Long noncoding RNA ROR as a novel biomarker for progress and prognosis outcome in human cancer: a meta-analysis in the Asian population

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Long noncoding RNA ROR as a novel biomarker for progress and prognosis outcome in human cancer: a meta-analysis in the Asian population This article was published in the following Dove Press journal: Cancer Management and Research Shengquan Yang 1,2,* Jian Chen 1,* Yang Yu 3,* Deli Li 4 Mengyuan Huang 1 Li Yuan 4 Guoyong Yin 1 1 Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2 Department of Orthopaedics, The No.1 People’s Hospital of Yancheng, Yancheng, Jiangsu, People’s Republic of China; 3Department of Digestion, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4 Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Background: Long intergenic non-protein coding RNA, a regulator of reprogramming (ROR), has been found to play an oncogene role in various human malignant tumors. This meta-analysis aimed to synthesize available data to verify the association between clinical prognosis value and ROR expression level. Materials and methods: We performed a systematic search by using PubMed (Medline), Embase, Cochrane Library, ScienceDirect, Springer, and ISI Web of Knowledge from inception to November 15, 2017. Eleven studies with 903 patients were included in this meta-analysis according to the exclusion and inclusion criteria, and the quality of the publications was assessed by using the Newcastle-Ottawa Scale. Pooled odds ratios (OR) and hazard ratios (HR) with 95% CI were used to describe the effect. Results: The results showed that overexpression of ROR is positively associated with lymph node metastasis (OR=4.472, 95% CI: 3.212–6.225, Z=8.87, P=0.000), tumor invasion depth (OR=9.93, 95% CI: 5.33–18.47, Z=7.24, P<0.001), TNM stage (III/IV vs I/II, OR=2.96, 95% CI: 2.18–4.02, Z=6.95, P<0.001), distant metastasis (OR=3.142, 95% CI: 2.187–4.513, Z=6.20, P<0.001) respectively. Additionally, high expression of ROR was significantly correlated with unfavorable disease-free survival (DFS) (HR=2.74, 95% CI: 1.65–3.82, Z=4.93, P=0.000) and overall survival (OS) (HR=2.09, 95% CI: 1.64–2.54, Z=9.07, P<0.001). Subgroup analysis demonstrated that neither cancer type (digestive or respiratory system) nor sample size (more or less than 100) did not alter the prognostic value of ROR. Furthermore, we performed publication bias and sensitivity analysis in order to examine the stability of meta-analysis of ROR along with OS, which showed that the shape of the funnel plot was nearly symmetrical and the resulting pattern was not significantly influenced while disconnecting each suitable study. Conclusion: In accordance with these results, we suggested that the overexpression of long noncoding RNA ROR could act as a novel biomarker for predicting poor prognosis in different human cancers. Keywords: long noncoding RNA, regulator of reprogramming, ROR, prognosis, cancers, meta-analysis Introduction Correspondence: Li Yuan Department of Biochemistry and Molecular Biology, Nanjing Medical University, 818 Tianyuan Road, Jiangning, Nanjing, Jiangsu 211100, People’s Republic of China Tel +86 025 8686 9326 Fax +86 025 8686 9326 Email Today, cancer has become one of the major public health concerns globally and the leading cause of death.1 Recent statistics indicate an anticipated 1,688,780 new cases of cancer and approximately 600,920 deaths resulting from cancer in 2017 in the United States. In China, approximately 4,292,000 new cancer cases were estimated to occur along with an estimated 2,814,000 deaths in 2015.2,3 Until now, scientific advancements have allowed us to better understand the molecular mechanism of oncogenesis, submit your manuscript | www.dovepress.com Cancer Management and Research 2018:10 4641–4652 Dovepress © 2018 Yang et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/CMAR.S174143 4641 Dovepress Yang et al progression, and resistance of cancer. However, the evaluation of tumor prognostics, as well as the predictive factors, are still limited to traditional classifications such as anatomic staging, histological typing, and grading. It is widely considered that the new molecular classification algorithm and personalized, accurate medicine are the complements of time-honored classification, primarily as reflected in the eighth edition of AJCC Cancer Staging Manual.4 Therefore, recent studies are devoted to establishing new potential biomarkers for improving the survival of cancer patients. The human genome is knowingly made up of a vast majority of non-coding RNAs and only approximately 2% proteincoding genes.5 The long non-coding RNAs (lncRNAs) include a group of transcripts in excess of 200 nucleotides with a limited number of protein-coding prospects. They are also deficient in a palpable open reading frame (ORF). Many recent studies have exhibited that lncRNAs might significantly contribute to biological processes such as cellular development and differentiation and to a variety of disease states.6,7 In addition, the deregulation expression of lncRNAs has been shown in multiple types of cancers.8,9 Mechanistic investigation indicated that lncRNAs regulating gene expression through binding to a transcription factor,10 chromatin modifying factors11,12 or heterogeneous nuclear ribonucleoproteins (hnRNPs)13,14 in the cellular nucleus while acting as an endogenous microRNA “sponge” to take part in the target gene’s post-transcriptional regulation processing in the cytoplasm. In addition, some lncRNAs exhibit distinct developmental, tissue-specific expression patterns and the ability to transduce higher-order spatial information.15–17 All these characteristics made lncRNAs potential for application of cancer patient diagnosis and prognosis, along with serving as a possible therapeutic target. Long noncoding RNA, regulator of reprogramming (ROR) is 2,591 nts long and is situated at 18q21.31. It also comprises four exons and was first known to promote reprogrammi (...truncated)