LincRNA-p21 predicts favorable clinical outcome and impairs tumorigenesis in diffuse large B cell lymphoma patients treated with R-CHOP chemotherapy

Clin Exp Med. 2017 Feb;17(1):1-8. doi: 10.1007/s10238-015-0396-8. Epub 2015 Oct 16.

Abstract

Despite improved survival for the patients with diffuse large B cell lymphoma (DLBCL), the prognosis after relapse is poor. LincRNA-p21 is a long intergenic noncoding RNA, which is located on chromosome 17, approximately 15 kb upstream from the Cdkn1a (p21) gene. However, its clinical importance and biological role in DLBCL prognosis are unknown. In this study, we conducted quantitative reverse-transcription polymerase chain reaction to investigate the lincRNA-p21 expression in DLBCL. We found that lincRNA-p21 levels were markedly decreased in DLBCL tissues compared with normal. Its expression level was significantly correlated with Ann Arbor stages, B symptoms, performance status, IPI score and serum LDH. Moreover, patients with high levels of LincRNA-p21 expression had a favorable overall survival and progression-free survival. Furthermore, ectopic expression of lincRNA-p21 inhibited cell proliferation, arrested cycle progression and modulated cyclin D1, CDK4 and p21 expression in DLBCL cell lines. These results demonstrated lincRNA-p21 can be identified as a potential novel prognostic biomarker for prognosis in DLBCL and regulate cell proliferation and cycle in vitro. Our findings highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL.

Keywords: Biomarker; Diffuse large B cell lymphoma; LincRNA-p21; Long noncoding RNAs; Prognosis.

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / drug effects
  • Carcinogenesis / genetics*
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • L-Lactate Dehydrogenase / blood
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Prednisone / therapeutic use
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Recurrence
  • Rituximab
  • Signal Transduction
  • Survival Analysis
  • Vincristine / therapeutic use

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers, Tumor
  • CCND1 protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • R-CHOP protocol
  • RNA, Long Noncoding
  • Cyclin D1
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • L-Lactate Dehydrogenase
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Prednisone