Long noncoding RNA MALAT1 can serve as a valuable biomarker for prognosis and lymph node metastasis in various cancers: a meta-analysis
Although these long noncoding transcripts were once considered to be simply transcriptional noise or cloning artifacts, numerous studies have suggested that lncRNAs are emerging as new players in diverse human diseases, especially cancers (Young and Ponting 2013; Qi and Du 2013). Many studies have demonstrated that lncRNAs are involved in various biological processes, including modulation of apoptosis and proliferation, drug resistance, the process of EMT, cancer progression and metastasis (Hajjari et al. 2014; Yang et al. 2014). An increasing number of studies have focused on the involvement of lncRNAs in cancer development and progression, and proposed them as potential biomarkers for cancer diagnosis or potential targets for cancer therapy (Cui et al. 2016; Yuan et al. 2016; Xie et al. 2016; Liz and Esteller 2016).
MALAT1, regarded as one of the most familiar oncogenic lncRNAs, was overexpressed in various cancers (Yoshimoto et al. 2016). MALAT1 could promote tumor progression through multiple mechanisms in various types of cancer. Increasing reports have demonstrated that MALAT1 could function as a promoter of cell proliferation and metastasis (Thum and Fiedler 2014). Jiao et al. reported that MALAT1 could possibly inhibit G2/M cell cycle arrest, thus promoting EMT in pancreatic cancer (Jiao et al. 2014). Then, Yao et al. found that MALAT1 knockdown induced a decrease in proliferation-enhanced apoptosis, inhibited invasion, and reduced colony formation and led to cell cycle arrest at the G2/M phase in esophageal squamous cell carcinoma (Yao et al. 2016). Xu et al. (2016) revealed that MALAT1 promotes the proliferation of chondrosarcoma cell by activating Notch-1 pathway. Besides, Ji et al. 2013 demonstrated that resveratrol could inhibit invasion and metastasis of colorectal cancer cells though MALAT1 mediated Wnt/beta-catenin pathway . However, the mechanisms underlying aberrant expression of MALAT1 in cancers remain elusive. Some researcher discovered that upregulation of MALAT1 was mediated by the transcription factor Sp1 in A549 lung cancer cells (Li et al. 2015). Additionally, Wang et al. found that silencing of MALAT1 by miR-101 and miR-217 inhibited proliferation, migration, and invasion of esophageal cacner cells (Wang et al. 2015).
Recent studies found that overexpression of MALAT1 correlated with poor prognosis of patients with nearly all types of cancer (Zheng et al. 2014; Zhang et al. 2015; Wang et al. 2016). However, the perplexity and inconsistence arise from a wide range of studies due to heterogeneity. Therefore, a meta-analysis of 2094 cancer patients from 17 studies was undertaken to assess the prognostic value of MALAT1 expression in this study. The pooled data revealed that increased MALAT1 expression was significantly associated with poor OS, DFS and RFS, indicating that MALAT1 has been shown to contribute to cancer progression and considered as a promising prog-nostic biomarker for cancer patients. Furthermore, subgroup analysis indicated that region of study (Germany, Japan or China), cancer type (digestive system cancers, urinary system cancers or respiratory system cancers) and sample size (more or less than 100) did not alter the significant predictive value of MALAT1 in OS from various types of cancer. In addition, MALAT1 was originally discovered to be a marker for metastasis development in early stage lung adenocarcinoma (Ji et al. 2003), and more recently it was shown to be a metastasis-related marker both in squamous cell carcinoma of the lung and hepatocellular carcinoma (Schmidt et al. 2011; Lai et al. 2012). In this present study, we further verified that overexpression of MALAT1 is associated with the incidence of lymph node metastasis in many types of cancer.
Some limitations of this meta-analysis should be acknowledged due to the discrete data across these clinical studies. The major limitation of this meta-analysis was that we only included studies reporting HR or survival curves (except the data that cannot be calculated), and consequently some publications reporting on the prognostic value of MALAT1 were excluded, thus the selection bias might be appeared. Secondly, a part of studies, especially in subgroups analyses, was lightly relative. Thirdly, only summarized data rather than individual patient data were used. Fourthly, some of the HRs could not be directly obtained from the primary studies, we reconstruct the survival curves to extract the HR estimates or calculate them using the reported data. Finally, the cut-off value of high and low MALAT1 expression varied in different studies. Therefore, it is possible that our results might overestimate the prognostic effects of abnormal MALAT1 expression on survival and lymph node metastasis in different types of cancer. We believed that more clinical studies should be conducted to evaluate potential prognostic role of MALAT1 in other types of cancer that have not been included.