目的：研究肺腺癌组织中长链非编码RNA（long non-coding RNA，lncRNA）肌联蛋白反义RNA1(titin antisense RNA 1，TTN-AS1)的表达情况，并分析其与肺腺癌患者临床病理特征和预后的关系。方法：使用TCGA数据库对肺腺癌数据集中TTN-AS1 的表达情况进行分析；收集在2014 年1 月至2015 年1 月期间在河北医科大学第四医院胸外科行肿瘤切除并经病理证实的52 例肺腺癌患者肿瘤组织及其相应癌旁组织标本，使用qPCR检测其TTN-AS1 的表达水平并分析其与患者临床病理特征的相关性，生存分析探讨其在患者预后中的临床意义。结果：TCGA数据库分析和qPCR检测结果均显示，TTN-AS1 在肺腺癌组织中的表达水平显著高于癌旁组织（均P<0.01）。TTN-AS1 的表达与肺腺癌患者的TNM分期和淋巴结转移相关联（均P<0.05），而与患者性别、年龄、肿瘤侵犯范围无关联（P>0.05）。Kaplan-Meier 单因素分析结果显示，高表达TTN-AS1 较低表达TTN-AS1 的肺腺癌患者术后DFS和OS显著缩短（均P<0.01）。Cox 比例风险回归模型分析结果显示，肿瘤高侵犯范围、阳性淋巴结转移和TTNAS1高表达是影响患者术后PFS 和OS的独立危险因素（P<0.01）。结论：TTN-AS1 在肺腺癌组织中高表达，与患者TNM分期、淋巴结转移以及与患者较差的DFS 和OS 密切关联（均P<0.05），高表达TTN-AS1 可能是提示肺腺癌患者预后不良的生物标志物。

Objective：To study the expression of long non-coding RNA (lncRNA) titin antisense RNA 1 (TTN-AS1) in lung adenocarcinoma (LUAD) tissues, and explore its relationship with clinicopathologic characteristics and prognosis of LUAD patients. Methods:The TTN-AS1 expression in LUAD data set was analyzed using TCGA database. 52 pairs of tumor tissues and matched para-carcinoma tissues from LUAD patients, who underwent surgical resection and were later pathologically conformed in Fourth Hospital of Hebei Medical University between Jan. 2014 and Jan. 2015, were used in this study. qPCR was performed to detect TTN-AS1 expression in the specimens. Then, the correlations between TTN-AS1 expression and clinicopathologic characteristics were analyzed. Survival analysis was used to determine the significance of TTN-AS1 expression for predicting the prognosis of LUAD patients. Results: TCGA database analysis and qPCR results showed that TTN-AS1 expression in LUAD tissues was significantly higher than that in normal lung and para-carcinoma tissues (both P<0.01). TTN-AS1 expression in LUAD tissues was significantly correlated with the TNM stage and lymph node metastasis (P<0.05), but not correlated with gender, age, tumor invasion range (P>0.05). Kaplan-Meier univariate analysis result demonstrated that the patients with high TTN-AS1 expression had shorter post-operative disease-free survival (DFS) and overall survival (OS) than those patients with low TTN-AS1 expression (all P<0.01). Cox proportional hazard regression model result demonstrated that wider tumor invasion range, positive lymph node metastasis and high TTN-AS1 expression were significantly correlated with shorter postoperative DFS and OS (P<0.05). Conclusion: TTN-AS1 was highly expressed in LUAD tissues, and closely correlated with TNM stage and lymph node metastasis of LUAD patients (all P<0.05). High expression of TTN-AS1 is significantly correlated with shorter DFS and OS, indicating that TTN-AS1 may be a biomarker for predicting poor prognosis of LUAD patients.

国家自然科学基金资助项目（No. 81871894）；河北省自然科学基金资助项目（No. H2018206318）