期刊
FRONTIERS IN GENETICS
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2022.989779
关键词
hepatocellular carcinoma; WGCNA; neutrophils; risk score; tumor immune microenvironment
资金
- Henan Province Medical Science and Technology Research Program Joint Construction Project [LHGJ20200473]
- Clinical study of neoadjuvant chemotherapy combined with nanometer ablation in the treatment of locally advanced pancreatic cancer
- Beijing Kangmeng Charity Foundation [KYBX2022000163]
This study comprehensively analyzed the prognostic features related to neutrophils, which will help in prognostic prediction and advance individualized treatment.
Background: Growing evidence suggests that infiltrating neutrophils are key players in hepatocellular carcinoma (HCC) tumor progression. However, a comprehensive analysis of the biological roles of neutrophil infiltration and related genes in clinical outcomes and immunotherapy is lacking.Methods: HCC samples were obtained from the TCGA and GEO databases. The CIBERSORT algorithm was used to reveal the TIME landscape. Gene modules significantly associated with neutrophils were found using weighted gene co-expression network analysis (WGCNA), a dynamic tree-cut algorithm, and Pearson correlation analysis. Genes were screened using Cox regression analysis and LASSO and prognostic value validation was performed using Kaplan-Meier curves and receiver operating characteristic (ROC) curves. Risk scores (RS) were calculated and nomograms were constructed incorporating clinical variables. Gene set variation analysis (GSVA) was used to calculate signaling pathway activity. Immunophenoscore (IPS) was used to analyze differences in immunotherapy among samples with different risk scores. Finally, the relationship between RS and drug sensitivity was explored using the pRRophetic algorithm.Results: 10530 genes in 424 samples (50 normal samples, 374 tumor samples) were obtained from the TCGA database. Using WGCNA, the MEbrown gene module was most associated with neutrophils. Nine genes with prognostic value in HCC (PDLIM3, KLF2, ROR2, PGF, EFNB1, PDZD4, PLN, PCDH17, DOK5) were finally screened. Prognostic nomograms based on RS, gender, tumor grade, clinical stage, T, N, and M stages were constructed. The nomogram performed well after calibration curve validation. There is an intrinsic link between risk score and TMB and TIME. Samples with different risk scores differed in different signaling pathway activity, immunopharmaceutical treatment and chemotherapy sensitivity.Conclusion: In conclusion, a comprehensive analysis of neutrophil-related prognostic features will help in prognostic prediction and advance individualized treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据