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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 expression was associated with chemo-response to 5-FU-based treatment in CRC patients. (A) MiR-429 levels were significantly higher in non-responding group than in responding group among CRC patients receiving 5-FU-based chemotherapy. (B) No significant difference was found of miR-429 level among different 5-FU-based chemotherapy methods. (C) ROC curve was drawn to explore the capacity of miR-429 in distinguishing responding and non-responding patients receiving 5-FU-based treatment.
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f3-medscimonit-22-3352: MiR-429 expression was associated with chemo-response to 5-FU-based treatment in CRC patients. (A) MiR-429 levels were significantly higher in non-responding group than in responding group among CRC patients receiving 5-FU-based chemotherapy. (B) No significant difference was found of miR-429 level among different 5-FU-based chemotherapy methods. (C) ROC curve was drawn to explore the capacity of miR-429 in distinguishing responding and non-responding patients receiving 5-FU-based treatment.

Mentions: We next sought to validate the association between miR-429 and response to treatment in 116 primary tissues. Patients were divided into responding (CR+PR) and non-responding (SD+PD) groups according to RECIST criteria. The expression level of miR-429 was significantly higher in patients who did not respond to treatment (n=42) compared with patients responding to treatment (n=74) (p<0.001, Figure 3A). To exclude the influence from different chemotherapy methods, miR-429 expression was determined in patients receiving different 5-FU-based regimens, and the results showed that no difference was found between different regimens, including FOLFOX (5-FU+oxaliplatin+leucovorin); FOLFIRI (5-FU+leucovorin+irinotecan) and 5-FU/Lv (5-FU+leucovorin) (p=0.1191, Figure 3B). Then, a receiver operating characteristic (ROC) curve analysis was performed to investigate the potential significance in predicting the patients’ response to chemotherapy. The area under the curve of miR-429 were 0.721 (95% CI: 0.630–0.800, Figure 3C), and the diagnostic sensitivity and specificity reached 52.70% and 85.71%, respectively. These results indicated that miR-429 was associated with 5-FU-based chemo-response among CRC patients.


The Clinical Significance of MiR-429 as a Predictive Biomarker in Colorectal Cancer Patients Receiving 5-Fluorouracil Treatment
MiR-429 expression was associated with chemo-response to 5-FU-based treatment in CRC patients. (A) MiR-429 levels were significantly higher in non-responding group than in responding group among CRC patients receiving 5-FU-based chemotherapy. (B) No significant difference was found of miR-429 level among different 5-FU-based chemotherapy methods. (C) ROC curve was drawn to explore the capacity of miR-429 in distinguishing responding and non-responding patients receiving 5-FU-based treatment.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036382&req=5

f3-medscimonit-22-3352: MiR-429 expression was associated with chemo-response to 5-FU-based treatment in CRC patients. (A) MiR-429 levels were significantly higher in non-responding group than in responding group among CRC patients receiving 5-FU-based chemotherapy. (B) No significant difference was found of miR-429 level among different 5-FU-based chemotherapy methods. (C) ROC curve was drawn to explore the capacity of miR-429 in distinguishing responding and non-responding patients receiving 5-FU-based treatment.
Mentions: We next sought to validate the association between miR-429 and response to treatment in 116 primary tissues. Patients were divided into responding (CR+PR) and non-responding (SD+PD) groups according to RECIST criteria. The expression level of miR-429 was significantly higher in patients who did not respond to treatment (n=42) compared with patients responding to treatment (n=74) (p<0.001, Figure 3A). To exclude the influence from different chemotherapy methods, miR-429 expression was determined in patients receiving different 5-FU-based regimens, and the results showed that no difference was found between different regimens, including FOLFOX (5-FU+oxaliplatin+leucovorin); FOLFIRI (5-FU+leucovorin+irinotecan) and 5-FU/Lv (5-FU+leucovorin) (p=0.1191, Figure 3B). Then, a receiver operating characteristic (ROC) curve analysis was performed to investigate the potential significance in predicting the patients’ response to chemotherapy. The area under the curve of miR-429 were 0.721 (95% CI: 0.630–0.800, Figure 3C), and the diagnostic sensitivity and specificity reached 52.70% and 85.71%, respectively. These results indicated that miR-429 was associated with 5-FU-based chemo-response among 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.