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Journal of Molecular Histology

, Volume 44, Issue 5, pp 545–554 | Cite as

Expression of LINC00312, a long intergenic non-coding RNA, is negatively correlated with tumor size but positively correlated with lymph node metastasis in nasopharyngeal carcinoma

  • Wenling Zhang
  • Chen Huang
  • Zhaojian Gong
  • Yanhua Zhao
  • Ke Tang
  • Xiaoling Li
  • Songqing Fan
  • Lei Shi
  • Xiayu Li
  • Pan Zhang
  • Yanhong Zhou
  • Donghai Huang
  • Fang Liang
  • Xinli Zhang
  • Minghua Wu
  • Li Cao
  • Jieru Wang
  • Yong Li
  • Wei Xiong
  • Zhaoyang Zeng
  • Guiyuan Li
Original Paper

Abstract

The long intergenic non-coding RNA LINC00312, also called NAG7, was first cloned by our group. Our previous studies have found that LINC00312 could inhibit proliferation and induce apoptosis in nasopharyngeal carcinoma (NPC) cells but also stimulate NPC cell invasion. However, the relevance of LINC00312 in NPC progression or in patient outcomes has not been reported. This study aims to assess the possible correlations of LINC00312 expression with NPC progression and its potential prognostic predictive ability in NPC outcomes. A NPC tissue microarray, which included 561 normal and NPC tissue cores, was used to detect LINC00312 expression, and we found that LINC00312 was significantly down-regulated in NPC tissues compared with non-cancerous nasopharyngeal epithelium tissues. Positive expression of LINC00312 was negatively correlated with tumor size (P < 0.001) but positively correlated with lymph node metastasis (P = 0.002). A receiver operating characteristic (ROC) analysis revealed that LINC00312 expression could distinguish non-cancerous patients from NPC patients (P < 0.001, sensitivity: 72.1 %, specificity: 87.7 %). We also found that LINC00312 was strongly negatively correlated with EBER-1, a non-coding RNA transcribed by Epstein-Barr Virus, in NPC (r = −0.384, P < 0.001). In the final logistic regression analysis model, the abnormal expression of LINC00312 and EBER-1 were found to be independent contributors to nasopharyngeal carcinogenesis (P < 0.001, P < 0.001, respectively). A survival analysis revealed that LINC00312 could predict a good prognosis of no lymph node metastasis (Disease Free Survival (DFS): P = 0.005, Overall Survival (OS): P = 0.001) and a poor prognosis of lymph node metastasis (DFS: P = 0.011, OS: P = 0.001) in NPC patients. Low expression of LINC00312 was an independent risk factor for OS in multivariate analyses (P = 0.017). These observations indicated that LINC00312 could represent a potential biomarker for metastasis, progression and prognosis in NPC.

Keywords

LINC00312 Long intergenic non-coding RNA (LincRNA) Nasopharyngeal carcinoma (NPC) Prognosis Epstein-barr virus (EBV) 

Abbreviations

NPC

(nasopharyngeal carcinoma)

TMA

(tissue microarray)

ISH

(in situ hybridization)

ROC

(receiver operating characteristic)

LincRNA

Long intergenic non-coding RNA

EBV

Epstein-barr virus

Notes

Acknowledgments

This work was supported by the National High Technology Research and Development Program of China (Grant No. 2012AA02A206), the National Natural Science Foundation of China (Grant Nos. 81210408007, 81071644, 81172189, 81171930, 81272298, 81272975 and 91229122), the Hunan Province Natural Science Foundation of China (Grant Nos. 10JJ7003, 12JJ2044), the Hunan Province Science and Technology Foundation of China (Grant No. 2012FJ6073), the Innovative Training Project of Central South University (Grant No. YC12422).

Conflict of interest

  We declare that we have no conflicts of interest.

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Wenling Zhang
    • 1
    • 2
  • Chen Huang
    • 2
  • Zhaojian Gong
    • 2
  • Yanhua Zhao
    • 1
  • Ke Tang
    • 2
  • Xiaoling Li
    • 2
  • Songqing Fan
    • 3
  • Lei Shi
    • 3
  • Xiayu Li
    • 4
  • Pan Zhang
    • 5
  • Yanhong Zhou
    • 2
  • Donghai Huang
    • 6
  • Fang Liang
    • 2
  • Xinli Zhang
    • 1
  • Minghua Wu
    • 2
  • Li Cao
    • 2
  • Jieru Wang
    • 7
  • Yong Li
    • 8
  • Wei Xiong
    • 2
    • 4
    • 9
  • Zhaoyang Zeng
    • 2
    • 4
    • 9
  • Guiyuan Li
    • 2
    • 4
    • 9
  1. 1.Department of Medical Laboratory Science, Xiangya School of MedicineCentral South UniversityChangshaChina
  2. 2.Key Laboratory of Carcinogenesis of Ministry of Health, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research InstituteCentral South UniversityChangshaChina
  3. 3.Department of Pathology, the Second Xiangya HospitalCentral South UniversityChangshaChina
  4. 4.Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, the Third Xiangya HospitalCentral South UniversityChangshaChina
  5. 5.Department of Infectious Disease, the Third Xiangya HospitalCentral South UniversityChangshaChina
  6. 6.Ear-Nose-Throat department, Xiangya HospitalCentral South UniversityChangshaChina
  7. 7.Department of MedicineNational Jewish HealthDenverUSA
  8. 8.Department of Biochemistry and Molecular Biology, School of Medicine, Center for Genetics and Molecular MedicineUniversity of LouisvilleLouisvilleUSA
  9. 9.Tumor Hospital, Xiangya School of MedicineCentral South UniversityChangshaChina

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