Systematic review and meta-analysis of the utility of long non-coding RNA GAS5 as a diagnostic and prognostic cancer biomarker

The growth arrest-specific 5 transcript (GAS5) is a long non-coding RNA (lncRNA) involved in the control of cell cycle progression and apoptosis in a wide variety of cells. To determine the clinical value of GAS5 expression in cancer patients, we performed a systematic review and meta-analysis exploring its association with the diagnosis, prognosis, and clinicopathological characteristics of cancer. Ten articles on prognosis, 15 on clinicopathology, and 5 on diagnosis were analyzed. Overall results showed that decreased GAS5 expression associated with unfavorable overall survival (OS) (HR = 2.50, 95%CI: 1.85-3.38, P < 0.001) and disease-free survival (DFS) (HR = 2.24, 95%CI: 1.58-3.18, P < 0.001) in several tumor types. Down-regulation of GAS5 correlated with poor recurrence-free survival (RFS) in hepatocellular carcinoma (HR = 2.40, 95%CI: 1.27-4.54, P = 0.007), and was associated with lymph node metastasis (OR = 1.92, 95% CI: 1.44-2.57, P < 0.001), distant metastasis (OR = 2.7, 95% CI: 1.05-6.97, P = 0.040), poor clinical stage (OR = 0.26, 95% CI: 0.18-0.38, P < 0.001), larger tumor size (OR = 3.21, 95% CI: 2.08-4.95, P < 0.001), and poor tumor differentiation (OR = 1.98, 95% CI: 1.40-2.80, P < 0.001). Pooled results of diagnostic data analysis showed that GAS5 exhibited a sensitivity of 0.76 and specificity of 0.64 for cancer diagnosis, and an area under the curve of 0.76 (95% CI: 0.72-0.80) indicated moderate diagnostic accuracy. This meta-analysis suggests GAS5 lncRNA may be a useful diagnostic and prognostic cancer biomarker, and may be especially useful for identifying patients prone to developing lymph node or distant metastasis.