INTRODUCTION. The circadian timing system (CTS) is important in regulating several physiological processes in mammals on 24 hour intervals; it is generated by a feedback oscillatory loop that involves a set of “clock genes” including CLOCK, BMAL1, PER (1, 2 and 3) and CRY (1 and 2). Experimental and clinical evidence indicates a pivotal role of CTS in cancer development and progression. It is also well-known that sex remains an independent risk factor with an important impact on the patient survival. We analyzed the expression levels of a set of microRNA (miR-206-219-192-194-132) and SNPs (rs1801260T>C, rs11133391T>C, rs11133373C>G) related to CLOCK gene in 83 mCRC pts retrospectively enrolled. METHODS. Population’s characteristics were: median age 59 years (30-85); male/female (M/F) 50/33; median follow-up 25 months; median overall survival (OS) 35 months (CI 95% 22-47). DNA and miRNA for analyses were extracted from FFPE normal and tumor tissue, respectively. OS was the primary study endpoint. RESULTS. OS was significantly better in F: M/F=31/50 months (CI 95% 22-39/35-64) p=0.03. We found an association between OS and miRNA levels or SNP only stratifying the population by sex: better OS of F was related to high expression level (H) of miR206 (p=0.0003), miR219 (p=0.002) and miR194 (p=0.02), and low expression (L) of miR132 (p=0.06). Genotypes rs1801260T/T (p=0.07) rs11133391T/T (p=0.06), rs11133373C/C (p=0.01) also showed an association with better OS in F. Median OS of F was further increased up to 87 months by simultaneously presence of beneficial expression of ≥2 miRNAs and of rs11133391T/T . Moreover, while in female H of miR-206,-219 and genotypes rs11133391T/T and rs11133373C/C show a better OS, in male seem to be even negative markers of survival. CONCLUSIONS. These results highlight that OS in mCRC pts could be associated to genetic variants and miRNA levels in a gender-related manner and we identify a subgroup of female pts who shows a better prognosis.

Differente sopravvivenza tra maschi e femmine associata a polimorfismi e miRNA correlati ai clock-genes in pazienti con cancro metastatico del colon-retto

RICCIARDI, TERESA
2015

Abstract

INTRODUCTION. The circadian timing system (CTS) is important in regulating several physiological processes in mammals on 24 hour intervals; it is generated by a feedback oscillatory loop that involves a set of “clock genes” including CLOCK, BMAL1, PER (1, 2 and 3) and CRY (1 and 2). Experimental and clinical evidence indicates a pivotal role of CTS in cancer development and progression. It is also well-known that sex remains an independent risk factor with an important impact on the patient survival. We analyzed the expression levels of a set of microRNA (miR-206-219-192-194-132) and SNPs (rs1801260T>C, rs11133391T>C, rs11133373C>G) related to CLOCK gene in 83 mCRC pts retrospectively enrolled. METHODS. Population’s characteristics were: median age 59 years (30-85); male/female (M/F) 50/33; median follow-up 25 months; median overall survival (OS) 35 months (CI 95% 22-47). DNA and miRNA for analyses were extracted from FFPE normal and tumor tissue, respectively. OS was the primary study endpoint. RESULTS. OS was significantly better in F: M/F=31/50 months (CI 95% 22-39/35-64) p=0.03. We found an association between OS and miRNA levels or SNP only stratifying the population by sex: better OS of F was related to high expression level (H) of miR206 (p=0.0003), miR219 (p=0.002) and miR194 (p=0.02), and low expression (L) of miR132 (p=0.06). Genotypes rs1801260T/T (p=0.07) rs11133391T/T (p=0.06), rs11133373C/C (p=0.01) also showed an association with better OS in F. Median OS of F was further increased up to 87 months by simultaneously presence of beneficial expression of ≥2 miRNAs and of rs11133391T/T . Moreover, while in female H of miR-206,-219 and genotypes rs11133391T/T and rs11133373C/C show a better OS, in male seem to be even negative markers of survival. CONCLUSIONS. These results highlight that OS in mCRC pts could be associated to genetic variants and miRNA levels in a gender-related manner and we identify a subgroup of female pts who shows a better prognosis.
2015
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11576/2629249
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