Ovarian cancer is the leading cause of death from gynaecological malignancies worldwide. Here we perform a three-stage genome-wide association study (GWAS) in Han Chinese women to identify risk genetic variants for epithelial ovarian cancer (EOC). We scan 900,015 single-nucleotide polymorphisms (SNPs) in 1,057 EOC cases and 1,191 controls in stage I, and replicate 41 SNPs (P meta o10 À 4 ) in 960 EOC cases and 1,799 controls (stage II), and an additional 492 EOC cases and 1,004 controls (stage III). Finally, we identify two EOC susceptibility loci at 9q22.33 (rs1413299 in COL15A1, P meta ¼ 1.88 Â 10 À 8 ) and 10p11.21 (rs1192691 near ANKRD30A, P meta ¼ 2.62 Â 10 À 8 ), and two consistently replicated loci at 12q14.2 (rs11175194 in SRGAP1, P meta ¼ 1.14 Â 10 À 7 ) and 9q34.2 (rs633862 near ABO and SURF6, P meta ¼ 8.57 Â 10 À 7 ) (Po0.05 in all three stages). These results may advance our understanding of genetic susceptibility to EOC.
Extracellular vesicles (EVs) have the potential to be
utilized
as disease-specific biomarkers. Although strategies for on-chip isolation
and detection of EVs have recently been developed, they need preprocessing
of clinical samples and are not accurate enough for disease diagnosis
just judging by EVs concentration. Here, we designed an integrated
microfluidic device named a plasma separation and EV detection (PS-ED)
chip for plasma separation, quantification, and high-throughput protein
analysis of EVs directly from clinical whole blood samples. The device
included two modules (PS and ED module): the PS module was a six-loop
microchannel for rapid separation of plasma from clinical whole blood
samples under inertial force; the amount of EVs in the separated plasma
kept the same value as in the initial blood samples. The module reduced
the mechanical damage to the blood cells and thus reduced the interference
of debris or cellular contents from damaged cells during EVs detection;
the ED module contained four S-channels for quantification and high-throughput
protein analysis of EVs; a wide detection range from 2.5 × 102 to 2.5 × 108 particles/μL with a detection
limit of 95 particles/μL was obtained. Through simultanously
monitoring three proteins (CD81, CD24, and EpCAM) of EVs, the cancer
type can be accurately confirmed. Furthermore, clinical blood sample
analysis verified that the proposed device could be used for accurate
diagnosis and therapy monitoring of ovarian cancer.
Highlights d Levels of NAD+ and NAMPT are decreased in TILs compared to those of other T cells d Tubby is a transcriptional factor for NAMPT in T cells d NAMPT-mediated NAD+ production is essential for T cell activation by generating ATP d NAD+ supplementation enhances the tumor-killing function of T cells
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