Additional file 2: of MicroRNAs as markers of progression in cervical cancer: a systematic review

Table S1. Dysregulated miRNAs in ICC progression in multiple studies as retrieved from the reviewed literature. Table S2. Validated target genes for the dysregulated miRNAs in ICC progression in multiple studies (data retrieved from miRWalk2.0). Table S3. Enrichment analysis for validated target genes of miRNA down-regulated in ICC progression (Kegg Pathways). Table S4. A group of 5 up-regulated miRNAs retrieved by multiple studies in the present review. Table S5. Enrichment analyses for genes targeted (n= 2620) by the above 5 miRNAs up-regulated in ICC progression (Kegg Pathways). Table S6. Enrichment analyses for genes targeted (n= 2620) by the above 5 miRNAs up-regulated in ICC progression (Virus Mint). Table S7. Altered expression levels of genes relevant for ICC (reported in CCDB) targeted by dysregulated miRNAs in ICC progression. (DOCX 39 kb

Additional file 1: of MicroRNAs as markers of progression in cervical cancer: a systematic review

Figure S1. Workflow of selection of the studies included in the present Review. (TIF 1519 kb

Single Nucleotide Polymorphisms within Interferon Signaling Pathway Genes Are Associated with Colorectal Cancer Susceptibility and Survival

<div><p>Interferon (IFN) signaling has been suggested to play an important role in colorectal carcinogenesis. Our study aimed to examine potentially functional genetic variants in interferon regulatory factor 3 (<i>IRF3</i>), <i>IRF5</i>, <i>IRF7</i>, type I and type II <i>IFN</i> and their receptor genes with respect to colorectal cancer (CRC) risk and clinical outcome. Altogether 74 single nucleotide polymorphisms (SNPs) were covered by the 34 SNPs genotyped in a hospital-based case-control study of 1327 CRC cases and 758 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 483 patients. Seven SNPs in <i>IFNA1</i>, <i>IFNA13</i>, <i>IFNA21</i>, <i>IFNK</i>, <i>IFNAR1</i> and <i>IFNGR1</i> were associated with CRC risk. After multiple testing correction, the associations with the SNPs rs2856968 (<i>IFNAR1</i>) and rs2234711 (<i>IFNGR1</i>) remained formally significant (<i>P</i> = 0.0015 and <i>P</i><0.0001, respectively). Multivariable survival analyses showed that the SNP rs6475526 (<i>IFNA7/IFNA14</i>) was associated with overall survival of the patients (<i>P</i> = 0.041 and event-free survival among patients without distant metastasis at the time of diagnosis, <i>P</i> = 0.034). The hazard ratios (HRs) for rs6475526 remained statistically significant even after adjustment for age, gender, grade and stage (<i>P</i> = 0.029 and <i>P</i> = 0.036, respectively), suggesting that rs6475526 is an independent prognostic marker for CRC. Our data suggest that genetic variation in the IFN signaling pathway genes may play a role in the etiology and survival of CRC and further studies are warranted.</p></div

Characteristics of the 483 newly diagnosed Czech colorectal cancer patients.

<p>No., number of patients; T, size or direct extent of the primary tumor; N, degree of spread to regional lymph nodes; M, presence of metastasis.</p><p>Characteristics of the 483 newly diagnosed Czech colorectal cancer patients.</p

Polymorphisms evaluated in this study.

1<p>Minor allele frequency (MAF) based on Utah residents with Northern and Western European ancestry from the CEPH collection in the HapMap project.</p>2<p>Pairwise linkage disequilibrium (r²) was calculated for the SNPs with MAF≥10% within the regions of interest based on Utah residents with Northern and Western European ancestry from the CEPH collection in the HapMap project.</p>3<p>Because no assays were available for the potentially functionally SNPs, the SNPs rs6475526, rs1874327 and rs2856968, respectively, were genotyped instead.</p><p>Polymorphisms evaluated in this study.</p

Kaplan-Meier analysis of survival according to genotypes of SNPs rs6475526, located 5′ to IFNA14, and capturing two IFN7 promoter SNPs and rs7047687 located in IFNA21 promoter.

<p>(A) Overall survival among all colorectal cancer patients (rs6475526, n = 465). (B) Event-free survival among patients without distant metastasis at diagnosis (rs6477526, n = 310). (C) Overall survival among all colorectal cancer patients (rs7047687, n = 464).</p

Associations between candidate SNPs and colorectal cancer susceptibility.

1<p>Number of cases may differ due to missing data.</p>2<p>Two-sided X² test for genotype distribution between the cases and controls, adjusted for age and gender.</p><p>No., number of subjects; OR, odds ratio; CI, confidence interval. Bold numbers indicate a statistical significance at 5% level.</p><p>Bold numbers in Italics indicate a statistical significance at 5% level after adjustment for multiple comparisons.</p><p>Associations between candidate SNPs and colorectal cancer susceptibility.</p

Association of rs7047687, rs6745526 and rs11770589 with overall and event-free survival of newly diagnosed colorectal cancer patients.

1<p>Overall survival was calculated for all patients diagnosed between 2003 and 2010 (n = 483).</p>2<p>Event-free survival was calculated for patients diagnosed between 2003 and 2010, who did not have distant metastasis at the time of diagnosis</p><p>(n = 325).</p>3<p>Number of cases may differ due to missing data.</p><p>No., number of patients; OR, odds ratio; CI, confidence interval; M = 0, no distant metastasis present Bold numbers indicate a statistical significance at 5% level.</p><p>Association of rs7047687, rs6745526 and rs11770589 with overall and event-free survival of newly diagnosed colorectal cancer patients.</p

Genotype and Haplotype Analyses of <i>TP53</i> Gene in Breast Cancer Patients: Association with Risk and Clinical Outcomes

<div><p>Variations in the <i>TP53</i> gene have been suggested to play a role in many cancers, including breast. We previously observed an association between <i>TP53</i> haplotypes based on four polymorphisms (rs17878362, rs1042522, rs12947788, and rs17884306) and the risk of colorectal and pancreatic cancer. Based on these results, in the present study, we have investigated the same polymorphisms and their haplotypes in 705 breast cancer cases and 611 healthy controls in relation to the disease risk, histopathological features of the tumor and clinical outcomes. In comparison to the most common haplotype A₁-G-C-G, all the other identified haplotypes were globally associated with a significantly decreased breast cancer risk (P = 0.006). In particular, the A₂-G-C-G haplotype was associated with a marked decreased risk of breast cancer when compared with the common haplotype (P = 0.0001). Moreover, rs1042522 in patients carrying the GC genotype and receiving only the anthracycline-based chemotherapy was associated with both overall and disease-free survival (recessive model for overall survival HR = 0.30 95% CI 0.11–0.80, P = 0.02 and for disease-free survival HR = 0.42 95% CI 0.21–0.84, P = 0.01). Present results suggest common genetic features in the susceptibility to breast and gastrointestinal cancers in respect to <i>TP53</i> variations. In fact, similar haplotype distributions were observed for breast, colorectal, and pancreatic patients in associations with cancer risk. Rs1042522 polymorphism (even after applying the Dunn-Bonferroni correction for multiple testing) appears to be an independent prognostic marker in breast cancer patients.</p></div

Kaplan-Meier disease-free survival curves for <i>TP53</i> rs17878362 polymorphism in patients receiving only the hormonal therapy (log-rank for recessive model).

<p>Numbers of patients at risk are indicated in the lower part of the plot.</p