Abstract
Studies published in recent years have demonstrated that abnormal long noncoding RNA (lncRNA) antisense RNA to TP73 gene (TP73-AS1) expression is markedly associated with tumorigenesis, cancer progression and the prognosis of cancer patients. We aimed to explore the prognostic value of TP73-AS1 in multiple cancers. We comprehensively searched PubMed, Embase, Web of Science and the Cochrane Library (up to February 21, 2019). Hazard ratios (HRs), odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were calculated to estimate the association of TP73-AS1 with survival and clinicopathological features. The potential targets and pathways of TP73-AS1 in multiple cancers were summarized. Nineteen studies that involved thirteen types of cancers and 1329 cancer patients were identified as eligible for this meta-analysis. The results showed that high TP73-AS1 expression was significantly correlated with shorter overall survival (OS) (HR = 1.962, 95% CI 1.630-2.362) and disease-free survival (DFS) (HR = 2.050, 95% CI 1.293-3.249). The summary HRs of OS were 2.101 (95% CI 1.516-2.911) for gastric cancer (GC) and 1.920 (95% CI 1.253-2.942) for osteosarcoma. Subgroup analysis of OS demonstrated that the differential expression of TP73-AS1 in cancer tissues was a potential source of heterogeneity. Furthermore, increased TP73-AS1 expression was markedly associated with larger tumor size (OR = 2.759, 95% CI 1.759-4.330), advanced histological grade (OR = 2.394, 95% CI 1.231-4.656), lymph node metastasis (OR = 2.687, 95% CI 1.211-5.962), distant metastasis (OR = 4.145, 95% CI 2.252-7.629) and advanced TNM stage (OR = 2.633, 95% CI 1.507-4.601). The results of Egger’s test and sensitivity analysis verified the robustness of the original results. High TP73-AS1 expression can predict poor survival and poor clinicopathological features in cancer patients and TP73-AS1 might be a potential biomarker and therapeutic target.
Highlights
An antisense RNA to the TP73 gene (TP73-AS1), named KIAA0495/PDAM, is located in the 1p36 chromosome region that is frequently deleted in tumors and comprises tumor suppressor genes[8]
TP73-AS1 can suppress the progression of bladder cancer by epithelial-mesenchymal transition (EMT), and low TP73-AS1 expression predicts a shorter survival of bladder cancer patients[10]
We aimed to explore the potential of TP73-AS1 as a novel biomarker and therapeutic target
Summary
An antisense RNA to the TP73 gene (TP73-AS1), named KIAA0495/PDAM, is located in the 1p36 chromosome region that is frequently deleted in tumors and comprises tumor suppressor genes[8]. Functions as a tumor suppressor by sponging miR-941 at nine high-affinity binding sites[9]. TP73-AS1 can promote hepatocellular carcinoma (HCC) cell proliferation via miR-200a-dependent HMGB1/RAGE regulation, and its high expression level is significantly associated with a poorer prognosis of HCC patients[11]. Knockdown of TP73-AS1 suppresses the proliferation and invasion of osteosarcoma cells by sponging miR-14212. TP73-AS1, which is upregulated in cholangiocarcinoma (CCA) tissues, predicts adverse phenotypes for CCA, and silencing TP73-AS1 attenuates CCA cell proliferation, migration and invasion[13]. We performed this meta-analysis based on studies focusing on the association of TP73-AS1 with survival and clinicopathological features. We aimed to explore the potential of TP73-AS1 as a novel biomarker and therapeutic target
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