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Stromal expression of miR-21 in T3-4a colorectal cancer is an independent predictor of early tumor relapse.

Kang WK, Lee JK, Oh ST, Lee SH, Jung CK - BMC Gastroenterol (2015)

Bottom Line: Patients with neoadjuvant therapy and distant metastasis at presentation were excluded.Immunohistochemistry was used to detect E-cadherin and metastasis-associated protein1 expression.Stage II colorectal cancer patients with high levels of miR-21 are at higher risk for tumor recurrence and should be considered for more intensive treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. wonkkang@catholic.ac.kr.

ABSTRACT

Background: MicroRNA-21 (miR-21) is an oncogenic microRNA that regulates the expression of multiple cancer-related target genes. miR-21 has been associated with progression of some types of cancer. Metastasis-associated protein1 expression and loss of E-cadherin expression are correlated with cancer progression and metastasis in many cancer types. In advanced colorectal cancer, the clinical significance of miR-21 expression remains unclear. We aimed to investigate the impact of miR-21 expression in advanced colorectal cancer and its correlation with target proteins associated with colorectal cancer progression.

Methods: From 2004 to 2007, 277 consecutive patients with T3-4a colorectal cancer treated with R0 surgical resection were included. Patients with neoadjuvant therapy and distant metastasis at presentation were excluded. The expression of miR-21 was investigated by in situ hybridization. Immunohistochemistry was used to detect E-cadherin and metastasis-associated protein1 expression.

Results: High stromal expression of miR-21 was found in 76 of 277 (27.4%) colorectal cancer samples and was correlated with low E-cadherin expression (P = 0.019) and high metastasis-associated protein1 expression (P = 0.004). T3-4a colorectal cancer patients with high miR-21 expression had significantly shorter recurrence-free survival than those with low miR-21 expression. When analyzing colon and rectal cancer separately, high expression of miR-21 was an independent prognostic factor of unfavorable recurrence-free survival in T3-4a colon cancer patients (P = 0.038, HR = 2.45; 95% CI = 1.05-5.72) but not in T3-4a rectal cancer patients. In a sub-classification analysis, high miR-21 expression was associated with shorter recurrence-free survival in the stage II cancer (P = 0.001) but not in the stage III subgroup (P = 0.267).

Conclusions: Stromal miR-21 expression is related to the expression of E-cadherin and metastasis-associated protein1 in colorectal cancer. Stage II colorectal cancer patients with high levels of miR-21 are at higher risk for tumor recurrence and should be considered for more intensive treatment.

No MeSH data available.


Related in: MedlinePlus

Forest plot of meta-analysis for the association of high miR-21 expression and overall survival in colorectal cancer patients. High miR-21 expression is associated with poor overall survival in colon cancer patients but not in rectal cancer. CI, confidence interval; CC, colon cancer; RC, rectal cancer; CRC, colorectal cancer; OS, overall survival.
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Fig4: Forest plot of meta-analysis for the association of high miR-21 expression and overall survival in colorectal cancer patients. High miR-21 expression is associated with poor overall survival in colon cancer patients but not in rectal cancer. CI, confidence interval; CC, colon cancer; RC, rectal cancer; CRC, colorectal cancer; OS, overall survival.

Mentions: A total of 10 studies were included for the meta-analysis and their characteristics are summarized in Table 4 [13,18-20,29-34]. High heterogeneity was found in the analysis. For all CRC patients, high miR-21 expression was significantly associated with poor RFS (HR = 1.327, 95% CI = 1.053-1.673, Figure 3) and poor OS (HR = 1.272, 95% CI = 1.065-1.519, Figure 4). In subgroup analysis, the high miR-21 expression was significantly correlated with poor RFS and OS in colon cancer patients (HR = 1.423, 95% CI = 1.280-1.582; HR = 1.357, 95% CI = 1.102-1.672, respectively), but not in rectal cancer or CRC patients.Figure 3


Stromal expression of miR-21 in T3-4a colorectal cancer is an independent predictor of early tumor relapse.

Kang WK, Lee JK, Oh ST, Lee SH, Jung CK - BMC Gastroenterol (2015)

Forest plot of meta-analysis for the association of high miR-21 expression and overall survival in colorectal cancer patients. High miR-21 expression is associated with poor overall survival in colon cancer patients but not in rectal cancer. CI, confidence interval; CC, colon cancer; RC, rectal cancer; CRC, colorectal cancer; OS, overall survival.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4308857&req=5

Fig4: Forest plot of meta-analysis for the association of high miR-21 expression and overall survival in colorectal cancer patients. High miR-21 expression is associated with poor overall survival in colon cancer patients but not in rectal cancer. CI, confidence interval; CC, colon cancer; RC, rectal cancer; CRC, colorectal cancer; OS, overall survival.
Mentions: A total of 10 studies were included for the meta-analysis and their characteristics are summarized in Table 4 [13,18-20,29-34]. High heterogeneity was found in the analysis. For all CRC patients, high miR-21 expression was significantly associated with poor RFS (HR = 1.327, 95% CI = 1.053-1.673, Figure 3) and poor OS (HR = 1.272, 95% CI = 1.065-1.519, Figure 4). In subgroup analysis, the high miR-21 expression was significantly correlated with poor RFS and OS in colon cancer patients (HR = 1.423, 95% CI = 1.280-1.582; HR = 1.357, 95% CI = 1.102-1.672, respectively), but not in rectal cancer or CRC patients.Figure 3

Bottom Line: Patients with neoadjuvant therapy and distant metastasis at presentation were excluded.Immunohistochemistry was used to detect E-cadherin and metastasis-associated protein1 expression.Stage II colorectal cancer patients with high levels of miR-21 are at higher risk for tumor recurrence and should be considered for more intensive treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. wonkkang@catholic.ac.kr.

ABSTRACT

Background: MicroRNA-21 (miR-21) is an oncogenic microRNA that regulates the expression of multiple cancer-related target genes. miR-21 has been associated with progression of some types of cancer. Metastasis-associated protein1 expression and loss of E-cadherin expression are correlated with cancer progression and metastasis in many cancer types. In advanced colorectal cancer, the clinical significance of miR-21 expression remains unclear. We aimed to investigate the impact of miR-21 expression in advanced colorectal cancer and its correlation with target proteins associated with colorectal cancer progression.

Methods: From 2004 to 2007, 277 consecutive patients with T3-4a colorectal cancer treated with R0 surgical resection were included. Patients with neoadjuvant therapy and distant metastasis at presentation were excluded. The expression of miR-21 was investigated by in situ hybridization. Immunohistochemistry was used to detect E-cadherin and metastasis-associated protein1 expression.

Results: High stromal expression of miR-21 was found in 76 of 277 (27.4%) colorectal cancer samples and was correlated with low E-cadherin expression (P = 0.019) and high metastasis-associated protein1 expression (P = 0.004). T3-4a colorectal cancer patients with high miR-21 expression had significantly shorter recurrence-free survival than those with low miR-21 expression. When analyzing colon and rectal cancer separately, high expression of miR-21 was an independent prognostic factor of unfavorable recurrence-free survival in T3-4a colon cancer patients (P = 0.038, HR = 2.45; 95% CI = 1.05-5.72) but not in T3-4a rectal cancer patients. In a sub-classification analysis, high miR-21 expression was associated with shorter recurrence-free survival in the stage II cancer (P = 0.001) but not in the stage III subgroup (P = 0.267).

Conclusions: Stromal miR-21 expression is related to the expression of E-cadherin and metastasis-associated protein1 in colorectal cancer. Stage II colorectal cancer patients with high levels of miR-21 are at higher risk for tumor recurrence and should be considered for more intensive treatment.

No MeSH data available.


Related in: MedlinePlus