Transcriptome analysis reveals the prognostic and immune infiltration characteristics of glycolysis and hypoxia in head and neck squamous cell carcinoma

Background This study aims to construct a new prognostic gene signature based on cancer hallmarks for patients with Head and neck squamous cell carcinoma (HNSCC). Method The transcriptome profiling data and hallmark gene sets in the Molecular Signatures Database was used to explore the cancer hallmarks most relevant to the prognosis of HNSCC patients. Differential gene expression analysis, weighted gene co-expression network analysis, univariate COX regression analysis, random forest algorithm and multiple combinatorial screening were used to construct the prognostic gene signature. The predictive ability of gene signature was verified in the TCGA HNSCC cohort as the training set and the GEO HNSCC cohorts (GSE41613 and GSE42743) as the validation sets, respectively. Moreover, the correlations between risk scores and immune infiltration patterns, as well as risk scores and genomic changes were explored. Results A total of 3391 differentially expressed genes in HNSCC were screened. Glycolysis and hypoxia were screened as the main risk factors for OS in HNSCC. Using univariate Cox analysis, 97 prognostic candidates were identified (P<0.05). Top 10 important genes were then screened out by random forest. Using multiple combinatorial screening, a combination with less genes and more significant P value was used to construct the prognostic gene signature (RNF144A, STC1, P4HA1, FMNL3, ANO1, BASP1, MME, PLEKHG2 and DKK1). Kaplan-Meier analysis showed that patients with higher risk scores had worse overall survival (p <0.001). The ROC curve showed that the risk score had a good predictive efficiency (AUC> 0.66). Subsequently, the predictive ability of the risk score was verified in the validation sets. Moreover, the two-factor survival analysis combining the cancer hallmarks and risk scores suggested that HNSCC patients with the high hypoxia or glycolysis & high risk-score showed the worst prognosis. Besides, a nomogram based on the nine-gene signature was established for clinical practice. Furthermore, the risk score was significantly related to tumor immune infiltration profiles and genome changes. Conclusion This nine-gene signature associated with glycolysis and hypoxia can not only be used for prognosis prediction and risk stratification, but also may be a potential therapeutic target for patients with HNSCC.

Reaction behaviour of peptide-based single thiol-thioesters exchange reaction substrate in the presence of externally added thiols

Identification of patterns in chemical reaction pathways aids in the effective design of molecules for specific applications. Here, we report on model reactions with a water-soluble single thiol-thioester exchange (TTE) reaction substrate, which was designed taking in view biological and medical applications. This substrate consists of the thio-depsipeptide, Ac-Pro-Leu-Gly-SLeu-Leu-Gly-NEtSH (TDP) and does not yield foul-smelling thiol exchange products when compared with aromatic thiol containing single TTE substrates. TDP generates an α,ω-dithiol crosslinker in situ in a ‘pseudo intramolecular’ TTE. Competitive intermolecular TTE of TDP with externally added “basic” thiols increased the crosslinker concentration whilst “acidic” thiols decreased its concentration. TDP could potentially enable in situ bioconjugation and crosslinking applications. Graphic abstract The competition between ‘pseudo intramolecular’ and intermolecular exchange of a peptide-based thiol-thioester exchange (TTE) substrate can be used to control the relative amount of final exchange products based on size and pKa values of externally added thiols. Potential application of this system can be seen in the development of TTE substrates for the rapid identification of thiols by dynamic combinatorial screening.

Advanced Continuous-Flow Microfluidic Device for Parallel Screening of Crystal Polymorphs, Morphology and Kinetics at Controlled Supersaturation

A flow-controlled microfluidic device for parallel and combinatorial screening of crystalline materials can profoundly impact the discovery and development of active pharmaceutical ingredients and other crystalline materials. While the existing...