Proteome atlas of human chromosome 8 and its multiple 8p deficiencies in tumorigenesis of the stomach, colon, and liver.

Chromosome 8, a medium-length euchromatic unit in humans that has an extraordinarily high mutation rate, can be detected not only in evolution but also in multiple mutant diseases, such as tumorigenesis, and further invasion/metastasis. The Chromosome-Centric Human Proteome Project of China systematically profiles the proteomes of three digestive organs (i.e., stomach, colon, and liver) and their corresponding carcinoma tissues/cell lines according to a chromosome organizational roadmap. By rigorous standards, we have identified 271 (38.7%), 330 (47.1%), and 325 (46.4%) of 701 chromosome 8-coded proteins from stomach, colon, and liver samples, respectively, in Swiss-Prot and observed a total coverage rate of up to 58.9% by 413 identified proteins. Using large-scale label-free proteome quantitation, we also found some 8p deficiencies, such as the presence of 8p21-p23 in tumorigenesis of the above-described digestive organs, which is in good agreement with previous reports. To our best knowledge, this is the first study to have verified these 8p deficiencies at the proteome level, complementing genome and transcriptome data.

Cost-effectiveness of olaparib, a PARP inhibitor, for patients with metastatic castration-resistant prostate cancer in China and United States.

Background: Metastatic prostate cancer is initially sensitive to androgen receptor inhibition, but eventually becomes metastatic castration-resistant prostate cancer (mCRPC). Olaparib has longer progression-free survival and better measures of response and patient-reported end points than either enzalutamide or abiraterone. In the present study, 2 Markov models were established to analyze the cost utility of olaparib in treating mCRPC from the perspectives of health services in China and the United States. Methods: Markov models were established to simulate the progress of mCRPC in China and the United States. The state transition probabilities and clinical data were extracted from the PROfound trial. The cost data were estimated from local pricing, the relevant literature and expert consultancy. The health outcomes are expressed by quality-adjusted life years (QALYs). All costs and incremental cost-effectiveness ratios (ICERs) are presented in US dollars. One-way deterministic sensitivity analysis and probabilistic sensitivity analysis were performed to assess the uncertainty of the models. Results: Based on the Chinese Markov model, the base case ICER for olaparib versus the control group was ¥392,727.87, with incremental costs of ¥93,673.23 and an incremental QALY of 0.23, indicating that it was not cost effective from the aspect of the Chinese healthcare system. However, as shown by the American Markov model, olaparib was dominant versus the control group, with a cost saving of $69,675.20 and a gain of 0.23 QALYs. One-way deterministic sensitivity analysis and probabilistic sensitivity analyses showed that the modeling results were not significantly affected by the model parameters. Conclusions: Olaparib treatment in patients with mCRPC is not cost effective in China, but it is cost saving in the United States.