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The Clinical Significance of MiR-429 as a Predictive Biomarker in Colorectal Cancer Patients Receiving 5-Fluorouracil Treatment

View Article: PubMed Central - PubMed

ABSTRACT

Background: 5-Fluorouracil (5-FU) based treatment is the standard therapy for metastatic colorectal cancer (CRC), but the development of chemoresistance is inevitable. Increasing evidence shows that dysregulation of microRNAs (miRNAs) is involved in malignant transformation. Thus, it is imperative that we find new diagnostic and prognostic marker for chemotherapy in CRC.

Material/methods: For clinical parameter analysis, 78 CRC tissues and adjacent normal tissues and 45 serum specimens from CRC patients were included in this study. For chemo-response analysis, 116 primary tissues were collected from the patients receiving first-line 5-FU treatment. Quantitative Real-Time PCR (qRT-PCR) was used to detect microRNAs expression.

Results: The expression of miR-429 was significantly increased in both serum and primary tissues from CRC patients, and enhanced miR-429 level was associated with tumor size, lymph node metastasis, and TNM stage. The diagnostic and prognostic values were also confirmed in CRC by using primary tissues. For patients receiving 5-FU-based treatment, miR-429 levels were significantly lower in responding group. The proportions of patients that did not experience response to therapy were higher in primary tumors with high miR-429 expression levels as compared with primary tumors with low miR-429 expression levels. Finally, Kaplan-Meier survival analysis showed that miR-429 is an independent prognostic indicator for chemo-response to 5-FU therapy among CRC patients.

Conclusions: High level of miR-429 expression was correlated with enhanced malignant potential and poor prognosis of CRC patients. Furthermore, miR-429 could affect the chemo-sensitivity of CRC patients to 5-FU therapy and was associated with poor response to 5-FU-based chemotherapy in patients with CRC.

No MeSH data available.


MiR-429 is a prognostic factor in patients receiving 5-FU-based treatment. (A) The proportion of CRC patients not responding to 5-FU-based chemotherapy was significantly higher in the high miR-429 expressing group than in the low group. (B) Patients with high miR-429 expression were associated with short overall survival among CRC patients receiving 5-FU-based therapy.
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f4-medscimonit-22-3352: MiR-429 is a prognostic factor in patients receiving 5-FU-based treatment. (A) The proportion of CRC patients not responding to 5-FU-based chemotherapy was significantly higher in the high miR-429 expressing group than in the low group. (B) Patients with high miR-429 expression were associated with short overall survival among CRC patients receiving 5-FU-based therapy.

Mentions: Finally, we aimed to explore the prognostic value of miR-429 for chemotherapy. When we stratified patients into a low (n=46) and a high (n=70) groups with the previously established optimal cut-off value of relative miR-429 level (3.08), the proportion of patients not responding to chemotherapy was significantly higher in the high miR-429 expressing group than in the low group (p<0.01, Figure 4A). The 5-year survival rate of the CRC patients whose tumors expressed high levels of miR-429 was 21.4% (15/70), which was significantly lower than that of the patients whose tumors expressed low levels of miR-429 (52.2%, 24/46); this difference was statistically significant (p=0.0011). Besides, the Kaplan-Meier survival analysis also showed that patients with a low level of miR-429 expression had a significant longer overall survival than did those with a high level of miR-429 expression (p=0.0001, Figure 4B). Furthermore, we performed Cox regression multivariate analysis to identify whether miR-429 was an independent indicator for overall survival of CRC patients who received 5-FU chemotherapy. As expected, a high miR-429 level was significantly correlated with poorer survival in an independent manner (Table 3). Taken together, these results indicated that miR-429 was an independent predictor for chemo-response to 5-FU-based treatment in CRC patients.


The Clinical Significance of MiR-429 as a Predictive Biomarker in Colorectal Cancer Patients Receiving 5-Fluorouracil Treatment
MiR-429 is a prognostic factor in patients receiving 5-FU-based treatment. (A) The proportion of CRC patients not responding to 5-FU-based chemotherapy was significantly higher in the high miR-429 expressing group than in the low group. (B) Patients with high miR-429 expression were associated with short overall survival among CRC patients receiving 5-FU-based therapy.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036382&req=5

f4-medscimonit-22-3352: MiR-429 is a prognostic factor in patients receiving 5-FU-based treatment. (A) The proportion of CRC patients not responding to 5-FU-based chemotherapy was significantly higher in the high miR-429 expressing group than in the low group. (B) Patients with high miR-429 expression were associated with short overall survival among CRC patients receiving 5-FU-based therapy.
Mentions: Finally, we aimed to explore the prognostic value of miR-429 for chemotherapy. When we stratified patients into a low (n=46) and a high (n=70) groups with the previously established optimal cut-off value of relative miR-429 level (3.08), the proportion of patients not responding to chemotherapy was significantly higher in the high miR-429 expressing group than in the low group (p<0.01, Figure 4A). The 5-year survival rate of the CRC patients whose tumors expressed high levels of miR-429 was 21.4% (15/70), which was significantly lower than that of the patients whose tumors expressed low levels of miR-429 (52.2%, 24/46); this difference was statistically significant (p=0.0011). Besides, the Kaplan-Meier survival analysis also showed that patients with a low level of miR-429 expression had a significant longer overall survival than did those with a high level of miR-429 expression (p=0.0001, Figure 4B). Furthermore, we performed Cox regression multivariate analysis to identify whether miR-429 was an independent indicator for overall survival of CRC patients who received 5-FU chemotherapy. As expected, a high miR-429 level was significantly correlated with poorer survival in an independent manner (Table 3). Taken together, these results indicated that miR-429 was an independent predictor for chemo-response to 5-FU-based treatment in CRC patients.

View Article: PubMed Central - PubMed

ABSTRACT

Background: 5-Fluorouracil (5-FU) based treatment is the standard therapy for metastatic colorectal cancer (CRC), but the development of chemoresistance is inevitable. Increasing evidence shows that dysregulation of microRNAs (miRNAs) is involved in malignant transformation. Thus, it is imperative that we find new diagnostic and prognostic marker for chemotherapy in CRC.

Material/methods: For clinical parameter analysis, 78 CRC tissues and adjacent normal tissues and 45 serum specimens from CRC patients were included in this study. For chemo-response analysis, 116 primary tissues were collected from the patients receiving first-line 5-FU treatment. Quantitative Real-Time PCR (qRT-PCR) was used to detect microRNAs expression.

Results: The expression of miR-429 was significantly increased in both serum and primary tissues from CRC patients, and enhanced miR-429 level was associated with tumor size, lymph node metastasis, and TNM stage. The diagnostic and prognostic values were also confirmed in CRC by using primary tissues. For patients receiving 5-FU-based treatment, miR-429 levels were significantly lower in responding group. The proportions of patients that did not experience response to therapy were higher in primary tumors with high miR-429 expression levels as compared with primary tumors with low miR-429 expression levels. Finally, Kaplan-Meier survival analysis showed that miR-429 is an independent prognostic indicator for chemo-response to 5-FU therapy among CRC patients.

Conclusions: High level of miR-429 expression was correlated with enhanced malignant potential and poor prognosis of CRC patients. Furthermore, miR-429 could affect the chemo-sensitivity of CRC patients to 5-FU therapy and was associated with poor response to 5-FU-based chemotherapy in patients with CRC.

No MeSH data available.