Use of machine learning-based integration to develop an immune-related signature for improving prognosis in patients with gastric cancer.

Gastric cancer is one of the most common malignancies. Although some patients benefit from immunotherapy, the majority of patients have unsatisfactory immunotherapy outcomes, and the clinical significance of immune-related genes in gastric cancer remains unknown. We used the single-sample gene set enrichment analysis (ssGSEA) method to evaluate the immune cell content of gastric cancer patients from TCGA and clustered patients based on immune cell scores. The Weighted Correlation Network Analysis (WGCNA) algorithm was used to identify immune subtype-related genes. The patients in TCGA were randomly divided into test 1 and test 2 in a 1:1 ratio, and a machine learning integration process was used to determine the best prognostic signatures in the total cohort. The signatures were then validated in the test 1 and the test 2 cohort. Based on a literature search, we selected 93 previously published prognostic signatures for gastric cancer and compared them with our prognostic signatures. At the single-cell level, the algorithms "Seurat," "SCEVAN", "scissor", and "Cellchat" were used to demonstrate the cell communication disturbance of high-risk cells. WGCNA and univariate Cox regression analysis identified 52 prognosis-related genes, which were subjected to 98 machine-learning integration processes. A prognostic signature consisting of 24 genes was identified using the StepCox[backward] and Enet[alpha = 0.7] machine learning algorithms. This signature demonstrated the best prognostic performance in the overall, test1 and test2 cohort, and outperformed 93 previously published prognostic signatures. Interaction perturbations in cellular communication of high-risk T cells were identified at the single-cell level, which may promote disease progression in patients with gastric cancer. We developed an immune-related prognostic signature with reliable validity and high accuracy for clinical use for predicting the prognosis of patients with gastric cancer.

CircRNA circ_0005273 contributes to the cisplatin resistance of cervical cancer cells by sponging miR-133b.

Circular RNAs (circRNAs) have been found to play important roles in drug resistance of human neoplasms. The aim of this study was to explore the effect of circ_0005273 on cisplatin (DDP) resistance of cervical cancer (CC) cells and identify its underlying mechanism. The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to analyse circ_0005273 and miR-133b expressions, and cell counting kit-8 (CCK-8), Hoechst 33258 staining and caspase-3 activity analysis were performed to evaluate cell proliferation and apoptosis. Luciferase reporter, RNA binding protein immunoprecipitation (RIP) and RNA pull down assays were applied to explore the interaction between circ_0005273 and miR-133b. Our research showed that circ_0005273 and miR-133b expressions were upregulated and downregulated in DDP-resistant CC cancer tissues and cell lines, respectively. Both of circ_0005273 and miR-133b levels were correlated with FIGO stage, DDP status and overall survival rates. Knockdown of circ_0005273 enhanced the sensitivity of DDP-resistant CC cells to DDP by inhibiting cell proliferation and promoting cell apoptosis. Furthermore, circ_0005273 acts as a competing endogenous RNA to modulate miR-133b expression. Downregulation of miR-133b partly reversed the DDP sensitivity of circ_0005273 knockdown in DDP-resistant CC cells. In summary, our study elucidated the role of circ_0005273/miR-133b axis in DDP resistance of CC cells, which might be a potential therapeutic target for DDP-resistant CC patients. Impact StatementWhat is already known on this subject? The detailed regulatory mechanisms underlying DDP chemoresistance are still unclear. Recently, literatures reported that circ_0005273 exerts a regulatory role in the tumorigenesis and progression of human cancers including thyroid carcinoma, pancreatic carcinoma, colorectal carcinoma and breast carcinoma.What do the results of this study add? Circ_0005273 contributes to the DDP resistance of CC cells via sponging miR-133b.What are the implications of these findings for clinical practice and/or further research? The results help to reverse DDP chemoresistance, and the circ_0005273/miR-133b axis might be a potential therapeutic target for DDP-resistant CC patients.

[Effect of bushen huayu composite on secretion of lymphocytic interleukin-2 and interleukin-2 receptor expression in the aged].

OBJECTIVE: To study the effect of Bushen Huayu Composite (BSHY) on interleukin-2 (IL-2) secretion and IL-2 receptor expression in the aged. METHODS: IL-2 was examined by methyl thiazolyl tetrazolium (MTT) method and IL-2 dependent cellular stains, IL-2 receptor expression was examined by FACS-indirect immunofluorescence. RESULTS: Aging could result in the decrease in lymphocytic IL-2 secretion and IL-2 receptor expression (P < 0.01, P < 0.05), which could be improved by BSHY (P < 0.01, P < 0.05). CONCLUSION: BSHY has significant up-regulatory effect on immune function of lymphocytes in the aged.