Search

Background: Kidney renal clear cell carcinoma (KIRC) is an inflammation-related carcinoma, and inflammation has been recognized as an important factor in inducing carcinogenesis. To further explore the role of inflammation in KIRC, we developed an inflammation-related signature and verified its correlation with the tumor micro-environment.Methods: After the differential inflammation-related prognostic genes were screened by Lasso regression, the inflammation-related signature (IRS) was constructed based on the risk score of multivariate Cox regression. Then, the prognostic value of the IRS was evaluated by Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis and multivariate Cox regression. Gene set variation analysis (GSVA) was applied to screen out enriched signaling pathways. Infiltrated immune cells, tumor mutational burden (TMB) and immune checkpoints were explored by CIBERSORTx and maftool.Results: Four genes (TIMP1, PLAUR, CCL22, and IL15RA) were used to construct the IRS in patients with KIRC. Kaplan-Meier analysis and multivariate Cox regression identified that the IRS could independently predict the prognosis of patients with KIRC in the training and validation groups. The diagnostic value of the nomogram increased from 0.811 to 0.845 after adding the IRS to the multiparameter ROC analysis. The GSVA results indicated that IRS was closely related to primary immunodeficiency and antigen processing and presentation. The immune checkpoint LAG3 was highly expressed in patients with high-risk score (p < 0.05), while CD274 (PD-L1) and HAVCR2 were highly expressed in patients with low-risk score (p < 0.001). There was a significant positive correlation between the high-risk score group and CD8+ T, activated CD4+ memory T, gamma and delta regulatory T and M0 macrophage cells, while the low-risk score group was negatively associated with B memory, plasma, resting CD4+ memory T, activated NK, M1 macrophages and resting mast cells.Conclusion: We found that the IRS might serve as a biomarker to predict the survival of KIRC. Moreover, patients with high or low-risk score might be sensitive to immune drugs at different immune checkpoints.

IntroductionExisting behavioral and neuroimaging studies revealed inter-individual variability in the selection of the two phonological routes in word reading. However, it is not clear how individuals’ preferred reading pathways/strategies modulate the involvement of a certain brain region for phonological learning in a new language, and consequently affect their behavioral performance on phonological access.MethodsTo address this question, the present study recruited a group of native Chinese speakers to learn two sets of artificial language characters, respectively, in addressed-phonology training (i.e., whole-word mapping) and assembled-phonology training conditions (i.e., grapheme-to-phoneme mapping).ResultsBehavioral results showed that the more lexical pathways participants preferred, the better they performed on newly-acquired addressed characters relative to assembled characters. More importantly, neuroimaging results showed that participants who preferred lexical pathway in phonological access show less involvement of brain regions for addressed phonology (e.g., the bilateral orbitofrontal cortex and right pars triangularis) in the processing of newly-acquired addressed characters.ConclusionThese results indicated that phonological access via the preferred pathway required less neural resources to achieve better behavioral performance. These above results provide direct neuroimaging evidence for the influence of reading pathway preference on phonological learning.