Downregulation of miR-193a-5p correlates with lymph node metastasis and poor prognosis in colorectal cancer

Abstract

Aim: To investigate the correlation of miR-193a-5p with lymph node metastasis and postoperative survival of colorectal cancer (CRC) patients.

Methods: A total of 304 formalin-fixed, paraffin-embedded specimens (69 paired cancer and normal tissues, 55 primary tumors of stage III CRC and matched lymph nodes, and 56 primary tumors of stage II CRC) were included in this study. The relative expression levels of miR-193a-5p in the normal mucosa, primary cancer, and metastatic lymph node lesions were measured by quantitative real-time reverse transcriptase polymerase chain reaction. We evaluated the association of its expression with colorectal cancer lymph node metastasis, clinicopathological factors, and patient survival.

Results: The relative expression level of miR-193a-5p was significantly lower in CRC tissues than in the normal mucosa (P = 0.0060). The expression levels of miR-193a-5p were lower in primary CRC tissues with lymph node metastases than in those without metastases (P = 0.0006), and decreased expression of miR-193a-5p correlated with advanced lymph node metastatic stage (P = 0.0007). Kaplan-Meier analysis showed that patients with low miR-193a-5p expression had decreased disease-free survival (DFS) (P = 0.0026) and poor overall survival (OS) (P = 0.0003). Interestingly, for the group of patients with lymph node metastases, miR-193a-5p expression was also related to survival. Patients with low miR-193a-5p expression had decreased DFS (P = 0.0262) and poor OS (P = 0.0230). Moreover, multivariate analysis indicated that downregulation of miR-193a-5p was an independent predictor of poor OS.

Conclusion: Downregulation of miR-193a-5p correlates with lymph node metastasis and poor survival of CRC. miR-193a-5p may be a useful biomarker for CRC diagnosis, metastasis and prognosis prediction.

Keywords: Biomarker; Colorectal cancer; Lymph node metastasis; Prognosis; miR-193a-5p.

Figure 1

Expression level of miR-193a-5p in colorectal cancer, metastatic lymph node and normal tissues. A: Comparison of miR-193a-5p expression between colorectal cancer and normal mucosa in 69 paired samples. miR-193a-5p expression levels were higher in normal tissues than in cancer tissues (P = 0.0060); B: Comparison of miR-193a-5p expression in primary colorectal cancer (CRC) tissue with and without lymph node metastasis. miR-193a-5p expression levels were significantly lower in primary CRC with lymph node metastasis than without lymph node metastasis (P = 0.0006); C: Correlation of miR-193a-5p expression in primary CRC with lymph node stage (N0/N1/N2). Decreased expression of miR-193a-5p was associated with advanced lymph node stage (P = 0.0007); D: Association of miR-193a-5p expression in colorectal cancer with paired metastatic lymph nodes. No significant difference of miR-193a-5p expression was observed between colorectal cancer and paired metastatic lymph nodes (P = 0.9321). N: Lymph node stage; N0: Stage N0; N1: Stage N1; N2: Stage N2.

Figure 2

Kaplan-Meier survival curves of patients with colorectal cancer based on miR-193a-5p expression. A: Kaplan-Meier disease free survival curves of patients with colorectal cancer (CRC) based on miR-193a-5p expression. Patients in the low expression group had significantly lower disease free survival rates than those in the high expression group (log-rank test, P = 0.0026); B: Kaplan-Meier overall survival curves of patients with CRC based on miR-193a-5p expression. Patients in the low expression group had significantly lower overall survival rates than those in the high expression group (log-rank test, P = 0.0003); C: Kaplan-Meier disease free survival curves of patients with lymph node metastases based on miR-193a-5p expression. Patients in the low expression group had significantly lower disease free survival rates than those in high expression group (log-rank test, P = 0.0262); D: Kaplan-Meier overall survival curves of patients with lymph node metastases based on miR-193a-5p expression. Patients in the low expression group had significantly lower overall survival rates than those in high expression group (log-rank test, P = 0.0230). N: Lymph node stage; N0: Stage N0; N1: Stage N1; N2: Stage N2.