Identification of Novel Phenotypes Correlated with CKD: A Phenotype-Wide Association Study.

Background: A comprehensive understanding of phenotypes related to CKD will facilitate the identification and management of CKD. We aimed to panoramically test and validate associations between multiple phenotypes and CKD using a phenotype-wide association study (PheWAS). Methods: 15,815 subjects from cross-sectional cohorts of the National Health and Nutrition Examination Survey (1999-2006) were randomly 50:50 split into training and testing sets. CKD was defined as eGFR < 60 mL/min/1.73m2. We performed logistic regression analyses between each of 985 phenotypes with CKD in the training set (false discovery rate < 1%) and validated in the testing set (false discovery rate < 1% ). Random forest (RF) model, Nagelkerke's Pseudo-R2, and the area under the receiver operating characteristic (AUROC) were used to validate the identified phenotypes. Results: We identified 18 phenotypes significantly related to CKD, among which retinol, red cell distribution width (RDW), and C-peptide were less researched. The top 5 identified phenotypes were blood urea nitrogen (BUN), homocysteine (HCY), retinol, parathyroid hormone (PTH), and osmolality in RF importance ranking. Besides, BUN, HCY, PTH, retinol, and uric acid were the most important phenotypes based on Pseudo-R2. AUROC of the RF model was 0.951 (full model) and 0.914 (top 5 phenotypes). Conclusion: Our study demonstrated associations between multiple phenotypes with CKD from a holistic view, including 3 novel phenotypes: retinol, RDW, and C-peptide. Our findings provided valid evidence for the identification of novel biomarkers for CKD.

BZW1 promotes cell proliferation in prostate cancer by regulating TGF-ß1/Smad pathway.

Recently, basic leucine zipper and the W2 domain-containing protein 1 (BZW1) are reported to be implicated in tumor progression. However, the role of BZW1 in prostate cancer remains unknown. This study is aimed to investigate the expression of BZW1 and its influence on cell proliferation in prostate cancer. Then, the expression levels of BZW1 were measured in 136 cases of prostate cancer and matched adjacent non-cancerous prostate tissues by quantificational real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The effect of BZW1 on cell proliferation was further explored. QRT-PCR analysis showed that the mRNA levels of BZW1 in prostate cancer were significantly greater compared with those in matched adjacent non-cancerous prostate tissues (P< 0.001). IHC results showed that the high-expression rates of BZW1 in prostate cancer and matched adjacent non-cancerous prostate tissues were 68.4% and 32.4%, and the difference was statistically significant (P< 0.001). BZW1 high expression significantly correlated with T stage, lymph node metastasis, prostate-specific antigen (PSA) and Gleason score (P< 0.05). Patients with BZW1 high expression presented unfavorable prognosis compared with those with BZW1 low expression (P= 0.002). In addition, CCK-8 and colony formation assays revealed that BZW1 overexpression significantly promoted cell proliferation in vitro. Tumor xenograft has shown that BZW1 knockdown significantly inhibited tumor growth in vivo. Moreover, BZW1 overexpression activated the TGF-ß1/Smad1/Smad3 pathway. Therefore, these data indicate that BZW1 overexpression predicts poorer prognosis and promotes cell proliferation in prostate cancer by regulating TGF-ß1/Smad pathway.