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Gender effects of single nucleotide polymorphisms and miRNAs targeting clock-genes in metastatic colorectal cancer patients (mCRC)

View Article: PubMed Central - PubMed

ABSTRACT

The circadian system is composed of a set of clock-genes including PERIOD, CLOCK, BMAL1 and CRY. Disrupting this system promotes cancer development and progression. The expression levels of miR-206, miR-219, miR-192, miR-194 and miR-132 regulating clock-genes and three functional polymorphisms rs11133373 C/G, rs1801260 T/C, rs11133391 T/C in CLOCK sequence were associated with the survival of 83 mCRC patients (50 males and 33 females). Longer overall survival (OS) was observed in women compared to men, 50 versus 31 months. This difference was associated with rs11133373 C/C genotype (p = 0.01), rs1801260 T/C+C/C genotype (p = 0.06) and rs11133391 T/T genotype (p = 0.06). Moreover women expressing high levels (H) of miR-192 (p = 0.03), miR-206 (p = 0.003), miR-194 (p = 0.02) and miR-219 (p = 0.002) had a longer OS compared to men. In women longer OS was reinforced by the simultaneous presence of two or more H-miR, 58 months versus 15 months (p = 0.0008); in this group of women an OS of 87 months was reached with the additional presence of rs11133391T/T genotype (p = 0.02). In this study we identified a subgroup of female patients who seems to have a better prognosis. Personalized medicine should prospectively take into account both genetic and gender differences.

No MeSH data available.


Kaplan-Meier plot of Progression Free Survival (PFS) at 2 years and Overall Survival (OS) at 3 years of patients according to sex.
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f1: Kaplan-Meier plot of Progression Free Survival (PFS) at 2 years and Overall Survival (OS) at 3 years of patients according to sex.

Mentions: Patient data are shown in Table 1. Most of the patients (78%) received first line triplet chemotherapy (fluorouracil plus oxaliplatin and irinotecan) ± monoclonal antibody, 82% were KRAS wild-type and 55% of them were resected for liver metastases after induction chemotherapy. Median progression free survival (PFS) was 14 months and median overall survival (OS) was 35 months. Women were observed to have better median PFS and OS than men, 19 months versus 12 months (2 years-PFS 25.8% vs 12.3%, p = 0.03) and 50 months versus 31 months (3 years-OS 61.5% vs 35.9%, p = 0.03), respectively (Fig. 1 and Table 1). Differences in prognostic factors between the female and male groups were also observed for age and chronomodulated therapy (p = 0.04), as reported in Table 1.


Gender effects of single nucleotide polymorphisms and miRNAs targeting clock-genes in metastatic colorectal cancer patients (mCRC)
Kaplan-Meier plot of Progression Free Survival (PFS) at 2 years and Overall Survival (OS) at 3 years of patients according to sex.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036027&req=5

f1: Kaplan-Meier plot of Progression Free Survival (PFS) at 2 years and Overall Survival (OS) at 3 years of patients according to sex.
Mentions: Patient data are shown in Table 1. Most of the patients (78%) received first line triplet chemotherapy (fluorouracil plus oxaliplatin and irinotecan) ± monoclonal antibody, 82% were KRAS wild-type and 55% of them were resected for liver metastases after induction chemotherapy. Median progression free survival (PFS) was 14 months and median overall survival (OS) was 35 months. Women were observed to have better median PFS and OS than men, 19 months versus 12 months (2 years-PFS 25.8% vs 12.3%, p = 0.03) and 50 months versus 31 months (3 years-OS 61.5% vs 35.9%, p = 0.03), respectively (Fig. 1 and Table 1). Differences in prognostic factors between the female and male groups were also observed for age and chronomodulated therapy (p = 0.04), as reported in Table 1.

View Article: PubMed Central - PubMed

ABSTRACT

The circadian system is composed of a set of clock-genes including PERIOD, CLOCK, BMAL1 and CRY. Disrupting this system promotes cancer development and progression. The expression levels of miR-206, miR-219, miR-192, miR-194 and miR-132 regulating clock-genes and three functional polymorphisms rs11133373 C/G, rs1801260 T/C, rs11133391 T/C in CLOCK sequence were associated with the survival of 83 mCRC patients (50 males and 33 females). Longer overall survival (OS) was observed in women compared to men, 50 versus 31 months. This difference was associated with rs11133373 C/C genotype (p = 0.01), rs1801260 T/C+C/C genotype (p = 0.06) and rs11133391 T/T genotype (p = 0.06). Moreover women expressing high levels (H) of miR-192 (p = 0.03), miR-206 (p = 0.003), miR-194 (p = 0.02) and miR-219 (p = 0.002) had a longer OS compared to men. In women longer OS was reinforced by the simultaneous presence of two or more H-miR, 58 months versus 15 months (p = 0.0008); in this group of women an OS of 87 months was reached with the additional presence of rs11133391T/T genotype (p = 0.02). In this study we identified a subgroup of female patients who seems to have a better prognosis. Personalized medicine should prospectively take into account both genetic and gender differences.

No MeSH data available.