Department of Biochemistry and Molecular Biology, Southwest Medical University, Luzhou, Sichuan Province, PR China.
Medicine (Baltimore). 2021 Nov 19;100(46):e27598. doi: 10.1097/MD.0000000000027598.
The family of histone H2A proved that there are a lot of variants associated with cancer development. The link between HIST3H2A and pancreatic cancer has never been noted before. Our research suggests that HIST3H2A affects pancreatic tumor immune process and prognosis of patients, through the JAK STAT pathway, so it is expected to become the biomarker of pancreatic cancer.Gene expression profiles and clinical data of pancreatic cancer patients were downloaded from The Cancer Genome Atlas database (TCGA) and The Genotype Tissue Expression (GETx) project. R software (Rx64 3.6.0) was utilized to analyze. Gene set enrichment analysis (GSEA) was used to analyze HIST3H2A related signaling pathways in pancreatic cancer. CIBERSORT is applied to estimate the compositional patterns of the 22 types of immune cell fraction based on bulk expression data.HIST3H2A was expressed at higher in pancreatic cancer tissues than normal pancreatic tissues. Kaplan-Meier survival analysis suggested that the level of HIST3H2A expression affect prognosis of pancreatic cancer patients. Univariate Cox analysis and Multivariate Cox analysis suggested that HIST3H2A expression is a prognostic factor of pancreatic cancer. Cor expression analysis indicated that the genes positively correlated with HIST3H2A expression trend were DCST1-AS1, HIST1H2BD, SLC12A9-AS1. GSEA showed that the JAK-STAT signaling pathway was enriched in the HIST3H2A high expression phenotype, whereas intestinal network for IgA production, Asthma and Chemokine signaling pathway were enriched in the HIST3H2A low expression phenotype. In additional, results showed that CD8 T cells (P = .007), activated CD4 memory T cells (P = .001), and monocytes (P = .002) were more abundant in lower HIST3H2A expression groups.HIST3H2A is a promising biomarker for predicting prognosis of pancreatic cancer, and it could be a potential therapeutic target. HIST3H2A might regulate the progression of tumor immune in pancreatic cancer through modulating the JAK-STAT pathway. In addition, the role HIST3H2A in pancreatic cancer may be related to DCST1-AS1, HIST1H2B, SLC12A9-AS1. However, more research is necessary to validate findings.
组蛋白 H2A 家族被证实与癌症的发生发展密切相关，HIST3H2A 与胰腺癌的关联此前从未被报道过。我们的研究表明，HIST3H2A 通过 JAK-STAT 通路影响胰腺肿瘤免疫过程和患者预后，有望成为胰腺癌的生物标志物。从癌症基因组图谱数据库（TCGA）和基因型组织表达（GETx）项目中下载胰腺癌患者的基因表达谱和临床数据。使用 R 软件（Rx64 3.6.0）进行分析。基因集富集分析（GSEA）用于分析胰腺癌中 HIST3H2A 相关信号通路。CIBERSORT 应用于基于批量表达数据估计 22 种免疫细胞亚群的组成模式。HIST3H2A 在胰腺癌组织中的表达高于正常胰腺组织。Kaplan-Meier 生存分析表明，HIST3H2A 表达水平影响胰腺癌患者的预后。单因素 Cox 分析和多因素 Cox 分析表明，HIST3H2A 表达是胰腺癌的预后因素。相关表达分析表明，与 HIST3H2A 表达趋势呈正相关的基因是 DCST1-AS1、HIST1H2BD、SLC12A9-AS1。GSEA 显示 JAK-STAT 信号通路在 HIST3H2A 高表达表型中富集，而 IgA 产生的肠道网络、哮喘和趋化因子信号通路在 HIST3H2A 低表达表型中富集。此外，结果表明，HIST3H2A 低表达组中 CD8+T 细胞（P=0.007）、活化的 CD4 记忆 T 细胞（P=0.001）和单核细胞（P=0.002）更为丰富。HIST3H2A 是预测胰腺癌预后的有前途的生物标志物，可能是潜在的治疗靶点。HIST3H2A 可能通过调节 JAK-STAT 通路调节肿瘤免疫在胰腺癌中的进展。此外，HIST3H2A 在胰腺癌中的作用可能与 DCST1-AS1、HIST1H2BD、SLC12A9-AS1 有关。但是，还需要更多的研究来验证这些发现。
