ABSTRACT
Background: Clear cell renal cell carcinoma (ccRCC) is the main component of renal cell carcinoma (RCC), and advanced ccRCC frequently indicates a poor prognosis. The significance of the CCCH-type zinc finger (CTZF) gene in cancer has been increasingly demonstrated during the past few years. According to studies, targeted radical therapy for cancer treatment may be a revolutionary therapeutic approach. Both lncRNAs and CCCH-type zinc finger genes are essential in ccRCC. However, the predictive role of long non-coding RNA (lncRNA) associated with the CCCH-type zinc finger gene in ccRCC needs further elucidation. This study aims to predict patient prognosis and investigate the immunological profile of ccRCC patients using CCCH-type zinc finger-associated lncRNAs (CTZFLs). Methods: From the Cancer Genome Atlas database, RNA-seq and corresponding clinical and prognostic data of ccRCC patients were downloaded. Univariate and multivariate Cox regression analyses were conducted to acquire CTZFLs for constructing prediction models. The risk model was verified using receiver operating characteristic curve analysis. The Kaplan-Meier method was used to analyze the overall survival (OS) of high-risk and low-risk groups. Multivariate Cox and stratified analyses were used to assess the prognostic value of the predictive feature in the entire cohort and different subgroups. In addition, the relationship between risk scores, immunological status, and treatment response was studied. Results: We constructed a signature consisting of eight CTZFLs (LINC02100, AC002451.1, DBH-AS1, AC105105.3, AL357140.2, LINC00460, DLGAP1-AS2, AL162377.1). The results demonstrated that the prognosis of ccRCC patients was independently predicted by CTZFLs signature and that the prognosis of high-risk groups was poorer than that of the lower group. CTZFLs markers had the highest diagnostic adequacy compared to single clinicopathologic factors, and their AUC (area under the receiver operating characteristic curve) was 0.806. The overall survival of high-risk groups was shorter than that of low-risk groups when patients were divided into groups based on several clinicopathologic factors. There were substantial differences in immunological function, immune cell score, and immune checkpoint expression between high- and low-risk groups. Additionally, Four agents, including ABT737, WIKI4, afuresertib, and GNE 317, were more sensitive in the high-risk group. Conclusion: The Eight-CTZFLs prognostic signature may be a helpful prognostic indicator and may help with medication selection for clear cell renal cell carcinoma.
ABSTRACT
Antibody drugs have been rapidly developed to cure many diseases including COVID-19 infection. Silicone oil is commonly used as a lubricant coating material for devices used in the pharmaceutical industry to store and administer antibody drug formulations. However, the interaction between silicone oil and antibody molecules could lead to the adsorption, denaturation, and aggregation of antibody molecules, impacting the efficacy of antibody drugs. Here, we studied the molecular interactions between antibodies and silicone oil in situ in real time. The effect of the surfactant on such interactions was also investigated. Specifically, the adsorption dynamics of a bispecific antibody (BsAb) onto a silicone oil surface without and with different concentrations of the surfactant PS80 in antibody solutions were monitored. Also the possible lowest effective PS80 concentrations that can prevent the adsorption of BsAb as well as a monoclonal antibody (mAb) onto silicone oil were measured. It was found that different concentrations of PS80 are required for preventing the adsorption of different antibodies. Both BsAB and mAB denature on silicone oil without a surfactant. However, for a low surfactant concentration in the solution, although the surfactant could not completely prevent the antibody from adsorption, it could maintain the native structures of adsorbed BsAb and mAb antibodies on silicone oil. This is important knowledge, showing that to prevent antibody aggregation on silicone oil it is not necessary to add surfactant to a concentration high enough to completely minimize protein adsorption.