Abstract
BackgroundBoth microRNA (miR)-196a and miR-196b are implicated in normal cell differentiation, proliferation, and in tumorigenesis of various cancer types. Especially, miR-196a exerts a pro-oncogenic influence in colorectal cancer (CRC) cells and miR-196b expression is upregulated in CRC tissues. The aim of this study was to evaluate the associations of miR-196a and miR-196b dysregulation with clinicopathological characteristics and prognosis in patients with CRC.MethodsQuantitative real time-PCR (qRT-PCR) was performed to detect the expression levels of miR-196a and miR-196b in 126 pairs of fresh tumor samples matched with adjacent colorectal mucosa obtained from 126 patients with CRC.ResultsmiR-196a and miR-196b expression levels in CRC tissues were significantly higher than those in adjacent colorectal mucosa (both P < 0.002). Interestingly, the expression levels of miR-196a in CRC tissues were positively correlated with those of miR-196b. Then, high miR-196a expression and high miR-196b expression, alone or in combination, were all statistically linked to the presence of lymph node metastasis, the poor differentiation grade, and the advanced TNM stage of CRC. Moreover, overall and disease-free survivals of CRC patients with high miR-196a expression, high miR-196b expression and miR-196a-high/miR-196b-high expression tended to be shorter than the corresponding control groups (log-rank statistic, all P < 0.001). Furthermore, multivariate analysis indicated miR-196a and/or miR-196b expression as independent prognostic indicators for CRC patients (all P < 0.05).ConclusionsBoth miR-196a and miR-196b may be correlated with aggressive progression and unfavorable clinical outcome in CRC patients. Combined expression of miR-196a and miR-196b may be a promising biomarker in identifying a poor prognosis group of CRC.
Highlights
Both microRNA-196a and miR-196b are implicated in normal cell differentiation, proliferation, and in tumorigenesis of various cancer types
Upregulation of miR-196a and miR-196b in human colorectal cancer (CRC) tissues miR-196a (Cancer vs. Normal: 4.21 ± 1.66 vs. 2.06 ± 1.01, P < 0.001, Figure 1A) and miR-196b (Cancer vs. Normal: 4.38 ± 1.81 vs. 2.11 ± 1.02, P < 0.001, Figure 1B) expression were found significantly upregulated in CRC compared to adjacent colorectal mucosa
High miR-196a expression and high miR-196b expression were both significantly associated with the presence of lymph node metastasis, poor differentiation grade and advanced TNM stage
Summary
Both microRNA (miR)-196a and miR-196b are implicated in normal cell differentiation, proliferation, and in tumorigenesis of various cancer types. The aim of this study was to evaluate the associations of miR-196a and miR-196b dysregulation with clinicopathological characteristics and prognosis in patients with CRC. The 5-year overall survival rate of CRC patients has been reported to be as high as 71.3%, the survival rate in patients with recurrence is only 40% [3]. The recurrence rate of CRC patients who received curative resection has been reported to be 27.3% [5]. There has been no breakthrough in the control of CRC once it develops extra lymph node metastasis. Several clinicopathological characteristics, such as tumor size, TNM stage, differentiation grade, lymph node metastasis and tumor invasion, have been reported to evaluate CRC patients’ prognosis, it still varies greatly among patients with the same clinicopathological characteristics [6]. It is extremely necessary to screen novel and efficient biomarkers which can be used to predict recurrence in order to choose more appropriate treatment for each CRC patients
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