Abstract
The aim of the present study was to determine the expression profile of microRNA 638 (miR-638) and sex-determining region Y-box 2 (SOX2) in hepatocellular carcinoma (HCC), and to investigate their association with clinicopathological features and survival. Reverse transcription-quantitative polymerase chain reaction analysis was used to investigate miR-638 and SOX2 expression in 78 patients with HCC. Western blot and immunohistochemical analyses were performed in order to determine SOX2 protein expression in HCC samples. Combined with the clinical postoperative follow-up data, the expression of miR-638 and SOX2 and the association between this and the prognostic values of patients with HCC were statistically analyzed. The results of the present study confirmed that miR-638 expression in tumor tissues was significantly downregulated (P<0.001), while SOX2 expression was significantly increased, compared with healthy control tissues (P<0.05). In addition, a significant inverse correlation between miR-638 and SOX2 expression was also observed in the HCC tissues (r=-0.675; P<0.05). Clinicopathological correlation analysis demonstrated that reduced miR-638 and elevated SOX2 expression was significantly associated with the Tumor-Node-Metastasis stage and portal vascular invasion (P<0.05). However, no significant differences were observed in other clinicopathological features, including age, sex, tumor size, tumor differentiation and hepatitis status (P>0.05). Notably, follow-up analysis revealed that patients with HCC with low miR-638 expression and high SOX2 expression tended to have a significantly shorter postoperative survival time (P<0.001). It was concluded that miR-638 may serve a vital role in the occurrence and progression of HCC by regulating SOX2 expression and thus, that miR-638 and SOX2 may be critical as novel diagnostic and prognostic biomarkers for HCC.
Highlights
Hepatocellular carcinoma (HCC) has one of the highest cancer‐associated mortality rates worldwide, with a higher incidence observed more frequently in males than females [1]
In order to statistically analyze the correlation between microRNA 638 (miR‐638) and sex‐determining region Y‐box 2 (SOX2), a cross analysis was performed and is presented in Table III (χ2=15.551; P
The data indicated that miR‐638 may negatively regulate SOX2 expression, and may be associated with advanced TNM stages and portal vascular invasion
Summary
Hepatocellular carcinoma (HCC) has one of the highest cancer‐associated mortality rates worldwide, with a higher incidence observed more frequently in males than females [1]. MiR‐638 has been demonstrated to be involved in colorectal carcinoma [14], gastric cancer [15], breast cancer [16] and osteosarcoma [17], YE et al: EXPRESSION AND CLINICAL SIGNIFICANCE OF miR-638 AND SOX2 IN HCC through dysregulation of its target genes as a tumor suppressor. MiR‐638 has been demonstrated to promote melanoma progression and metastasis by suppressing tumor protein p53‐mediated apoptosis pathways and autophagy as an oncogene [18]. These inconsistent observations suggested that the function of miR‐638 in tumorigenesis is cancer‐specific
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