对照。29 例患者提供了石蜡包埋和新鲜冷冻组织。采用免疫组织化学法测量 110 例石蜡包埋肿瘤及其配对对照中 HuR 和 TTP 蛋白的表达水平，采用实时荧光定量 PCR 法测量 miR-133b 水平。

结果

随访参数包括治疗反应、复发事件、复发后治疗、无病生存（DFS）和总生存（OS）。HuR 表达在肿瘤与配对对照之间有显著差异（p < 0.0001）。细胞质 HuR 和 TTP 的表达水平与 pTNM 分期相关（p < 0.05）。HuR 和 TTP 表达与其他临床病理因素（性别、年龄、肿瘤大小、病理亚型、分化状态、淋巴结转移、远处转移和肿瘤侵袭性）之间无显著相关性。miR-133b 在石蜡包埋切片中的表达与肿瘤大小（p = 0.015）和分化状态（p = 0.013）相关，但在冷冻组织样本中仅与 pTNM 分期相关（p = 0.032）。在 68 例 HuR 阳性和 42 例 HuR 阴性患者之间，DFS 或 OS 无显著差异（DFS，Log Rank p = 0.712；OS，Log Rank p = 0.220）。然而，miR-133b 高表达和低表达患者之间的 DFS 和 OS 有显著差异（DFS，Log Rank p = 0.048 < 0.05；OS，Log Rank p = 0.025 < 0.05）。这表明 miR-133b 水平可能具有预后价值。