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Redefining high-risk patients with stage II colon cancer by risk index and microRNA-21: results from a population-based cohort.

ABSTRACT: BACKGROUND: The aim of the present study was to analyse the prognostic value of microRNA-21 (miRNA-21) in patients with stage II colon cancer aiming at a risk index for this group of patients. METHODS: A population-based cohort of 554 patients was included. MicroRNA-21 was analysed by qPCR based on tumour tissue. An index was created using the coefficients obtained from a collective multiple Cox regression. The entire procedure was cross-validated (10-fold). The performance of the index was quantified by time-dependent receiver operating characteristics curves. RESULTS: High miRNA-21 expression was associated with an unfavourable recurrence-free cancer-specific survival (RF-CSS), hazard ratio 1.35 (95% confidence interval, 1.03-1.76) (P=0.028). The generated RF-CSS index divided the traditional high-risk patients into subgroups with 5-year RF-CSS rates of 87% and 73%, respectively (P<0.001). The overall survival (OS) index identified three different subgroups (P<0.001). Cross-validated 5-year OS rates were 88%, 68%, and 50%, respectively. CONCLUSIONS: This population-based study supports miRNA-21 as an additional prognostic biomarker in patients with stage II colon cancer. Furthermore, the introduction of a risk index may guide the use of postoperative adjuvant treatment in a more appropriate way compared with current practice.

SUBMITTER: Hansen TF

PROVIDER: S-EPMC4183843 | biostudies-other | 2014 Sep

REPOSITORIES: biostudies-other

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Project description:MicroRNAs (miRNAs) have been implicated in the incidence and progression of cancer. It has been proposed that single nucleotide polymorphisms (SNPs) influence cancer risk due to their position within genes involved in miRNA synthesis and regulation.Genes directly and indirectly involved in miRNA biogenesis were identified from the literature. We then identified SNPs within these regions. Using genome-wide association study data we evaluated associations between biogenesis-related SNPs with colon cancer risk and their corresponding mRNA expression in normal colonic mucosa and carcinoma and difference in expression between the two tissues. SNPs that were associated with either altered colon cancer risk or with mRNA expression were evaluated for associations with altered miRNA expression.Eleven SNPs were associated (P?<?0.05) with colon cancer risk, and two of these variants remained significant after correction for multiple comparisons (PHolm?<?0.05): rs1967327 (PRKRA) (ORdom?=?0.78, 95 % CI 0.66-0.92) and rs4548444 (MAPKAP2) (ORrec?=?1.67, 95 % CI 1.12-2.48). Of these two SNPs, rs4548444 (MAPKAP2), was associated with significantly altered miRNA expression levels in normal colonic mucosa, with nine miRNAs upregulated among individuals homozygous rare (GG) for rs4548444. One SNP associated with cancer prior to adjustment for multiple comparisons, rs11089328 (DGCR8), was associated with altered levels of hsa-miR-645 in differential tissue under the dominant model. Three SNPs, rs2740349 (GEMIN4) in carcinoma tissue, and rs235768 (BMP2) and rs2059691 (PRKRA) in normal mucosa, were significantly associated with altered mRNA expression levels across genotypes after multiple comparison adjustment. Rs2740349 (GEMIN4) and rs235768 (BMP2) were significantly associated with the upregulation of six and nine individual miRNAs in normal colonic mucosa, respectively.Our data suggest that few of the SNPs in biogenesis genes we evaluated alter levels of mRNA transcription or colon cancer risk. As only one SNP both alters colon cancer risk and miRNA expression it is likely that SNPs influencing cancer do not do so through miRNAs. Because the significant SNPs were associated with downregulated mRNAs and upregulated miRNAs, and because each SNP was associated with unique miRNAs, it is possible that other mechanisms influence mature miRNA levels.

Project description:BackgroundCardiovascular diseases (CVDs) are associated with an unhealthy lifestyle, including poor diet. Indices reflecting the overall quality of diets are more effective than single food or nutrient-based approaches in clarifying the diet disease relationship. The present study aims to use latent variable modeling to examine the longitudinal joint relationships between the latent profiles of CVDs risk factors and the diet quality index (DQI).MethodsA total of 4390 Iranian adults aged 35 and older within the framework of the Isfahan Cohort Study were included in the current secondary analysis. DQI focused on food groups, including fast foods, sweets, vegetables, fruits, fats, and proteins, based on a validated food frequency questionnaire. The score of DQI has a range between 0 (indicating healthy and high diet quality) and 2 (indicating unhealthy and low diet quality). Blood pressure (BP), anthropometric measurements, blood glucose, serum lipids, and high-sensitivity C-Reactive Protein (hs-CRP) were measured according to standard protocols in 2001, 2007, and 2013 to evaluate the profiles of CVDs risk factors. A Bayesian Multidimensional Graded Responses Linear Mixed Model was used for data analysis.ResultsAt baseline, the participants' mean ± standard deviation age was 50.09 ± 11.21, and 49.5% of them were male. Three latent profiles of CVDs risk factors were derived: (1) Fit Pre-Metabolic Syndrome (FPMS) profile characterized by normal anthropometric indices and some impaired metabolic risk factors; (2) DysLipoproteinemia Central Obese (DLCO) profile with abdominal obesity and impaired low-density lipoprotein cholesterol as well as other normal risk factors; (3) Impaired Laboratory Inflammatory State (ILIS) profile with impaired high-density lipoprotein cholesterol and hs-CRP and other normal risk factors. In general, higher scores of the extracted latent profiles indicated more impaired function in the related risk factors. After controlling for various potential fixed and time-varying confounding variables, a significant positive longitudinal association was found between FPMS, DLCO, and ILIS profiles and DQI (β (95% CrI): 0.26 (0.03,0.51), 0.14 (0.01,0.27), and 0.24 (0.11,0.38), respectively), demonstrating that lower overall diet quality was associated with more impaired function of the related risk factors.ConclusionsMore adherence to a healthy quality diet is associated with lower levels of all emerging latent profiles of CVDs risk factors. Increasing the knowledge of the community about the importance of the quality of consumed foods may help to prevent CVDs. It is recommended that further investigations, particularly interventional studies, be conducted to confirm our results.

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Redefining high-risk patients with stage II colon cancer by risk index and microRNA-21: results from a population-based cohort.

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