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.

Circular RNA hsa_circ_0007507 May Serve as a Biomarker for the Diagnosis and Prognosis of Gastric Cancer.

PURPOSE: The morbidity and mortality of gastric cancer (GC) remain high worldwide. In recent years, circular RNAs (circRNAs) have attracted widespread attention among cancer researchers due to the stable ring structure. The present work aims to find serum circRNA biomarkers that can be used in clinical applications and effective diagnosis. METHODS: Hsa_circ_0007507 was extracted through circRNA sequencing. Exonuclease digestion assay, actinomycin D, agarose gel electrophoresis (AGE), and Sanger sequencing verified the potential of hsa_circ_0007507 as a biomarker. Besides, a real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was established to detect the level of expression of hsa_circ_0007507. Twenty cases of GC and the paired adjacent tissues were collected to verify its overexpression. Then, serum samples from 30 cases of colorectal cancer, 30 cases of thyroid cancer, and 30 cases of breast cancer were collected to verify their organ specificity. Additionally, serum samples from 80 healthy people, 62 gastritis patients, 31 intestinal metaplasia patients, and 100 GC patients were collected, and the diagnostic efficacy was evaluated through analysis of the receiver operating characteristic (ROC) curve. Furthermore, 16 post-operative GC samples, samples of 65 relapsed patients and 36 non-relapsed patients were collected to evaluate the prognosis of GC. RESULTS: The level of expression of hsa_circ_0007507 in GC tissues was up-regulated (p = 0.0121), which was consistent with the results of circRNA sequencing. Exonuclease digestion assay and actinomycin D confirmed that hsa_circ_0007507 had a stable structure and a longer half-life. In the analysis of organ specificity experiments, serum hsa_circ_0007507 did not have specificity for patients with colorectal cancer (p = 0.5319), thyroid cancer (p = 0.5422), or breast cancer (p = 0.5178). Analysis of diagnostic efficacy indicated that the expression of hsa_circ_0007507 was significantly higher than that of normal people (p <0.0001); the area under the ROC (AUC) was 0.832 (95% CI: 0.771-0.892); the diagnostic power of hsa_circ_0007507 was higher than that of CEA (AUC = 0.765, 95% CI: 0.697-0.833) and CA199 (AUC = 0.587, 95% CI: 0.504-0.67). Through diagnosis using a combination of the three, GC patients could be distinguished from normal people (AUC = 0.849), and higher diagnostic efficiency could be achieved. The expression of serum hsa_circ_0007507 in GC patients significantly decreased after surgery (p = 0.001). Besides, the expression of serum hsa_circ_0007507 in patients with post-operative recurrence was significantly up-regulated again (p = 0.0139). CONCLUSIONS: Serum hsa_circ_0007507 is differentially expressed in GC patients, post-operative GC patients, gastritis patients, intestinal metaplasia patients and relapsed patients, suggesting that serum hsa_circ_0007507 can be used as a new diagnostic and dynamic monitoring biomarker for GC.