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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: The expression of miR-21 was investigated by in situ hybridization.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

Association between miR-21 expression and recurrence-free survival in patients with T3-4a colorectal cancer. Kaplan-Meier survival curves for recurrence-free survival in all (A), stage II (B) and stage III (C) cancer patients according to miR-21 expression status. (A) High miR-21 expression is associated with recurrence-free survival in colon cancer patients but not in rectal cancer patients. (B) For the 138 patients with stage II cancer, the association between high miR-21 expression and recurrence-free survival is statistically significant only in colon cancer patients. (C) Among 277 stage III cancer patients, high miR-21 expression is not associated with poor recurrence-free survival.
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Fig2: Association between miR-21 expression and recurrence-free survival in patients with T3-4a colorectal cancer. Kaplan-Meier survival curves for recurrence-free survival in all (A), stage II (B) and stage III (C) cancer patients according to miR-21 expression status. (A) High miR-21 expression is associated with recurrence-free survival in colon cancer patients but not in rectal cancer patients. (B) For the 138 patients with stage II cancer, the association between high miR-21 expression and recurrence-free survival is statistically significant only in colon cancer patients. (C) Among 277 stage III cancer patients, high miR-21 expression is not associated with poor recurrence-free survival.

Mentions: In all 277 CRC patients, variables significantly associated with RFS included miR-21 expression (P = 0.010, Figure 2A), histological differentiation (P = 0.031), pT stage (P = 0.0005), lymph node metastasis (P = 0.00001), and serum CEA level (P =0.006) (Table 2). In a multivariate analysis, high levels of miR-21 (P = 0.007, HR = 2.24; 95% CI = 1.25-4.02), pT stage, lymph node metastasis, and serum CEA level were independent prognostic factors for unfavorable RFS (Table 3). However, the OS rate was not associated with the expression levels of miR-21, E-cadherin or MTA1.Figure 2


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)

Association between miR-21 expression and recurrence-free survival in patients with T3-4a colorectal cancer. Kaplan-Meier survival curves for recurrence-free survival in all (A), stage II (B) and stage III (C) cancer patients according to miR-21 expression status. (A) High miR-21 expression is associated with recurrence-free survival in colon cancer patients but not in rectal cancer patients. (B) For the 138 patients with stage II cancer, the association between high miR-21 expression and recurrence-free survival is statistically significant only in colon cancer patients. (C) Among 277 stage III cancer patients, high miR-21 expression is not associated with poor recurrence-free survival.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Association between miR-21 expression and recurrence-free survival in patients with T3-4a colorectal cancer. Kaplan-Meier survival curves for recurrence-free survival in all (A), stage II (B) and stage III (C) cancer patients according to miR-21 expression status. (A) High miR-21 expression is associated with recurrence-free survival in colon cancer patients but not in rectal cancer patients. (B) For the 138 patients with stage II cancer, the association between high miR-21 expression and recurrence-free survival is statistically significant only in colon cancer patients. (C) Among 277 stage III cancer patients, high miR-21 expression is not associated with poor recurrence-free survival.
Mentions: In all 277 CRC patients, variables significantly associated with RFS included miR-21 expression (P = 0.010, Figure 2A), histological differentiation (P = 0.031), pT stage (P = 0.0005), lymph node metastasis (P = 0.00001), and serum CEA level (P =0.006) (Table 2). In a multivariate analysis, high levels of miR-21 (P = 0.007, HR = 2.24; 95% CI = 1.25-4.02), pT stage, lymph node metastasis, and serum CEA level were independent prognostic factors for unfavorable RFS (Table 3). However, the OS rate was not associated with the expression levels of miR-21, E-cadherin or MTA1.Figure 2

Bottom Line: The expression of miR-21 was investigated by in situ hybridization.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