In China, lung cancer is considered as a lethal disease due to its high mortality . Despite the advances in treatments of lung cancer, the outcomes of lung cancer are still not ideal . The poor prognosis may be attributed to early relapse and metastasis . The mechanisms for tumor metastasis remain unclear . A variety of parameters are applied to predict tumor progression of lung cancer, such as performance status, disease stage, and weight loss. However, the effects were far from satisfactory . Thus, it is essential to explore novel biomarker for prognosis and treatment of lung cancer.
LncRNAs are a class of long non-coding RNAs, which have been reported to play regulatory roles in gene expression, ligand-receptor engagement and RNA splicing [25, 26]. Recently studies suggested that lncRNAs were involved the initiation, response to therapy and progression of a variety of human cancers [27, 28]. Meanwhile, some lncRNAs have ever been reported to take part in development and progression of lung cancer. XIST was an oncogenic lncRNA in NSCLC, and its elevated expression level represented shorter survival and poor prognosis . LncRNA GAS5-AS1 was down-regulated in NSCLC tissue specimens, and correlated with tumor size, TNM stage, and metastasis, suggesting its inhibitory roles in malignant development of the cancer . Over-expression of lncRNA HOTAIR showed obvious link with pathological stage and lymph node metastasis of the patients that hold the potential to serve as a prognostic biomarker for lung cancer . All the researches suggested that lncRNAs played pivotal roles in tumorigenesis of lung caner which might be employed as predictors for the cancer.
In this study, we investigated the expression of HOTTIP by qRT-PCR method. The results revealed that the expression of HOTTIP was significantly up-regulated in lung cancer tissue samples compared with the matched noncancerous tissue samples. Moreover, the increased HOTTIP expression showed significant associated with lymph node metastasis and TNM stage. All the data revealed that HOTTIP was an oncogenic lncRNA in lung cancer that promoted aggressive development and progression of the cancer. The conclusion was supported by the previous investigations. The study carried out by Sang et al. reported that HOTTIP was up-regulated in NSCLC tissues. Knockdown of HOTTIP could suppress cell proliferation, migration and invasion in vitro, suggesting its promoting roles in lung cancer progression . However, the oncogentic mechanisms of HOTTIP in the carcinogenesis of lung cancer were far from being full elucidated. Further researches were still needed.
Given its functional roles in tumor progression, HOTTIP was proved to serve as a predictor for several cancers. Ye et al. suggested over-expression of HOTTIP could contribute to initiation and progression of gastric cancer which might be a potential prognostic biomarker for the cancer . In colorectal cancer, up-regulation of HOTTIP presented poor prognosis for patients . Additionally, the predictive function of HOTTIP was also reported in other types of malignancy, like osteosarcoma, tongue squamous cell carcinoma, and hepatocellular carcinoma [32–34]. Based on the previous investigations, we deduced that HOTTIP might be an effective indicator for lung cancer progression. In this study, survival curve was built based on the expression levels of HOTTIP among lung cancer patients. The curve demonstrated that lung cancer patients with low expression of HOTTIP had a longer survival than those with high expression. Cox regression analysis demonstrated that HOTTIP was an independent prognostic factor for lung cancer.