Integrated single-cell and transcriptome sequencing analyses develops a metastasis-based risk score system for prognosis and immunotherapy response in uveal melanoma.

Background: Uveal melanoma (UM) is the most frequent ocular neoplasm with a strong metastatic ability. The prognostic value of metastasis-associated genes (MAGs) of UM remains unclear. It is urgent to develop a prognostic score system according to the MAGs of UM. Methods: Unsupervised clustering was used to identify MAGs-based molecular subtypes. Cox methods were utilized to generate a prognostic score system. The prognostic ability of the score system was detected by plotting ROC and survival curves. The immune activity and underlying function were depicted by CIBERSORT GSEA algorithms. Results: Gene cluster analysis determined two MAGs-based subclusters in UM, which were remarkably different in clinical outcomes. A risk score system containing six MAGs (COL11A1, AREG, TIMP3, ADAM12, PRRX1 and GAS1) was set up. We employed ssGSEA to compare immune activity and immunocyte infiltration between the two risk groups. Notch, JAK/STAT and mTOR pathways were greatly enriched in the high-risk group. Furthermore, we observed that knockdown of AREG could inhibit UM proliferation and metastasis by in vitro assays. Conclusion: The MAGs-based subtype and score system in UM can enhance prognosis assessment, and the core system provides valuable reference for clinical decision-making.

Research progress on serological indices and their clinical application in rheumatoid arthritis.

BACKGROUND: As a chronic systemic autoimmune disease of undetermined etiology, rheumatoid arthritis (RA) has a complex pathogenesis, which involves multiple proteins and cytokines. The 2010 ACR/EULAR classification criteria facilitate early diagnosis of RA with reduced specificity when compared to the 1987 ACR criteria. Hence, it is imperative to identify novel serological inflammatory indicators and targets, in order to explain the complex regulatory network of RA. The present review discusses the associations of various inflammatory factors with RA and its underlying mechanism. Besides, the review also provides a novel insight into the clinical treatment of RA. MATERIALS AND METHODS: According to the PRISMA guidelines, databases like Web of Science, Google-Scholar, Pubmed and Scopus were systematically searched for articles from January 1, 2018 to January 1, 2022 using The following 2 keywords: "rheumatoid arthritis", "Inflammatory cytokines", "ILs", "serum amyloid protein A", "matrix metalloproteinase 3", "RANKL", "Glucose-6-phosphoisomerase", "Anti-keratin antibody", "1,25-Dihydroxyvitamin D3". RESULTS: Indicators like MMPs, ILs, glucose-6-phosphate isomerase (GPI), anti-keratin antibody (AKA) and receptor activator of nuclear factor-κB ligand (RANKL) are the current hotspots in the efficacy research of RA. The present review suggests that ILs are highly expressed in the serum and synovial tissues of RA patients. By targeted inhibition of ILs with inhibitor application, precise RA treatment can be achieved. CONCLUSIONS: Based on these results, it can be concluded that inflammatory factors have certain guiding significance in the diagnosis and efficacy evaluation of RA. However, the mechanisms of interactions among them are rather complex, which deserve further exploration.

miR-221-3p and miR-15b-5p promote cell proliferation and invasion by targeting Axin2 in liver cancer.

Globally, liver cancer has the third highest mortality rate among all types of cancer due to the invasive and metastatic capacities of liver tumor cells. MicroRNA (miR) is a class of non-coding RNAs that participate in the development of liver cancer. The aim of the present study was to explore the molecular mechanisms by which miR-221-3p and miR-15b-5p promote the proliferation and invasion of liver cancer cells through targeting axis formation inhibitor 2 (Axin2) and to identify suitable targets for the treatment of liver cancer. The expression levels of miR-221-3p and miR-15b-5p were determined in liver cancer tissues and cells by quantitative PCR, and the association between miR-221-3p, miR-15b-5p and Axin2 expression in liver cancer cells was analyzed using cell transfection. The results demonstrated that miR-221-3p and miR-15b-5p levels were upregulated in liver cancer tissues and cell lines, and results from predictive bioinformatic analysis and identification revealed that Axin2 was the common target gene of miR-221-3p and miR-15b-5p. miR-221-3p and miR-15b-5p may be used as prognostic indicators for liver cancer. The miR-221-3p/miR-15b-5p-Axin2 axis may serve as a therapeutic target in patients with liver cancer.