Characteristics of breast cancer cases and cancer-free controls (Stage I and II).

a<p>Two-sided <i>X</i>² test, <i>P</i>< 0.05 was considered statistically significant.</p>b<p>Due to missing values, the number of patients was <2744 and that of controls was <3125 in the test set</p>c<p>First- and second-degree relatives with history of cancer.</p

miR-485-5p Binding Site SNP rs8752 in <i>HPGD</i> Gene Is Associated with Breast Cancer Risk

<div><p>Background</p><p>Single nucleotide polymorphisms (SNPs) that reside in microRNA target sites may play an important role in breast cancer development and progression. To reveal the association between microRNA target site SNPs and breast cancer risk, we performed a large case-control study in China.</p><p>Methods</p><p>We performed a two-stage case-control study including 2744 breast cancer cases and 3125 controls. In Stage I, we genotyped 192 SNPs within microRNA binding sites identified from the “Patrocles” database using custom Illumina GoldenGate VeraCode assays on the Illumina BeadXpress platform. In Stage II, genotyping was performed on SNPs potentially associated with breast cancer risk using the TaqMan platform in an independent replication set.</p><p>Results</p><p>In stage I, 15 SNPs were identified to be significantly associated with breast cancer risk (P<0.05). In stage II, one SNP rs8752 was replicated at P<0.05. This SNP is located in the 3’ untranslated region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (<i>HPGD</i>) gene at 4q34-35, a miR-485-5p binding site. Compared with the GG genotype, the combined GA+AA genotypes has a significantly higher risk of breast cancer (OR = 1.18; 95% CI: 1.06-1.31, P = 0.002). Specifically, this SNP was associated with estrogen receptor (ER) positive breast cancer (P = 0.0007), but not with ER negative breast cancer (P = 0.23), though p for heterogeneity not significant.</p><p>Conclusion</p><p>Through a systematic case-control study of microRNA binding site SNPs, we identified a new breast cancer risk variant rs8752 in <i>HPGD</i> in Chinese women. Further studies are warranted to investigate the underling mechanism for this association.</p></div

Logistic regression analysis of associations between rs8752 and the risk of breast cancer (Stage I and II).

a<p>ORs were adjusted for age, smoking status, menopause status, oral contraception use, history of benign breast diseases, and family history of cancer.</p

Plasma miRNAs as Diagnostic and Prognostic Biomarkers for Ovarian Cancer

<div><p>Background</p><p>Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC.</p><p>Methodology/Principal Findings</p><p>We evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions. All samples were grouped into screening, training and validation sets. We scanned the circulating plasma miRNAs by TaqMan low-density array in the screening set and identified/validated miRNA markers by real-time polymerase chain reaction assay in the training set. Receiver operating characteristic and logistic regression analyses established the diagnostic miRNA panel, which were confirmed in the validation sets. We found higher plasma miR-205 and lower let-7f expression in cases than in controls. MiR-205 and let-7f together provided high diagnostic accuracy for EOC, especially in patients with stage I disease. The combination of these two miRNAs and carbohydrate antigen-125 (CA-125) further improved the accuracy of detection. MiR-483-5p expression was elevated in stages III and IV compared with in stages I and II, which was consistent with its expression pattern in tumor tissues. Furthermore, lower levels of let-7f were predictive of poor prognosis in EOC patients.</p><p>Conclusions/Significance</p><p>Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis.</p></div

PFS by plasma let-7f level.

<p>(A) A PFS analysis for all patients (n = 360) revealed that lower plasma levels of let-7f were associated with poor prognosis (<i>P</i> = 0.006). Stage-specific Kaplan-Meier survival curves revealed that the <i>P</i> values of the log-rank test were 0.576 and 0.002 for stages I and II (B) and III and IV (C), respectively. The survival data were compared using the log-rank test, and let-7f expression levels in patients were defined as high or low relative to the median. NP, no progression; P, progression.</p

Cox regression analysis of EOC OS and PFS in relation to plasma let-7f levels.

<p>Cox regression analysis of EOC OS and PFS in relation to plasma let-7f levels.</p

Study design flowchart.

<p>We separated the samples into three sets: screening, training, and validation. The validation set included two phases to validate the best panel.</p

Pathological and demographic characteristics of EOC patients in the training and validation sets.

*<p>In phase II, some information was missing for Nanjing Center patients.</p

ROC of the panel (miR-205 and let-7f) for EOC cases.

<p>We established the miR-205 and let-7f panel in validation phase I and confirmed it in independent samples in phase II. In phase I, (A) the AUC was 0.831 (95% CI, 0.772 to 0.880; sensitivity = 62.4%, specificity = 92.9%) for cases; (B) 0.895 (95% CI, 0.822 to 0.967; sensitivity = 77.8%, specificity = 90.0%) for early-stage cases versus controls; and (C) 0.814 (95% CI, 0.700 to 0.929; sensitivity = 68.4%, specificity = 92.9%) for low CA-125 (<35 U/ml) cases versus controls. In phase II, (D) the AUC was 0.813 (95% CI, 0.759 to 0.860; sensitivity = 71.3%, specificity = 82.0%) for cases versus controls; (E) 0.783 (95% CI, 0.699 to 0.853; sensitivity = 70.0%, specificity = 82.0%) for early-stage cases versus controls; and (F) 0.726 (95% CI, 0.634 to 0.805; sensitivity = 64.3%, specificity = 72.0%) for low CA-125 (<35 U/ml) cases versus controls.</p