Identification and experimental validation of a tumor-infiltrating lymphocytes-related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common aggressive malignant tumor of the urinary system. Given the heterogeneity of the tumor microenvironment, immunotherapy may not fully exert its role in the treatment of advanced patients. Long noncoding RNA (lncRNA) has been reported to be critically associated with the differentiation and maturation of tumor-infiltrating lymphocytes (TILs), which work against tumor cells. In this study, we identified 10 TIL-related lncRNAs (AL590094.1, LINC02027, LINC00460, AC147651.1, AC026401.3, LINC00944, LINC01615, AP000439.2, AL162586.1, and AC084876.1) by Pearson correlation, univariate Cox regression, Lasso regression, and multivariate Cox regression based on The Cancer Genome Atlas (TCGA) database. A risk score model was established based on these lncRNAs. Next, a nomogram was constructed to predict the overall survival. By employing differentially expressed genes (DEGs) between groups with high and low risk scores, gene ontology (GO) enrichment analysis was performed to identify the major biological processes (BP) related to immune DEGs. We analyzed the mutation data of the groups and demonstrated that SETD2 and BAP1 had the highest mutation frequency in the high-risk group. The "CIBERSORT" R package was used to detect the abundance of TILs in the groups. The expression of lymphocyte markers was compared. We also determined the expression of two lncRNAs (AC084876.1 and AC026401.3) and their relationship with lymphocyte markers in the kidney tissue of ccRCC patients and showed that there was a positive correlation between AC084876.1 and FoxP3. Proliferation, migration, and invasion of AC084876.1-downregulated ccRCC cell lines were inhibited, and the expression of PD-L1 and TGF-ß secretion decreased. To our knowledge, this is the first bioinformatics study to establish a prognostic model for ccRCC using TIL-related lncRNAs. These lncRNAs were associated with T-cell activities and may serve as biomarkers of disease prognosis.

Gender difference in association between H-type hypertension and subcortical ischemic vascular disease.

Background: Subcortical ischemic vascular disease (SIVD) is a leading cause of vascular dementia. The present study tries to explore not only the gender-specific association between H-type hypertension and SIVD but also the indirect effects of H-type hypertension on cognition through the ischemic brain injury caused by SIVD. Materials and methods: A total of 601 SIVD patients were included, comprising 322 males and 279 females. H-type hypertension was defined as hypertension accompanied with elevated serum total homocysteine (tHcy) level. The imaging manifestations of ischemic brain injury caused by SIVD were also evaluated, including white matter lesions (WML), lacunar infarction (LI) and brain atrophy (BA). Gender-specific subgroup analyses in association between H-type hypertension and SIVD were conducted, followed by a structural equation model based evaluation of the gender-specific mediating effects of SIVD on the relationship between H-type hypertension and cognition. Results: For males, there was no noticeable difference in WML, LI and BA scores among control group, isolated hypertension group, isolated high tHcy group, and H-type hypertension group in most brain regions, but significant difference was found in all brain regions for females. Multiple regression analyses showed that H-type hypertension was significantly associated with WML, LI and BA for females, but not for males. For males, H-type hypertension mainly affected cognition through direct effect, while the H-type hypertension effect was mediated by ischemic brain injury caused by SIVD for females. Conclusion: H-type hypertension was more closely related to SIVD for females than males, suggesting a gender-specific difference in association patterns between H-type hypertension and cognition.