Potential mechanisms and drug prediction of Rheumatoid Arthritis and primary Sjögren’s Syndrome: A public databases-based study

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(2), P. e0298447 - e0298447

Published: Feb. 15, 2024

Rheumatoid arthritis (RA) and primary Sjögren’s syndrome (pSS) are the most common systemic autoimmune diseases, they increasingly being recognized as occurring in same patient population. These two diseases share several clinical features laboratory parameters, but exact mechanism of their co-pathogenesis remains unclear. The intention this study was to investigate molecular mechanisms involved RA pSS using integrated bioinformatic analysis. RNA-seq data for were picked up from Gene Expression Omnibus (GEO) database. Co-expression genes linked with weighted gene co-expression network analysis (WGCNA) differentially expressed (DEG) Then, we screened public disease–gene interaction databases (GeneCards Comparative Toxicogenomics Database) targets associated pSS. DGIdb database used predict therapeutic drugs Human microRNA Disease Database (HMDD) screen out microRNAs Finally, a miRNA–gene created Cytoscape. Four hub ( CXCL10 , GZMA ITGA4 PSMB9 ) obtained intersection WGCNA, differential databases. Twenty-four corresponding predicted Among 24 drugs, five had already been reported treatment Other such bortezomib, carfilzomib, oprozomib, cyclosporine zidovudine, may be ideal future patients According network, hsa-mir-21 play significant role shared by In conclusion, identified commom potential biomarkers publicly available based on targets. A new understanding is provided according network.

Language: Английский

POLE -related gene signature predicts prognosis, immune feature, and drug therapy in human endometrioid carcinoma

Heliyon, Journal Year: 2024, Volume and Issue: 10(8), P. e29548 - e29548

Published: April 1, 2024

The POLE subtype of Endometrial carcinoma (EC) is linked to a favourable prognosis in the molecular classification. We proposed ascertain potential connection between and improved prognosis. In order forecast prognosis, least absolute shrinkage selection operator (LASSO) Cox regression analysis weighted gene co-expression network (WGCNA) were employed, POLE-related risk signature (PRS) model was developed validated. Single-sample set enrichment (ssGSEA) with "GSVA" package employed analyse immunity characteristics. Drug susceptibility studies conducted compare half-maximal inhibitory concentration (IC50) medicines high- low-risk groups. PRS generated employing LASSO coefficients ELF1, MMADHC, AL021707.6 genes. Our study demonstrated that score tumour stage, grade, survival. Furthermore, group possessed elevated levels expression connected immunological checkpoints HLA. outcomes emerged might have value identifying patients good facilitating personalised treatment clinic.

Language: Английский

Effective treatment strategies and key factors influencing therapeutic efficacy in advanced SMARCA4-deficient non-small cell lung cancer

Lung Cancer, Journal Year: 2024, Volume and Issue: 198, P. 108022 - 108022

Published: Nov. 9, 2024

Highlights•First-line local treatment combined with immunotherapy is associated a lower risk of disease progression in locally advanced SMARCA4-deficient NSCLC.•First-line improves survival metastatic NSCLC.•STK11/KEAP1 mutations are linked to reduced efficacy NSCLC.AbstractIntroductionSMARCA4/BRG1-deficient non-small cell lung cancer (SD-NSCLC) high invasiveness and poor prognosis primary resistance standard treatment, especially late-stage patients. This study aimed explore effective treatments identify critical factors impacting therapeutic enhance outcomes for SD-NSCLC patients.Methods103 patients stage III/IV diagnosed by immunohistochemistry from May 2019 March 2024 were included this study. We assessed the patients' clinical genetic features, analyzed according TNM stage, further evaluated efficacy.ResultsIn III patients, no significant differences median progression-free (mPFS) overall (mOS) observed between receiving at site those who did not (p > 0.05), while adding ICIs (immune checkpoint inhibitors) significantly improved mPFS compared non-ICIs (15.0 vs. 7.7 months, p = 0.033), though mOS 0.05). For IV (8.9 4.2 0.006) (19.7 13.1 0.007) treatments. However, among ICIs-treated addition lesion affect Patients STK11/KEAP1 had shorter (3.6 16.2 0.001) (17.7 31.3 0.002), difference was different tumor mutation burden (TMB) PD-L1 expression levels.ConclusionICIs shows promising results SD-NSCLC, first-line SD-NSCLC. may be immunotherapy.

Language: Английский