弥漫大B细胞淋巴瘤预后相关基因与患者预后 及肿瘤浸润性免疫细胞比例的相关性.

Objective　 To screen out the prognosis-related genes in diffuse large B-cell lymphoma (DLBCL) and to confirm the relationship between the expression of prognosis-related genes and patients' survival and the proportion of tu⁃ mour-infiltrating immune cells (TICs) to provide new targets for the treatment and prognosis of DLBCL. Methods　 GSE56315, GSE12453 and GSE87371 microarray data were obtained from GEO, and DLBCL prognosis-associated genes were screened using the R "limma" package. Prognosis-related genes were analyzed for survival, independent prognosis, and correlation between prognosis-related gene expression levels and clinical parameters. The target genes in the GSE87371 datasets were categorised into high and low expression groups according to their median expression values, and the 5-year OS rates and 95%CIs of the high and low expression groups were extracted from the "survival" package in R. The correlation between the target genes and prognosis was then analyzed using COX risk regression models. Finally, "for loop" was used to analyse the relationship between the target gene and clinical parameters such as age, gender and clinical stage of DLBCL patients. The functional pathways of DLBCL prognosis-related genes in DLBCL were analyzed by GSEA enrichment. Finally, the CIBERSORT algorithm was used to calculate the proportion of TICs in DLBCL tis⁃ sues and to analyse the relationship between the expression levels of prognosis-related genes and the proportion of TICs. Results　 The merged MERGE gene set of GSE12353 and GSE56315 was screened. We obtained 445 (301 up-regulated genes and 143 down-regulated genes) differentially expressed genes； 57 prognosis-related genes( 17 negatively and 40 pos⁃ itively correlated) were obtained from the GSE87371 dataset, and the 301 differentially up-regulated genes and the 17 neg⁃ atively correlated genes were intersected to obtain membrane linked protein 1 (ANXA1), which was a DLBCL prognosisassociated gene. Survival analysis suggested a 5-year OS rate of 3. 56% (95%CI 1. 17%-10. 7%) in the high ANXA1 ex⁃ pression group and 17. 49%( 95%CI 11. 8%-29. 9%) in the low ANXA1 expression group, suggesting a poor prognosis for DLBCL patients in the high ANXA1 expression group (P<0. 001). ANXA1 was an independent prognostic factor (P< 0. 05) and its expression level was not correlated with clinical parameters of patients (P>0. 05). GSEA functional enrich⁃ ment analysis showed that the ANXA1 high expression group was enriched in chemokine signalling pathway, MAPK signal⁃ ling pathway, ECM receptor interaction and JAK-STAT signalling pathway. Immuno-infiltration analysis showed that T cells (49%) and macrophages (31%) were more predominant in DLBCL tissues, and ANXA1 expression was positively correlated with macrophage M2, plasma cells, activated CD4+ memory T cells, CD8+T cells, and γδ T cells. Conclu⁃ sion　 ANXA1 is associated with the prognosis of DLBCL patients, and its high expression is related to the poor prognosis and the proportion of TICs； the enrichment signal pathway mainly includes tumor-related signaling pathways such as the chemokines signaling pathway. [ABSTRACT FROM AUTHOR]