Dataset Information

The long non-coding RNA NONHSAG026900 predicts prognosis as a favorable biomarker in patients with diffuse large B-cell lymphoma.

ABSTRACT: Long non-coding RNAs are known to be involved in cancer progression, but their biological functions and prognostic values are still largely unexplored in diffuse large B-cell lymphoma. In this study, long non-coding RNAs expression was characterized in 1,403 samples including normal and diffuse large B-cell lymphoma by repurposing 7 microarray datasets. Compared with any stage of normal B cells, NONHSAG026900 expression was significantly decreased in tumor samples. And in germinal center B-cell subtype, the significantly higher expression of NONHSAG026900 indicated it was a favorable prognosis biomarker. Then the prognostic power of NONHSAG026900 was validated with another independent dataset and NONHSAG026900 improved the predictive power of International Prognostic Index as an independent factor. Moreover, functional prediction and validation demonstrated that NONHSAG026900 could inhibit cell cycle activity to restrain tumor proliferation. These findings identified NONHSAG026900 as a novel prognostic biomarker and offered a new therapeutic target for diffuse large B-cell lymphoma patients.

SUBMITTER: Zhao S

PROVIDER: S-EPMC5470975 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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The long non-coding RNA NONHSAG026900 predicts prognosis as a favorable biomarker in patients with diffuse large B-cell lymphoma.

Zhao Shuangtao S Fang Shuangsang S Liu Yanhua Y Li Xixi X Liao Shengyou S Chen Jinwen J Liu Jingjia J Zhao Lianhe L Li Hui H Zhou Wei W Shen Wenzhi W Dong Xiaoli X Xiang Rong R Wang Luhua L Zhao Yi Y

Oncotarget 20170501 21

Long non-coding RNAs are known to be involved in cancer progression, but their biological functions and prognostic values are still largely unexplored in diffuse large B-cell lymphoma. In this study, long non-coding RNAs expression was characterized in 1,403 samples including normal and diffuse large B-cell lymphoma by repurposing 7 microarray datasets. Compared with any stage of normal B cells, NONHSAG026900 expression was significantly decreased in tumor samples. And in germinal center B-cell ...[more]

PMID: 28423735

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Project description:BackgroundDiffuse large B-cell lymphoma (DLBCL) is an aggressive and complex disease characterized by wide clinical, phenotypic and molecular heterogeneities. The expression pattern and clinical implication of long non-coding RNAs (lncRNAs) between germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes in DLBCL remain unclear. This study aims to determine whether lncRNA can serve as predictive biomarkers for subtype classification and prognosis in DLBCL.MethodsGenome-wide comparative analysis of lncRNA expression profiles were performed in a large number of DLBCL patients from Gene Expression Omnibus (GEO), including GSE31312 cohort (N = 426), GSE10846 (N = 350) cohort and GSE4475 cohort (N = 129). Novel lncRNA biomarkers associated with clinically molecular subtype and prognosis were identified in the discovery cohort using differential expression analyses and weighted voting algorithm. The predictive value of the lncRNA signature was then assessed in two independent cohorts. The functional implication of lncRNA signature was also analyzed by integrative analysis of lncRNA and mRNA.ResultsSeventeen of the 156 differentially expressed lncRNAs between GCB and ABC subtypes were identified as candidate biomarkers and integrated into form a lncRNA-based signature (termed SubSigLnc-17) which was able to discriminate between GCB and ABC subtypes with AUC of 0.974, specificity of 89.6% and sensitivity of 92.5%. Furthermore, subgroups of patients characterized by the SubSigLnc-17 demonstrated significantly different clinical outcome. The reproducible predictive power of SubSigLnc-17 in subtype classification and prognosis was successfully validated in the internal validation cohort and another two independent patient cohorts. Integrative analysis of lncRNA-mRNA suggested that these candidate lncRNA biomarkers were mainly related to immune-associated processes, such as T cell activation, leukocyte activation, lymphocyte activation and Chemokine signaling pathway.ConclusionsOur study uncovered differentiated lncRNA expression pattern between GCB and ABC DLBCL and identified a 17-lncRNA signature for subtype classification and prognosis prediction. With further prospective validation, our study will improve the understanding of underlying molecular heterogeneities in DLBCL and provide candidate lncRNA biomarkers in DLBCL classification and prognosis.

Project description:Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) is a highly heterogeneous type of non-Hodgkin lymphoma. A number of studies have demonstrated that microRNA-130a (miR-130a) serves a role in the tumorigenesis and prognosis of numerous human tumors. However, to the best of our knowledge, the prognostic significance of miR-130a in PGI-DLBCL remains unknown. The present study explored the association between miR-130a and the clinical outcomes of PGI-DLBCL. Relative miR-130a expression was assessed by reverse transcription-quantitative PCR. Immunohistochemistry was used to detect expression levels of BCL-2, c-MYC, neprilysin, B-cell lymphoma 6 protein, PWWP domain-containing DNA repair factor 3A and proliferation marker protein Ki-67. A receiver operating characteristic curve was constructed to analyze the specificity and sensitivity of microRNA levels in the diagnosis of PGI-DLBCL. Survival curves were constructed using the Kaplan-Meier method. In the present study, miR-130a expression was notably higher in patients with PGI-DLBCL compared with in the controls (P<0.0001). miR-130a overexpression was closely associated with a high International Prognostic Index score (3–5) and drug resistance (P=0.017 and P=0.044, respectively). No significant difference in other clinical features was observed. Patients with increased expression levels of miR-130a had lower overall survival [hazard ratio (HR), 2.998; 95% CI, 1.347-6.673; P=0.007] and progression-free survival (HR, 3.325; 95% CI, 1.488-7.429; P=0.003) compared with patients who had lower expression levels of miR-130a. Furthermore, multivariate Cox regression analysis suggested that miR-130a was a negative prognostic parameter in PGI-DLBCL. Therefore, upregulation of miR-130a could become a potential prognostic marker for PGI-DLBCL. Additionally, further study of these results may have important guiding significance for the prognosis of patients with PGI-DLBCL in the clinical setting.

Dataset Information

The long non-coding RNA NONHSAG026900 predicts prognosis as a favorable biomarker in patients with diffuse large B-cell lymphoma.

Publications

The long non-coding RNA NONHSAG026900 predicts prognosis as a favorable biomarker in patients with diffuse large B-cell lymphoma.

Similar Datasets

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