Abstract
Dysregulation of the long noncoding RNA antisense noncoding RNA in the INK4 locus (ANRIL) has been reported in various solid tumors. We performed a synthetic analysis to clarify the clinical value of ANRIL as a prognostic indicator in malignant tumors. Article collection was conducted using several electronic databases, including PubMed, Web of Science, Medline, OVID and Embase (up to July 14 2017). Thirteen original studies and 1172 total patients were included in the meta-analysis. There was a significant positive association between the high expression level of ANRIL and lymph node metastasis (OR = 4.77, 95% CI: 2.30–9.91, P < 0.001) by a random effects model (I2 = 73.2, P = 0.001) and negative association with poor grade cancer (OR = 3.44, 95% CI: 1.68–7.08) by a random-effects model (I2 = 77.9, P = 0.000). The results of the meta-analysis showed that overexpression of ANRIL is positively related to poor overall survival (OS) (pooled HR = 2.12, 95% CI: 1.78–2.53, P < 0.0001) by a fixed-effects model (I2 = 0%, P = 0.654) and poor disease-free survival (DFS) (HR = 2.10, 95% CI: 1.51–2.92, P < 0.001) by a fixed-effects model (I2 = 13.3%, P = 0.315) in human solid cancers. Statistically significant associations were also found with cancer type, analysis method, sample size, and follow-up time. In conclusion, ANRIL may serve as a novel biomarker for indicating lymph node metastasis and prognosis in human cancer.
Highlights
Owing to its increasing incidence and associated mortality, cancer is becoming the leading cause of death and represents a major public health concern worldwide
The Long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) is up-regulated in a variety of malignant tumors, acting as a novel oncogene in tumorigenesis and progression, promoting tumor cell proliferation, apoptosis, and metastasis, and reducing survival [19, 22, 23, 29, 30]
We investigated the association between the expression of ANRIL and clinicopathological features; our meta-analysis showed that www.impactjournals.com/oncotarget overexpression of ANRIL is strongly associated with lymph node metastasis (LNM) (OR = 4.77, 95% confidence intervals (CI): 2.30–9.91, P < 0.001) and clinical stage (OR = 3.44, 95% CI: 1.68–7.08, P < 0.001), whereas there was no significant association between high ANRIL expression and histological grade (OR = 1.42, 95% CI: 0.32– 6.27, P = 0.646) or tumor size (OR = 1.77, 95% CI: 0.63– 4.93, P = 0.278)
Summary
Owing to its increasing incidence and associated mortality, cancer is becoming the leading cause of death and represents a major public health concern worldwide. An estimated 4292,000 new cancer cases and 2814,000 cancer deaths will occur in 2015 in China [1, 2] Clinical treatments such as surgery, chemotherapy, radiotherapy, targeted therapy, or other comprehensive treatments can improve the prognosis of patients with cancer [3], the 5-year survival rate remains low owing to the malignant progression of tumors [4] and the lack of effective early diagnostic methods. Long noncoding RNA (lncRNA) are mRNA-like transcripts with a length of more than 200 nucleotides that lack an open reading frame [5] Such transcripts were originally considered as genomic “noise” [6]; increasing evidence suggests that lncRNAs act as critical regulators in diverse diseases and cellular processes, such as the regulation of gene expression regulation and post-translational processing [7,8,9]. Several lncRNAs are involved in tumor proliferation, migration, and invasion, of which some are www.impactjournals.com/oncotarget considered as representing promising prognostic markers [14,15,16]
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