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.
- COLORECTAL CANCER
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Contributors Study concept and design, analysis and interpretation of data and statistical analysis: YO and AG; provision of samples: YT, TN, KT, YI and MK; acquisition of data: YO, ST, HM and AG; drafting of the manuscript: YO, ST, CRB and AG.
Funding This work was supported by grants R01 CA72851, CA181572 and U01 CA187956 from the National Cancer Institute, National Institutes of Health, a pilot grant from Charles A Sammons Cancer Center, and funds from the Baylor Research Institute to AG. YO was supported in part by a Grant in Aid for Scientific Research from Takeda science foundation, Japan.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Institutional review boards of all participating institutions.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All data are contained within the article.