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mRNA vaccines are becoming a feasible alternative for treating cancer. To develop mRNA vaccines against LUAD, potential antigens were identified and LUAD ferroptosis subtypes distinguished for selecting appropriate patients. The genome expression omnibus, cancer genome atlas (TCGA) and FerrDB were used to collect gene expression profiles, clinical information, and the genes involved in ferroptosis, respectively. cBioPortal was used to visualize and compare genetic alterations, GEPIA2 to calculate prognostic factors of the selected antigens, and TIMER to visualize the relationship between potential antigens and tumor immune cell infiltration. Consensus clustering analysis was utilized to identify ferroptosis subtypes and their prognostic value assessed by Log-rank and cox regression tests. The modules of ferroptosis-related gene screening were conducted by weight gene co-expression network analysis. The LUAD ferroptosis landscape was visualized through dimensionality reduction and graph learning. Six tumor antigens had obvious LUAD-mutations, positively correlated with different antigen-presenting cells, and might induce tumor cell ferroptosis. LUAD patients were stratified into three ferroptosis subtypes (FS1, FS2, and FS3) according to diverse molecular, cellular, and clinical characteristics. FS3 showed the highest tumor mutation burden and the most somatic mutations, deemed potential indicators of mRNA vaccine effectiveness. Moreover, different ferroptosis subtypes expressed distinct immune checkpoints and immunogenic cell death modulators. AGPS, NRAS, MTDH, PANX1, NOX4, and PPARD are potentially suitable for mRNA vaccinations against LUAD, specifically in patients with FS3 tumors. This study defines vaccination candidates and establishes a theoretical basis for LUAD mRNA vaccinations. [ABSTRACT FROM AUTHOR]

To compare the effects of aminosalicylic acid, glucocorticoids and immunosuppressants on the expression levels of multidrug resistance genes in patients with ulcerative colitis (UC), with the aim of providing a theoretical and therapeutic basis for the diagnosis, treatment, and prevention of UC. Fresh colonic mucosal tissues or postoperative pathological biopsies from 148 UC patients were collected, and the distribution sites and morphology of P-glycoprotein (P-gp) were detected using immunohistochemical staining. RT-PCR was used to quantify the expression levels of multidrug resistance gene (MDR1) mRNA before and after the corresponding treatment, and the effects of aminosalicylic acid, glucocorticoids and immunosuppressive drugs on P-gp were compared. In addition, the effects of the three drugs on MDR1 mRNA were analyzed. Administration of 5-aminosalicylic acid (5-ASA) drugs did not correlate with MDR1 expression in UC, whereas administration of glucocorticoids and immunosuppressive drugs was positively correlated with MDR1 expression profile. The expression levels of MDR1 mRNA and its product P-gp were significantly upregulated in patients who did not respond to glucocorticoids and immunosuppressive drugs. 5-ASA had no effect on the expression levels of MDR1 and its product P-gp in patients with a confirmed diagnosis of UC. However, the use of glucocorticoids and immunosuppressants can increase the expression level of MDR1. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma (ICC) is a rare but highly aggressive malignant tumor arising within the liver, with a 5-year survival rate of only 20–40% after surgery. The role of interleukin-8 (IL-8) in ICC progression remains elusive. A transcriptomic approach based on IL-8 stimulation first revealed significant upregulation of the prometastatic gene CD97 and key epithelial–mesenchymal transition (EMT) factors E-cadherin and vimentin. Immunohistochemistry of 125 ICC tissues confirmed the positive correlation between IL-8 and CD97. Multivariable Cox regression indicated that they are both independent predictors of ICC prognosis. Mechanistically, IL-8 treatment induced CD97 expression at 50 and 100 ng/ml in QBC-939 and QBE cells, respectively. Moreover, the induction of cell migration and invasion upon IL-8 treatment was attenuated by CD97 RNA interference, and the expression of EMT-associated genes was dramatically inhibited. To determine whether CXCR1 or CXCR2 are downstream effectors of IL-8, siCXCR2 was applied and shown to significantly attenuate the oncogenic effects of IL-8 by inhibiting the phosphorylation of PI3K/AKT. Finally, the induction of CD97 expression by the PI3K pathway was verified by treatment with the inhibitor LY294002. In vivo, the significant tumor growth and lung metastasis effects induced by intraperitoneal injection of IL-8 were greatly inhibited by silencing CD97 in nude mice. Collectively, the study presents a novel mechanism of the IL-8-CXCR2-PI3K/AKT axis in regulating CD97 expression, which leads to ICC metastasis mainly through EMT. The study may provide alternatives for targeting the tumor microenvironment in metastatic ICC. [ABSTRACT FROM AUTHOR]