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PPP1R12A Copy Number Is Associated with Clinical Outcomes of Stage III CRC Receiving Oxaliplatin-Based Chemotherapy.

Zhang C, Li A, Li H, Peng K, Wei Q, Lin M, Liu Z, Yin L, Li J - Mediators Inflamm. (2015)

Bottom Line: Genomic DNA was extracted and purified from paraffin-embedded sections.Statistical analysis demonstrated that low PPP1R12A RCN was associated with poor RFS (HR = 2.186, 95% CI: 1.293-3.696; P = 0.003) and OS (HR = 2.782, 95% CI: 1.531-5.052; P < 0.001).Additionally, when patients were stratified according to subgroups of stage III and tumor location, poor RFS and OS were also observed in the low PPP1R12A RCN group with significance (RFS: IIIB HR = 2.870, P < 0.001; colon HR = 1.910, P = 0.037; OS: IIIB HR = 3.527, P < 0.001; IIIC HR = 2.662, P = 0.049; rectum HR = 4.229, P = 0.002).

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

ABSTRACT

Aim: To investigate the correlation between PPP1R12A gene copy number and clinical outcomes of oxaliplatin-based regimen in stage III colorectal cancer (CRC).

Methods: A total of 139 paraffin-embedded tissue samples of stage III CRC patients who received oxaliplatin-based treatment after radical surgery were recruited. Genomic DNA was extracted and purified from paraffin-embedded sections. Quantitative PCR methods were used to detect the relative copy number (RCN) of PPP1R12A.

Results: Statistical analysis demonstrated that low PPP1R12A RCN was associated with poor RFS (HR = 2.186, 95% CI: 1.293-3.696; P = 0.003) and OS (HR = 2.782, 95% CI: 1.531-5.052; P < 0.001). Additionally, when patients were stratified according to subgroups of stage III and tumor location, poor RFS and OS were also observed in the low PPP1R12A RCN group with significance (RFS: IIIB HR = 2.870, P < 0.001; colon HR = 1.910, P = 0.037; OS: IIIB HR = 3.527, P < 0.001; IIIC HR = 2.662, P = 0.049; rectum HR = 4.229, P = 0.002).

Conclusion: Our findings suggest the copy number of PPP1R12A can independently predict recurrence and overall survival of stage III colorectal cancer patients receiving oxaliplatin-based chemotherapy.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier survival curves of patients with stage III, IIIB, and IIIC disease receiving oxaliplatin-based chemotherapy. (a) OS in total stage III; (b) OS in stage IIIB; (c) OS in stage IIIC. MST: median survival time.
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fig3: Kaplan-Meier survival curves of patients with stage III, IIIB, and IIIC disease receiving oxaliplatin-based chemotherapy. (a) OS in total stage III; (b) OS in stage IIIB; (c) OS in stage IIIC. MST: median survival time.

Mentions: Among the 139 stage III CRC patients, 44 (31.7%) patients died during the follow-up. The median overall periods were 47 (±11.1) months in the low RCN group while the OS were not reached in the high gene copy number group (Figure 3(a)). Both the univariate analysis and the multivariate analysis of OS were shown in Table 3. Poor differentiation (HR = 2.310, P = 0.011), high lymph node metastasis (lymph  node ≥ 4: HR = 2.750, P = 0.001), high TNM stage (IIIC: HR = 3.613, P < 0.001), and low PPP1R12A RCN (RCN < 0.37: HR = 2.782, P < 0.001) were shown to be significantly associated with poor OS. Furthermore, the multivariate analysis showed that poor differentiation (HR = 2.242, P = 0.021), TNM stage (IIIC: HR = 3.913, P < 0.001), and low PPP1R12A (HR = 2.976, P = 0.001) remained independent predictive factors of poor OS. The Kaplan-Meier analysis was also used to assess the correlation between PPP1R12A copy number and overall survival. The log-rank test showed that patients with low PPP1R12A copy number were associated with a statistically significant poor OS (P < 0.001) (Figure 3(a)). Further analysis in different subgroups showed low RCN was still associated with OS in IIIB (IIIB: P < 0.001, HR = 3.527) and IIIC (IIIC: P = 0.049, HR = 2.662) patients (Figures 3(b) and 3(c)). In the rectum subgroup, low RCN was significantly correlated with poor OS (P = 0.002, HR = 4.229) (Figure 4(b)). Similarly, patients with low PPP1R12A RCN showed a trend towards poor OS in colon subgroup (Figure 4(a)  P = 0.086, HR = 1.957).


PPP1R12A Copy Number Is Associated with Clinical Outcomes of Stage III CRC Receiving Oxaliplatin-Based Chemotherapy.

Zhang C, Li A, Li H, Peng K, Wei Q, Lin M, Liu Z, Yin L, Li J - Mediators Inflamm. (2015)

Kaplan-Meier survival curves of patients with stage III, IIIB, and IIIC disease receiving oxaliplatin-based chemotherapy. (a) OS in total stage III; (b) OS in stage IIIB; (c) OS in stage IIIC. MST: median survival time.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4465766&req=5

fig3: Kaplan-Meier survival curves of patients with stage III, IIIB, and IIIC disease receiving oxaliplatin-based chemotherapy. (a) OS in total stage III; (b) OS in stage IIIB; (c) OS in stage IIIC. MST: median survival time.
Mentions: Among the 139 stage III CRC patients, 44 (31.7%) patients died during the follow-up. The median overall periods were 47 (±11.1) months in the low RCN group while the OS were not reached in the high gene copy number group (Figure 3(a)). Both the univariate analysis and the multivariate analysis of OS were shown in Table 3. Poor differentiation (HR = 2.310, P = 0.011), high lymph node metastasis (lymph  node ≥ 4: HR = 2.750, P = 0.001), high TNM stage (IIIC: HR = 3.613, P < 0.001), and low PPP1R12A RCN (RCN < 0.37: HR = 2.782, P < 0.001) were shown to be significantly associated with poor OS. Furthermore, the multivariate analysis showed that poor differentiation (HR = 2.242, P = 0.021), TNM stage (IIIC: HR = 3.913, P < 0.001), and low PPP1R12A (HR = 2.976, P = 0.001) remained independent predictive factors of poor OS. The Kaplan-Meier analysis was also used to assess the correlation between PPP1R12A copy number and overall survival. The log-rank test showed that patients with low PPP1R12A copy number were associated with a statistically significant poor OS (P < 0.001) (Figure 3(a)). Further analysis in different subgroups showed low RCN was still associated with OS in IIIB (IIIB: P < 0.001, HR = 3.527) and IIIC (IIIC: P = 0.049, HR = 2.662) patients (Figures 3(b) and 3(c)). In the rectum subgroup, low RCN was significantly correlated with poor OS (P = 0.002, HR = 4.229) (Figure 4(b)). Similarly, patients with low PPP1R12A RCN showed a trend towards poor OS in colon subgroup (Figure 4(a)  P = 0.086, HR = 1.957).

Bottom Line: Genomic DNA was extracted and purified from paraffin-embedded sections.Statistical analysis demonstrated that low PPP1R12A RCN was associated with poor RFS (HR = 2.186, 95% CI: 1.293-3.696; P = 0.003) and OS (HR = 2.782, 95% CI: 1.531-5.052; P < 0.001).Additionally, when patients were stratified according to subgroups of stage III and tumor location, poor RFS and OS were also observed in the low PPP1R12A RCN group with significance (RFS: IIIB HR = 2.870, P < 0.001; colon HR = 1.910, P = 0.037; OS: IIIB HR = 3.527, P < 0.001; IIIC HR = 2.662, P = 0.049; rectum HR = 4.229, P = 0.002).

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

ABSTRACT

Aim: To investigate the correlation between PPP1R12A gene copy number and clinical outcomes of oxaliplatin-based regimen in stage III colorectal cancer (CRC).

Methods: A total of 139 paraffin-embedded tissue samples of stage III CRC patients who received oxaliplatin-based treatment after radical surgery were recruited. Genomic DNA was extracted and purified from paraffin-embedded sections. Quantitative PCR methods were used to detect the relative copy number (RCN) of PPP1R12A.

Results: Statistical analysis demonstrated that low PPP1R12A RCN was associated with poor RFS (HR = 2.186, 95% CI: 1.293-3.696; P = 0.003) and OS (HR = 2.782, 95% CI: 1.531-5.052; P < 0.001). Additionally, when patients were stratified according to subgroups of stage III and tumor location, poor RFS and OS were also observed in the low PPP1R12A RCN group with significance (RFS: IIIB HR = 2.870, P < 0.001; colon HR = 1.910, P = 0.037; OS: IIIB HR = 3.527, P < 0.001; IIIC HR = 2.662, P = 0.049; rectum HR = 4.229, P = 0.002).

Conclusion: Our findings suggest the copy number of PPP1R12A can independently predict recurrence and overall survival of stage III colorectal cancer patients receiving oxaliplatin-based chemotherapy.

No MeSH data available.


Related in: MedlinePlus