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

Yoshinaga Okugawa, Yuji Toiyama, Shusuke Toden, Hiroki Mitoma, Takeshi Nagasaka, Koji Tanaka, Yasuhiro Inoue, Masato Kusunoki, C. Richard Boland, Ajay Goel

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)107-117
Number of pages11
JournalGut
Volume66
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

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Oncogenes
Colorectal Neoplasms
Biomarkers
Small Nucleolar RNA
Recurrence
Anoikis
Survival
Colonic Neoplasms
Disease-Free Survival
Cell Movement
Carcinogenesis
Mucous Membrane
Cell Proliferation
Neoplasm Metastasis
Cell Line
Mortality
Neoplasms

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Okugawa, Y., Toiyama, Y., Toden, S., Mitoma, H., Nagasaka, T., Tanaka, K., ... Goel, A. (2017). Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer. Gut, 66(1), 107-117. https://doi.org/10.1136/gutjnl-2015-309359

Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer. / Okugawa, Yoshinaga; Toiyama, Yuji; Toden, Shusuke; Mitoma, Hiroki; Nagasaka, Takeshi; Tanaka, Koji; Inoue, Yasuhiro; Kusunoki, Masato; Boland, C. Richard; Goel, Ajay.

In: Gut, Vol. 66, No. 1, 01.01.2017, p. 107-117.

Research output: Contribution to journalArticle

Okugawa, Y, Toiyama, Y, Toden, S, Mitoma, H, Nagasaka, T, Tanaka, K, Inoue, Y, Kusunoki, M, Boland, CR & Goel, A 2017, 'Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer', Gut, vol. 66, no. 1, pp. 107-117. https://doi.org/10.1136/gutjnl-2015-309359
Okugawa, Yoshinaga ; Toiyama, Yuji ; Toden, Shusuke ; Mitoma, Hiroki ; Nagasaka, Takeshi ; Tanaka, Koji ; Inoue, Yasuhiro ; Kusunoki, Masato ; Boland, C. Richard ; Goel, Ajay. / Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer. In: Gut. 2017 ; Vol. 66, No. 1. pp. 107-117.
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AU - Toden, Shusuke

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AU - Tanaka, Koji

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N2 - 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.

AB - 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.

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