NF-YA Overexpression in Lung Cancer: LUAD

被引:31
作者
Bezzecchi, Eugenia [1 ]
Ronzio, Mirko [1 ]
Semeghini, Valentina [1 ]
Andrioletti, Valentina [2 ]
Mantovani, Roberto [1 ]
Dolfini, Diletta [1 ]
机构
[1] Univ Milan, Dipartimento Biosci, Via Celoria 26, I-20133 Milan, Italy
[2] Univ Hosp Tubingen, Internal Med 8, Otfried Muller Str 14, D-72076 Tubingen, Germany
关键词
lung cancer; LUAD; transcription factors; TCGA; CCAAT box; NF-YA; alternative splicings; EXPRESSION; ACTIVATION; DISCOVERY; SEQUENCES; ELEMENTS; SUBTYPES; GENES; SET;
D O I
10.3390/genes11020198
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The trimeric transcription factor (TF) NF-Y regulates the CCAAT box, a DNA element enriched in promoters of genes overexpressed in many types of cancer. The regulatory NF-YA is present in two major isoforms, NF-YAl ("long") and NF-YAs ("short"). There is growing indication that NF-YA levels are increased in tumors. Here, we report interrogation of RNA-Seq TCGA (The Cancer Genome Atlas)-all 576 samples-and GEO (Gene Expression Ominibus) datasets of lung adenocarcinoma (LUAD). NF-YAs is overexpressed in the three subtypes, proliferative, inflammatory, and TRU (terminal respiratory unit). CCAAT is enriched in promoters of tumor differently expressed genes (DEG) and in the proliferative/inflammatory intersection, matching with KEGG (Kyoto Encyclopedia of Genes and Genomes) terms cell-cycle and signaling. Increasing levels of NF-YAs are observed from low to high CpG island methylator phenotypes (CIMP). We identified 166 genes overexpressed in LUAD cell lines with low NF-YAs/NF-YAl ratios: applying this centroid to TCGA samples faithfully predicted tumors' isoform ratio. This signature lacks CCAAT in promoters. Finally, progression-free intervals and hazard ratios concurred with the worst prognosis of patients with either a low or high NF-YAs/NF-YAl ratio. In conclusion, global overexpression of NF-YAs is documented in LUAD and is associated with aggressive tumor behavior; however, a similar prognosis is recorded in tumors with high levels of NF-YAl and overexpressed CCAAT-less genes.
引用
收藏
页数:17
相关论文
共 40 条
[1]   Contextual Refinement of Regulatory Targets Reveals Effects on Breast Cancer Prognosis of the Regulome [J].
Andrews, Erik ;
Wang, Yue ;
Xia, Tian ;
Cheng, Wenqing ;
Cheng, Chao .
PLOS COMPUTATIONAL BIOLOGY, 2017, 13 (01)
[2]  
[Anonymous], 2015, R TOP DOC
[3]   NF-YA Overexpression in Lung Cancer: LUSC [J].
Bezzecchi, Eugenia ;
Ronzio, Mirko ;
Dolfini, Diletta ;
Mantovani, Roberto .
GENES, 2019, 10 (11)
[4]  
Bie Liang-Yu, 2019, Chronic Dis Transl Med, V5, P44, DOI 10.1016/j.cdtm.2018.07.003
[5]  
Borcherding Nicholas, 2018, F1000Res, V7, P1235, DOI 10.12688/f1000research.15789.1
[6]   Gene regulatory network construction identified NFYA as a diffuse subtype-specific prognostic factor in gastric cancer [J].
Cao, Bin ;
Zhao, Yu ;
Zhang, Zheng ;
Li, Hengcun ;
Xing, Jie ;
Guo, Shuilong ;
Qiu, Xintao ;
Zhang, Shutian ;
Min, Li ;
Zhu, Shengtao .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2018, 53 (05) :1857-1868
[7]   NF-YC Complexity Is Generated by Dual Promoters and Alternative Splicing [J].
Ceribelli, Michele ;
Benatti, Paolo ;
Imbriano, Carol ;
Mantovani, Roberto .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (49) :34189-34200
[8]   Non-small-cell lung cancers: a heterogeneous set of diseases [J].
Chen, Zhao ;
Fillmore, Christine M. ;
Hammerman, Peter S. ;
Kim, Carla F. ;
Wong, Kwok-Kin .
NATURE REVIEWS CANCER, 2014, 14 (08) :535-546
[9]   Prognostic role of NF-YA splicing isoforms and Lamin A status in low grade endometrial cancer [J].
Cicchillitti, Lucia ;
Corrado, Giacomo ;
Carosi, Mariantonia ;
Dabrowska, Malgorzata Ewa ;
Loria, Rossella ;
Falcioni, Rita ;
Cutillo, Giuseppe ;
Piaggio, Giulia ;
Vizza, Enrico .
ONCOTARGET, 2017, 8 (05) :7935-7945
[10]   Comprehensive molecular profiling of lung adenocarcinoma [J].
Collisson, Eric A. ;
Campbell, Joshua D. ;
Brooks, Angela N. ;
Berger, Alice H. ;
Lee, William ;
Chmielecki, Juliann ;
Beer, David G. ;
Cope, Leslie ;
Creighton, Chad J. ;
Danilova, Ludmila ;
Ding, Li ;
Getz, Gad ;
Hammerman, Peter S. ;
Hayes, D. Neil ;
Hernandez, Bryan ;
Herman, James G. ;
Heymach, John V. ;
Jurisica, Igor ;
Kucherlapati, Raju ;
Kwiatkowski, David ;
Ladanyi, Marc ;
Robertson, Gordon ;
Schultz, Nikolaus ;
Shen, Ronglai ;
Sinha, Rileen ;
Sougnez, Carrie ;
Tsao, Ming-Sound ;
Travis, William D. ;
Weinstein, John N. ;
Wigle, Dennis A. ;
Wilkerson, Matthew D. ;
Chu, Andy ;
Cherniack, Andrew D. ;
Hadjipanayis, Angela ;
Rosenberg, Mara ;
Weisenberger, Daniel J. ;
Laird, Peter W. ;
Radenbaugh, Amie ;
Ma, Singer ;
Stuart, Joshua M. ;
Byers, Lauren Averett ;
Baylin, Stephen B. ;
Govindan, Ramaswamy ;
Meyerson, Matthew ;
Rosenberg, Mara ;
Gabriel, Stacey B. ;
Cibulskis, Kristian ;
Sougnez, Carrie ;
Kim, Jaegil ;
Stewart, Chip .
NATURE, 2014, 511 (7511) :543-550