Identification of a differentiation-related prognostic nomogram based on single-cell RNA sequencing in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is a kidney cancer that is originated from the lined proximal convoluted tubule, and its major histological subtype is clear cell RCC (ccRCC). This study aimed to retrospectively analyze single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, to explore the correlation among the evolution of tumor microenvironment (TME), clinical outcomes, and potential immunotherapeutic responses in combination with bulk RNA-seq data from The Cancer Genome Atlas (TCGA) database, and to construct a differentiation-related genes (DRG)-based prognostic risk signature (PRS) and a nomogram to predict the prognosis of ccRCC patients. First, scRNA-seq data of ccRCC samples were systematically analyzed, and three subsets with distinct differentiation trajectories were identified. Then, ccRCC samples from TCGA database were divided into four DRG-based molecular subtypes, and it was revealed that the molecular subtypes were significantly correlated with prognosis, clinicopathological features, TME, and the expression levels of immune checkpoint genes (ICGs). A DRG-based PRS was constructed, and it was an independent prognostic factor, which could well predict the prognosis of ccRCC patients. Finally, we constructed a prognostic nomogram based on the PRS and clinicopathological characteristics, which exhibited a high accuracy and a robust predictive performance. This study highlighted the significance of trajectory differentiation of ccRCC cells and TME evolution in predicting clinical outcomes and potential immunotherapeutic responses of ccRCC patients, and the nomogram provided an intuitive and accurate method for predicting the prognosis of such patients.

IGLL5 is correlated with tumor-infiltrating immune cells in clear cell renal cell carcinoma.

Renal cell carcinomas (RCCs) account for about 90% of renal tumors, and their major histological subtype is ccRCC (clear cell RCC). Increasing evidence has indicated that the tumor microenvironment plays a significant role in the occurrence and development of ccRCC. In this study, we used ESTIMATE and CIBERSORT computational methods to calculate the proportion of immune and stromal components and the rate of TICs (tumor-infiltrating immune cells) in 539 ccRCC samples from The Cancer Genome Atlas database. By examining the intersection of the differentially expressed genes obtained by the protein-protein interaction network and Cox regression analysis, we identified only one overlapping gene: IGLL5 (immunoglobulin lambda-like polypeptide 5). We report that IGLL5 expression is correlated with TICs. Furthermore, our immunoinfiltration analyses revealed that three types of TIC are positively correlated with IGLL5 expression. IGLL5 may have potential as a prognostic biomarker of ccRCC.

Monoclonal antibody: the corner stone of modern biotherapeutics.

Worldwide sales of biologic drugs exceeded 100 billion USD in 2011. About 32% is from therapeutic monoclonal antibody (mAb). With many blockbuster biopharmaceutical patents expiring over the next decade, there is a great opportunity for biosimilar to enter the worldwide especially emerging market. Both European Medicines Agency (EMA) and Food and Drug Administration (FDA) have introduced regulatory frameworks for the potential approval of biosimilar mAb therapeutics. Rather than providing a highly abbreviated path, as in the case for small molecule chemical drug, approval for biosimilar mAb will require clinical trial and the details will be very much on a case-by-case basis. Since mAb is the dominant category of biologic drugs, mAb will be the focus of this review. First, the United States (US) and European Union (EU) approved mAb and those in phase 3 trials will be reviewed, then strategies on how to win biosimilar competition will be reviewed.