Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer

被引:116
|
作者
Okugawa, Yoshinaga [1 ,2 ,3 ]
Toiyama, Yuji [1 ,2 ,3 ,4 ]
Toden, Shusuke [1 ,2 ,3 ]
Mitoma, Hiroki [5 ]
Nagasaka, Takeshi [6 ]
Tanaka, Koji [4 ]
Inoue, Yasuhiro [4 ]
Kusunoki, Masato [4 ]
Boland, C. Richard [1 ,2 ,3 ]
Goel, Ajay [1 ,2 ,3 ]
机构
[1] Baylor Univ, Med Ctr, Ctr Gastrointestinal Canc Res, 3500 Gaston Ave,Suite H-250, Dallas, TX 75246 USA
[2] Baylor Univ, Med Ctr, Ctr Epigenet Canc Prevent & Canc Genom, Baylor Res Inst, 3500 Gaston Ave,Suite H-250, Dallas, TX 75246 USA
[3] Baylor Univ, Med Ctr, Charles A Sammons Canc Ctr, Dallas, TX USA
[4] Mie Univ, Grad Sch Med, Inst Life Sci, Dept Gastrointestinal & Pediat Surg,Div Reparat M, Tsu, Mie, Japan
[5] Baylor Hlth Care Syst, Baylor Res Inst, Baylor Inst Immunol Res, Dallas, TX USA
[6] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol Surg & Surg Oncol, Okayama, Japan
基金
美国国家卫生研究院;
关键词
NUCLEOLAR RNA SIGNATURES; ADJUVANT CHEMOTHERAPY; CELL-PROLIFERATION; POOR-PROGNOSIS; COLON-CANCER; SNORNA U50; EXPRESSION; APOPTOSIS; ANOIKIS; GENES;
D O I
10.1136/gutjnl-2015-309359
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Purpose Despite recent advances in colorectal cancer (CRC) treatment, the prognosis of patients suffering from this malignancy still remains substandard, and metastatic recurrence following curative surgery is the leading cause of mortality. Therefore, it is imperative to identify prognostic markers to predict the clinical outcome of CRC patients. Recent evidence revealed the new role of small nucleolar RNAs (snoRNAs) in oncogenesis. Herein, we systematically evaluated dysregulation of snoRNAs in CRC and clarified their biomarker potential and biological significance in CRC. Experimental design We analysed expression levels of 4 snoRNAs in 274 colorectal tissues from 3 independent cohorts and 6 colon cancer cell lines. The functional characterisation for the role of SNORA42 in CRC was investigated through a series of in vitro and in vivo experiments. Results In the screening phase, expression levels of all four snoRNAs were significantly elevated in CRC tissues than in corresponding normal mucosa. In the clinical validation cohort, increased SNORA42 expression was an independent prognostic factor for overall survival and disease-free survival, and was a risk factor for distant metastasis. SNORA42 expression negatively correlated with overall survival in an additional independent cohort and identified the patients with high risk for recurrence and poor prognosis in stage II CRC. Furthermore, in vitro and in vivo analyses showed that SNORA42 overexpression resulted in enhanced cell proliferation, migration, invasion, anoikis resistance and tumorigenicity. Conclusions SNORA42 appears to be a novel oncogene and could serve as a promising predictive biomarker for recurrence and prognosis in patients with CRC.
引用
收藏
页码:107 / 117
页数:11
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