Expression of a set of small nucleolar RNAs (snoRNAs) was found to be significantly elevated in cancer tissue, compared with normal tissue, and expression of a specific snoRNA, SNORA42, was associated with poor overall and disease-free survival in patients with colorectal cancer (CRC).
Elevated expression of the specific snoRNA SNORA42 was an independent prognostic indicator for overall survival (hazard ratio, 2.11; P = .021), disease-free survival (HR, 3.17; P = .011), and distant metastasis (HR, 2.66; P .023). In a subset of patients with stage II CRC, the significant association between high expression of SNORA42 and poor prognosis remained.
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The majority of patients with stage II CRC are cured by surgery alone, but a significant proportion experience disease progression. According to Dr. Yoshinaga Okugawa of the Center for Gastrointestinal Cancer Research at the Baylor University Medical Center, Dallas, and colleagues, adjuvant chemotherapy treatment for all patients with stage II cancer is controversial.
“Therefore, identification of such high-risk patients with CRC using molecular biomarkers such as SNORA42 expression will allow use of adjuvant chemotherapy after surgery only in a select subgroup of high-risk patients to improve their prognosis,” they wrote (Gut 2015 Oct 15. doi: 10.1136/gutjnl-2015.309359).
The research examined expression levels of RNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue samples from 250 patients with colorectal cancer and 24 matched controls. The initial focus was on four snoRNAs that were reported to be dysregulated in other cancers. The study found that all four of the snoRNAs were significantly upregulated in CRC tissue, compared with normal tissue. Receiver operating characteristic (ROC) curves showed that expression levels of all four snoRNAs distinguished between cancer and noncancer tissue; area under the ROC curves values ranged from 0.75 to 0.88.
SnoRNAs are single-stranded, noncoding RNAs that have recently emerged as important components in the control of cell fate and oncogenesis in various cancers. In addition, studies have suggested the potential of snoRNAs as prognostic indicators.
While the expression levels of all four snoRNAs distinguished cancer tissue from normal tissue, only one of the snoRNAs, SNORA42, had expression levels that correlated with disease outcomes (overall survival, disease-free survival, and distant metastasis).
To characterize the biologic role of SNORN42 in CRC progression, the research team investigated its expression and impact on cancer cell lines and animal models. Overexpressed SNORN42 enhanced cell proliferation and tumorigenicity in cultured cells and in an animal model of CRC.
Taken together, the results suggest potential clinical usefulness of SNORA42 as a diagnostic and predictive biomarker in patients with CRC.
Dr. Okugawa and coauthors reported having no disclosures.