Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer.
Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer.
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DOI：
10.1136/gutjnl-2015-309359
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发表时间：
2017-01
期刊：
影响因子：
24.5
通讯作者：
Goel A
中科院分区：
文献类型：
--
作者：
Okugawa Y;Toiyama Y;Toden S;Mitoma H;Nagasaka T;Tanaka K;Inoue Y;Kusunoki M;Boland CR;Goel A
尽管近年来结直肠癌（CRC）的治疗取得了进展，但CRC患者的预后仍然不理想，治疗性手术后的转移复发是导致预后不良的主要原因。因此，鉴别预后标志物来预测结直肠癌的临床预后是十分必要的。最近的证据揭示了小核仁rna （snoRNAs）在肿瘤发生中的新作用。在此，我们系统地评估了snoRNAs在结直肠癌中的失调，并阐明了snoRNAs在结直肠癌中的生物标志物潜力和生物学意义。我们分析了来自三个独立队列和6个结直肠癌细胞系的274个结直肠组织中4种snorna的表达水平。通过一系列体外和体内实验研究SNORA42在CRC中作用的功能表征。在筛选阶段，四种snorna在结直肠癌组织中的表达水平均显著高于相应的正常粘膜。在临床验证队列中，SNORA42表达增加是总生存期和无病生存期的独立预后因素，也是远处转移的独立危险因素。在另一个独立队列中，SNORA42的表达与总生存率呈负相关，并确定了II期CRC复发风险高、预后差的患者。此外，体外和体内分析表明，SNORA42过表达可增强细胞增殖、迁移、侵袭、抗瘤性和致瘤性。SNORA42是一种新的癌基因，可作为预测结直肠癌患者复发和预后的生物标志物。
Despite recent advances in colorectal cancer (CRC) treatment, the prognosis of CRC patients still remains substandard, and metastatic recurrence following curative surgery is the leading cause of poor prognosis. Therefore, it is imperative to identify prognostic markers to predict the clinical outcome of CRC. Recent evidence revealed the new role of small nucleolar RNAs (snoRNAs) in oncogenesis. Herein, we systematically evaluated dysregulation of snoRNAs in CRC, and clarified the biomarker potential and biological significance of snoRNAs in CRC. We analyzed expression levels of four snoRNAs in 274 colorectal tissues from three independent cohorts, and 6 CRC cell lines. The functional characterization for the role of SNORA42 in CRC was investigated through a series of in vitro and in vivo experiments. 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 an independent 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 analysis showed that SNORA42 overexpression resulted in enhanced cell proliferation, migration, invasion, anoikis resistance, and tumorigenicity. SNORA42 appears to a novel oncogene and could serve as a promising predictive biomarker for recurrence and prognosis in CRC patients.