Characterization of a predictive signature for tumor microenvironment and immunotherapy response in hepatocellular carcinoma involving neutrophil extracellular traps
Ziwei Yuan,
Xuejia Yang,
Zujian Hu,
Yuanyuan Gao,
Penghua Yan,
Fan Zheng,
Yangyang Guo,
Xiaowu Wang,
Jingzong Zhou
Affiliations
Ziwei Yuan
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China; Department of Endocrinology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China
Xuejia Yang
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
Zujian Hu
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
Yuanyuan Gao
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
Penghua Yan
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
Fan Zheng
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
Yangyang Guo
Department of General Surgery, Ningbo First Hospital, Ningbo, 315000, China; Corresponding author.
Xiaowu Wang
Department of Burns and Skin Repair Surgery, The Third Affiliated Hospital of Whenzhou Medical University, Ruian, 325200, Zhejiang Province, China; Corresponding author.
Jingzong Zhou
Department of Endocrinology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China; Corresponding author.
Neutrophil extracellular traps (NETs) and other factors play a significant role in impacting the prognosis of patients with Hepatocellular carcinoma (HCC). Nevertheless, further research is warranted to fully elucidate the prognostic implications of NETs in patients with HCC. We employed a hierarchical clustering technique to examine the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) data and identified subtypes associated with NETs. Subsequently, we utilized LASSO regression analysis to identify a distinct gene expression pattern within these subtypes. The strength of this signature was further validated through analysis of TCGA-LIHC and International Cancer Genome Consortium-Liver Cancer (ICGC-LIRI-JP) data. Our findings resulted in the construction of a six-gene signature related to NETs, which can predict survival outcomes in HCC patients. To enhance the predictive accuracy of our tool, we developed a nomogram that integrates the NETs signature with clinicopathological characteristics. We validated the significance of NETs in HCC patients using qRT-PCR and immunohistochemistry assays, along with in vitro experiments targeting high-risk genes. Furthermore, our exploration of the immune microenvironment uncovered augmented immune-specific metrics within the low-risk cohort, implying potential disparities in immune-related attributes between the high-risk and low-risk contingents. In summary, the NETs signature we discovered serves as a valuable biomarker and provides guidance for personalized therapy in HCC patients.
