No abstract

Cancer is a complex disease with interactions between normal and neoplastic cells. Since current therapies for cancer largely rely on drugs or radiation that kill dividing cells or block cell division, these treatments may have severe side effects on normal proliferating cells in patients with cancer. Recently, immunotherapeutic approaches for cancer therapy, by which monoclonal antibodies (Mabs) target tumor specific antigens, have shown great potential. Glycoprotein non-metastatic melanoma protein B (Gpnmb)/Osteoactivin (OA) is a transmembrane glycoprotein highly expressed in various types of cancer. Gpnmb/OA promotes the migration, invasion and metastasis of tumor cells. CR 011-vcMMAE is a Mab-drug conjugate being developed for the treatment of Gpnmb/OA-expressing cancers. Gpnmb/OA represents an attractive target in cancer immunotherapy and CR011-vcMMAE holds promise as a reagent in targeted therapy for Gpnmb/OA-expressing malignancies.

Background/Aims: There is an increasing risk of end-stage renal disease (ESRD) among Asian people with immunoglobulin A nephropathy (IgAN). A computer-aided system for ESRD prediction in Asian IgAN patients has not been well studied. Methods: We retrospectively reviewed biopsy-proven IgAN patients treated at the Department of Nephrology of the Second Xiangya Hospital from January 2009 to November 2013. Demographic and clinicopathological data were obtained within 1 month of renal biopsy. A random forest (RF) model was employed to predict the ESRD status in IgAN patients. All cases were initially trained and validated, taking advantage of the out-of-bagging(OOB) error. Predictors used in the model were selected according to the Gini impurity index in the RF model and verified by logistic regression analysis. The area under the receiver operating characteristic(ROC) curve (AUC) and F-measure were used to evaluate the RF model. Results: A total of 262 IgAN patients were enrolled in this study with a median follow-up time of 4.66 years. The importance rankings of predictors of ESRD in the RF model were first obtained, indicating some of the most important predictors. Logistic regression also showed that these factors were statistically associated with ESRD status. We first trained an initial RF model using gender, age, hypertension, serum creatinine, 24-hour proteinuria and histological grading suggested by the Clinical Decision Support System for IgAN (CDSS, www.IgAN.net). This 6-predictor model achieved a F-measure of 0.8 and an AUC of 92.57%. By adding Oxford-MEST scores, this model outperformed the initial model with an improved AUC (96.1%) and F-measure (0.823). When C3 staining was incorporated, the AUC was 97.29% and F-measure increased to 0.83. Adding the estimated glomerular filtration rate (eGFR) improved the AUC to 95.45%. We also observed improved performance of the model with additional inputs of blood urea nitrogen (BUN), uric acid, hemoglobin and albumin. Conclusion: In addition to the predictors in the CDSS, Oxford-MEST scores, C3 staining and eGFR conveyed additional information for ESRD prediction in Chinese IgAN patients using a RF model.