BackgroundColorectal cancer (CRC) remains one of the major cancer types and cancer
related death worldwide. Sensitive, non-invasive biomarkers that can
facilitate disease detection, staging and prediction of therapeutic outcome
are highly desirable to improve survival rate and help to determine
optimized treatment for CRC. The small non-coding RNAs, microRNAs (miRNAs),
have recently been identified as critical regulators for various diseases
including cancer and may represent a novel class of cancer biomarkers. The
purpose of this study was to identify and validate circulating microRNAs in
human plasma for use as such biomarkers in colon cancer.Methodology/Principal FindingsBy using quantitative reverse transcription-polymerase chain reaction, we
found that circulating miR-141 was significantly associated with stage IV
colon cancer in a cohort of 102 plasma samples. Receiver operating
characteristic (ROC) analysis was used to evaluate the sensitivity and
specificity of candidate plasma microRNA markers. We observed that
combination of miR-141 and carcinoembryonic antigen (CEA), a widely used
marker for CRC, further improved the accuracy of detection. These findings
were validated in an independent cohort of 156 plasma samples collected at
Tianjin, China. Furthermore, our analysis showed that high levels of plasma
miR-141 predicted poor survival in both cohorts and that miR-141 was an
independent prognostic factor for advanced colon cancer.Conclusions/SignificanceWe propose that plasma miR-141 may represent a novel biomarker that
complements CEA in detecting colon cancer with distant metastasis and that
high levels of miR-141 in plasma were associated with poor prognosis.
Summary
Integrated genomic analyses revealed a miRNA-regulatory network, which further defined a robust integrated mesenchymal subtype associated with poor overall survival in 459 cases of serous ovarian cancer (OvCa) from The Cancer Genome Atlas and 560 cases from independent cohorts. Eight key miRNAs, including miR-506, miR-141 and miR-200a, were predicted to regulate 89% of the targets in this network. Follow-up functional experiments illustrate that miR-506 augmented E-cadherin expression, inhibited cell migration and invasion, and prevented TGFβ-induced epithelial-mesenchymal transition (EMT) by targeting SNAI2, a transcriptional repressor of E-cadherin. In human OvCa, miR-506 expression was correlated with decreased SNAI2 and VIM, elevated E-cadherin, and beneficial prognosis. Nanoparticle delivery of miR-506 in orthotopic OvCa mouse models led to E-cadherin induction and reduced tumor growth.
To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan, and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10-6) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10-18), 6q22.2 (rs9387478, P = 4.14 × 10-10) and 6p21.32 (rs2395185, P = 9.51 × 10-9). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.
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