Comprehensive analysis of lncRNA expression profiles reveals a novel lncRNA signature to discriminate nonequivalent outcomes in patients with ovarian cancer

被引:113
作者
Zhou, Meng [1 ]
Sun, Yanying [2 ]
Sun, Yifan [1 ]
Xu, Wanying [1 ]
Zhang, Zhaoyue [1 ]
Zhao, Hengqiang [1 ]
Zhong, Zhaohua [2 ]
Sun, Jie [1 ]
机构
[1] Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin 150081, Peoples R China
[2] Harbin Med Univ, Dept Microbiol, Harbin 150081, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
long non-coding RNAs; ovarian cancer; outcome; BRCA1/2; LONG NONCODING RNA; GENE-EXPRESSION; MUTATOR PHENOTYPE; FUNCTIONAL-ROLE; POOR-PROGNOSIS; SURVIVAL; PREDICTION; METASTASIS; BREAST; BIOINFORMATICS;
D O I
10.18632/oncotarget.8653
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
There is growing evidence of dysregulated long non-coding RNAs (lncRNAs) serving as potential biomarkers for cancer prognosis. However, systematic efforts of searching for an expression-based lncRNA signature for prognosis prediction in ovarian cancer (OvCa) have not been made yet. Here, we performed comprehensive analysis for lncRNA expression profiles and clinical data of 544 OvCa patients from The Cancer Genome Atlas (TCGA), and identified an eight-lncRNA signature with ability to classify patients of the training cohort into high-risk group showing poor outcome and low-risk group showing significantly improved outcome, which was further validated in the validation cohort and entire TCGA cohort. Multivariate Cox regression analysis and stratified analysis demonstrated that the prognostic value of this signature was independent of other clinicopathological factors. Associating the outcome prediction with BRCA1 and/or BRCA2 mutation revealed a superior prognosis performance both in BRCA1/2-mutated and BRCA1/2 wild-type tumors. Finally, a significantly correlation was found between the lncRNA signature and the complete response rate of chemotherapy, suggesting that this eight-lncRNA signature may be a measure to predict chemotherapy response and identify platinum-resistant patients who might benefit from other more efficacious therapies. With further prospective validation, this eight-lncRNA signature may have important implications for outcome prediction and therapy decisions.
引用
收藏
页码:32433 / 32448
页数:16
相关论文
共 86 条
  • [1] Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment
    Alizadeh, Ash A.
    Gentles, Andrew J.
    Alencar, Alvaro J.
    Liu, Chih Long
    Kohrt, Holbrook E.
    Houot, Roch
    Goldstein, Matthew J.
    Zhao, Shuchun
    Natkunam, Yasodha
    Advani, Ranjana H.
    Gascoyne, Randy D.
    Briones, Javier
    Tibshirani, Robert J.
    Myklebust, June H.
    Plevritis, Sylvia K.
    Lossos, Izidore S.
    Levy, Ronald
    [J]. BLOOD, 2011, 118 (05) : 1350 - 1358
  • [2] [Anonymous], TUMOUR BIOL
  • [3] [Anonymous], 2015, J EXP CLIN CANC RES, DOI DOI 10.1186/S13046-014-0119-0
  • [4] [Anonymous], ONCOTARGET
  • [5] Integrated genomic analyses of ovarian carcinoma
    Bell, D.
    Berchuck, A.
    Birrer, M.
    Chien, J.
    Cramer, D. W.
    Dao, F.
    Dhir, R.
    DiSaia, P.
    Gabra, H.
    Glenn, P.
    Godwin, A. K.
    Gross, J.
    Hartmann, L.
    Huang, M.
    Huntsman, D. G.
    Iacocca, M.
    Imielinski, M.
    Kalloger, S.
    Karlan, B. Y.
    Levine, D. A.
    Mills, G. B.
    Morrison, C.
    Mutch, D.
    Olvera, N.
    Orsulic, S.
    Park, K.
    Petrelli, N.
    Rabeno, B.
    Rader, J. S.
    Sikic, B. I.
    Smith-McCune, K.
    Sood, A. K.
    Bowtell, D.
    Penny, R.
    Testa, J. R.
    Chang, K.
    Dinh, H. H.
    Drummond, J. A.
    Fowler, G.
    Gunaratne, P.
    Hawes, A. C.
    Kovar, C. L.
    Lewis, L. R.
    Morgan, M. B.
    Newsham, I. F.
    Santibanez, J.
    Reid, J. G.
    Trevino, L. R.
    Wu, Y. -Q.
    Wang, M.
    [J]. NATURE, 2011, 474 (7353) : 609 - 615
  • [6] A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer
    Bonome, Tomas
    Levine, Douglas A.
    Shih, Joanna
    Randonovich, Mike
    Pise-Masison, Cindy A.
    Bogomolniy, Faina
    Ozbun, Laurent
    Brady, John
    Barrett, J. Carl
    Boyd, Jeff
    Birrer, Michael J.
    [J]. CANCER RESEARCH, 2008, 68 (13) : 5478 - 5486
  • [7] microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer
    Braconi, C.
    Kogure, T.
    Valeri, N.
    Huang, N.
    Nuovo, G.
    Costinean, S.
    Negrini, M.
    Miotto, E.
    Croce, C. M.
    Patel, T.
    [J]. ONCOGENE, 2011, 30 (47) : 4750 - 4756
  • [8] Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses
    Cabili, Moran N.
    Trapnell, Cole
    Goff, Loyal
    Koziol, Magdalena
    Tazon-Vega, Barbara
    Regev, Aviv
    Rinn, John L.
    [J]. GENES & DEVELOPMENT, 2011, 25 (18) : 1915 - 1927
  • [9] The functional role of long non-coding RNAs and epigenetics
    Cao, Jinneng
    [J]. BIOLOGICAL PROCEDURES ONLINE, 2014, 16
  • [10] Long noncoding RNAs and the genetics of cancer
    Cheetham, S. W.
    Gruhl, F.
    Mattick, J. S.
    Dinger, M. E.
    [J]. BRITISH JOURNAL OF CANCER, 2013, 108 (12) : 2419 - 2425