Non-diabetic glomerular lesions in diabetic kidney disease: clinical predictors and outcome in an Eastern European cohort
INTERNATIONAL UROLOGY AND NEPHROLOGY
Authors: Popa, Otilia; Stefan, Gabriel; Capusa, Cristina; Mandache, Eugen; Stancu, Simona; Petre, Nicoleta; Mircescu, Gabriel
Abstract
Purpose Since patients' prognosis depends on the lesions identified by kidney biopsy (KB), we aimed to evaluate predictors of non-diabetic kidney disease (NDKD) in diabetic subjects and to assess their kidney outcome as compared to diabetic nephropathy (DN). Methods 180 adults diagnosed by KB with DN (n = 120) or NDKD (n = 60), over a 10 year time-span, were retrospectively included and followed for a mean of 48.1 (95% CI 43.1-53.1) months. Patients with superimposed specific lesions over DN and with steroid-induced diabetes were excluded. The primary endpoint was renal replacement therapy (RRT) initiation. Only subjects who were alive at the end of follow-up (73 with DN and 38 with NDKD) entered the kidney survival analysis. Results Membranous nephropathy (9%) was the most common NDKD. Predictors for NDKD were shorter duration of diabetes (OR 0.88; 95% CI 0.81-0.96, p = 0.004), absence of diabetic retinopathy (OR 0.08; 95% CI 0.01-0.44, p = 0.003), and nephrotic syndrome at presentation (OR 3.55; 95% CI 1.39-9.04, p = 0.008). Subjects with NDKD needed RRT later as those with DN [82 (95% CI 67-97.1) vs. 45 (95% CI 34-56.5) months, p = 0.001]. In an adjusted Cox model, biopsy diagnosed DN independently predicted RRT (OR 4.43; 95% CI 1.54-12.7, p = 0.006). Other predictors were lower eGFR, higher proteinuria, and absence of renin-angiotensin inhibitor therapy. Conclusion As one-third of the investigated subjects had NDKD, and NDKD was associated with a better kidney survival, independently predicted by the type of glomerular lesion, KB appears the most reliable tool to guide therapy and to assess outcome in patients with diabetic kidney disease.
A fusion of CD63-BCAR4 identified in lung adenocarcinoma promotes tumorigenicity and metastasis
BRITISH JOURNAL OF CANCER
Authors: Bae, Kieun; Kim, Jin Hee; Jung, Hyojik; Kong, Sun-Young; Kim, Yun-Hee; Kim, Sunshin; Lee, Geon Kook; Lee, Jin Soo; Lee, Jake June-Koo; Ju, Young Seok; Choi, Yang-Kyu; Yoon, Kyong-Ah
Abstract
Background Recently, fusion variants of the breast cancer anti-oestrogen-resistance 4 (BCAR4) gene were recurrently discovered in lung adenocarcinoma from the genome-wide studies. However, the functional characterisation of BCAR4 fusion has not been investigated. Methods Based on the analysis of RNA-sequencing data, we identified a fusion transcript of CD63-BCAR4 in a Korean patient with lung adenocarcinoma who did not harbour any known activating mutations in EGFR and KRAS genes. To investigate the oncogenic effect of CD63-BCAR4, in vitro and in vivo animal experiments were performed. Results In vitro experiments showed strongly enhanced cell migration and proliferation by the exogenous expression of CD63-BCAR4 protein in bronchial epithelial cells. Cell migration was notably reduced after knockdown of BCAR4 fusion by small-interfering RNA. The tumorigenic and metastatic capability of the CD63-BCAR4 fusion was confirmed by using the mouse xenograft model. Fusion-overexpressed cells result in metastasis to the liver and lung as well as the primary tumours after subcutaneous injection into mice. Cyclin D1, MMP1, Slug and mesenchymal markers were significantly increased after CD63-BCAR4 overexpression in the in vitro and in vivo experiments. Conclusions Taken together, our results suggest a newly identified fusion gene, CD63-BCAR4 as a potential novel oncogene in lung adenocarcinoma.
COA
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