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Serum miRNA expression profile as a prognostic biomarker of stage II/III colorectal adenocarcinoma.

Li J, Liu Y, Wang C, Deng T, Liang H, Wang Y, Huang D, Fan Q, Wang X, Ning T, Liu R, Zhang CY, Zen K, Chen X, Ba Y - Sci Rep (2015)

Bottom Line: Using individual RT-qPCR verification in 175 stage II/III CRC patients, we identified that miR-145, miR-106a and miR-17-3p were significantly differentially expressed between pre- and post-operative CRC patients and between pre-operative CRC patients and normal controls (P < 0.0001).Furthermore, using the Kaplan-Meier method and Cox proportional hazards analysis, we found that miR-17-3p and miR-106a were powerful and independent prognostic indicators and that high levels of these miRNAs were associated with shorter disease-free survival (DFS) (P < 0.0001 for miR-17-3p and P = 0.001 for miR-106a).The present study reveals novel serum-miRNA-based biomarkers for monitoring tumor dynamics as well as for predicting disease recurrence in patients with stage II/III CRC.

View Article: PubMed Central - PubMed

Affiliation: 1] Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Rd., Tiyuanbei, Tianjin 300060, China [2] Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Rd., Nanjing 210093, Nanjing, China.

ABSTRACT
We sought to identify a serum miRNA expression profile to improve disease surveillance and to predict post-operative disease recurrence for stage II/III colorectal cancer (CRC) patients. Using the TaqMan Low-Density Array (TLDA), we performed an initial survey to analyze 749 miRNAs in the pooled serum of 20 paired pre- and post-operative CRC patients and 20 matched normal subjects. Using individual RT-qPCR verification in 175 stage II/III CRC patients, we identified that miR-145, miR-106a and miR-17-3p were significantly differentially expressed between pre- and post-operative CRC patients and between pre-operative CRC patients and normal controls (P < 0.0001). The area under the ROC curve (AUC) for the three-miRNA panel was 0.886 (95% CI 0.850-0.921) for discriminating between pre-operative CRC patients and normal subjects and 0.850 (95% CI 0.809-0.891) for discriminating between pre- and post-operative CRC patients. Furthermore, using the Kaplan-Meier method and Cox proportional hazards analysis, we found that miR-17-3p and miR-106a were powerful and independent prognostic indicators and that high levels of these miRNAs were associated with shorter disease-free survival (DFS) (P < 0.0001 for miR-17-3p and P = 0.001 for miR-106a). The present study reveals novel serum-miRNA-based biomarkers for monitoring tumor dynamics as well as for predicting disease recurrence in patients with stage II/III CRC.

No MeSH data available.


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A Kaplan–Meier curve estimates the association of miRNAs and the survival of patients with stage II/III colorectal cancer who received adjuvant chemotherapy.(A) Association between the expression of miR-17-3p and miR-106a and disease-free survival (DFS) in patients with stage II/III CRC who had received chemotherapy. (B) Associations between the expression of miR-17-3p and miR-106a and DFS in patients with stage II CRC who had received chemotherapy. (C) Association between the expression of miR-17-3p and miR-106a and DFS among patients with stage III CRC who had received chemotherapy.
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f5: A Kaplan–Meier curve estimates the association of miRNAs and the survival of patients with stage II/III colorectal cancer who received adjuvant chemotherapy.(A) Association between the expression of miR-17-3p and miR-106a and disease-free survival (DFS) in patients with stage II/III CRC who had received chemotherapy. (B) Associations between the expression of miR-17-3p and miR-106a and DFS in patients with stage II CRC who had received chemotherapy. (C) Association between the expression of miR-17-3p and miR-106a and DFS among patients with stage III CRC who had received chemotherapy.

Mentions: We analyzed the associations between miRNA expression and therapeutic outcomes in stage II and III cancer patients treated with adjuvant chemotherapy. Receipt of adjuvant chemotherapy was beneficial for patients with either stage II or stage III cancer, although this benefit was only significant for stage III patients (P = 0.017). For individuals who received adjuvant therapy, high expression of miR-17-3p or miR-106a predicted a more rapid tumor recurrence (P = 0.002 and P < 0.0001, respectively), providing preliminary support that high levels of miR-17-3p and miR-106a are associated with poor therapeutic outcomes (Fig. 5A). Additionally, because the benefit from adjuvant chemotherapy was not consistent for patients with different disease stages, we then separately evaluated the association of miRNA levels and therapeutic outcomes in patients with stages II and III. Of the 39 patients with stage II CRC who had received adjuvant chemotherapy, high levels of miR-17-3p and miR-106a were associated with poor therapeutic outcomes (P = 0.055 and P = 0.038, respectively) (Fig. 5B). For 41 patients with stage III CRC who had received adjuvant chemotherapy, high levels of miR-17-3p and miR-106a were also associated with shorter DFS (P = 0.038 and P = 0.001, respectively) (Fig. 5C). These results show that miR-17-3p and miR-106a were associated with poor therapeutic outcomes in CRC patients with localized disease who had already undergone curative surgical resection and received adjuvant chemotherapy.


Serum miRNA expression profile as a prognostic biomarker of stage II/III colorectal adenocarcinoma.

Li J, Liu Y, Wang C, Deng T, Liang H, Wang Y, Huang D, Fan Q, Wang X, Ning T, Liu R, Zhang CY, Zen K, Chen X, Ba Y - Sci Rep (2015)

A Kaplan–Meier curve estimates the association of miRNAs and the survival of patients with stage II/III colorectal cancer who received adjuvant chemotherapy.(A) Association between the expression of miR-17-3p and miR-106a and disease-free survival (DFS) in patients with stage II/III CRC who had received chemotherapy. (B) Associations between the expression of miR-17-3p and miR-106a and DFS in patients with stage II CRC who had received chemotherapy. (C) Association between the expression of miR-17-3p and miR-106a and DFS among patients with stage III CRC who had received chemotherapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4528229&req=5

f5: A Kaplan–Meier curve estimates the association of miRNAs and the survival of patients with stage II/III colorectal cancer who received adjuvant chemotherapy.(A) Association between the expression of miR-17-3p and miR-106a and disease-free survival (DFS) in patients with stage II/III CRC who had received chemotherapy. (B) Associations between the expression of miR-17-3p and miR-106a and DFS in patients with stage II CRC who had received chemotherapy. (C) Association between the expression of miR-17-3p and miR-106a and DFS among patients with stage III CRC who had received chemotherapy.
Mentions: We analyzed the associations between miRNA expression and therapeutic outcomes in stage II and III cancer patients treated with adjuvant chemotherapy. Receipt of adjuvant chemotherapy was beneficial for patients with either stage II or stage III cancer, although this benefit was only significant for stage III patients (P = 0.017). For individuals who received adjuvant therapy, high expression of miR-17-3p or miR-106a predicted a more rapid tumor recurrence (P = 0.002 and P < 0.0001, respectively), providing preliminary support that high levels of miR-17-3p and miR-106a are associated with poor therapeutic outcomes (Fig. 5A). Additionally, because the benefit from adjuvant chemotherapy was not consistent for patients with different disease stages, we then separately evaluated the association of miRNA levels and therapeutic outcomes in patients with stages II and III. Of the 39 patients with stage II CRC who had received adjuvant chemotherapy, high levels of miR-17-3p and miR-106a were associated with poor therapeutic outcomes (P = 0.055 and P = 0.038, respectively) (Fig. 5B). For 41 patients with stage III CRC who had received adjuvant chemotherapy, high levels of miR-17-3p and miR-106a were also associated with shorter DFS (P = 0.038 and P = 0.001, respectively) (Fig. 5C). These results show that miR-17-3p and miR-106a were associated with poor therapeutic outcomes in CRC patients with localized disease who had already undergone curative surgical resection and received adjuvant chemotherapy.

Bottom Line: Using individual RT-qPCR verification in 175 stage II/III CRC patients, we identified that miR-145, miR-106a and miR-17-3p were significantly differentially expressed between pre- and post-operative CRC patients and between pre-operative CRC patients and normal controls (P < 0.0001).Furthermore, using the Kaplan-Meier method and Cox proportional hazards analysis, we found that miR-17-3p and miR-106a were powerful and independent prognostic indicators and that high levels of these miRNAs were associated with shorter disease-free survival (DFS) (P < 0.0001 for miR-17-3p and P = 0.001 for miR-106a).The present study reveals novel serum-miRNA-based biomarkers for monitoring tumor dynamics as well as for predicting disease recurrence in patients with stage II/III CRC.

View Article: PubMed Central - PubMed

Affiliation: 1] Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Rd., Tiyuanbei, Tianjin 300060, China [2] Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Rd., Nanjing 210093, Nanjing, China.

ABSTRACT
We sought to identify a serum miRNA expression profile to improve disease surveillance and to predict post-operative disease recurrence for stage II/III colorectal cancer (CRC) patients. Using the TaqMan Low-Density Array (TLDA), we performed an initial survey to analyze 749 miRNAs in the pooled serum of 20 paired pre- and post-operative CRC patients and 20 matched normal subjects. Using individual RT-qPCR verification in 175 stage II/III CRC patients, we identified that miR-145, miR-106a and miR-17-3p were significantly differentially expressed between pre- and post-operative CRC patients and between pre-operative CRC patients and normal controls (P < 0.0001). The area under the ROC curve (AUC) for the three-miRNA panel was 0.886 (95% CI 0.850-0.921) for discriminating between pre-operative CRC patients and normal subjects and 0.850 (95% CI 0.809-0.891) for discriminating between pre- and post-operative CRC patients. Furthermore, using the Kaplan-Meier method and Cox proportional hazards analysis, we found that miR-17-3p and miR-106a were powerful and independent prognostic indicators and that high levels of these miRNAs were associated with shorter disease-free survival (DFS) (P < 0.0001 for miR-17-3p and P = 0.001 for miR-106a). The present study reveals novel serum-miRNA-based biomarkers for monitoring tumor dynamics as well as for predicting disease recurrence in patients with stage II/III CRC.

No MeSH data available.


Related in: MedlinePlus