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Updated: Aug 13, 2025
Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
Role of NCF2 as a potential prognostic factor and immune infiltration indicator in hepatocellular carcinoma
Ning Huang1, Jing Zhang1, Shuwen Kuang1
1Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background:
Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths globally. The tumor microenvironment (TME) plays a crucial role in the prognosis and treatment of HCC. Hence, it is important to exploit new biomarkers for survival surveillance and TME estimation of HCC.
Methods:
HCC samples data was collected from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database, and clinical samples were collected from our center. The TME of HCC were explored with ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data), ssGSEA (single sample Gene Sets Enrichment Analysis) and CIBERSORT algorithm. Differentially expressed genes were analyzed with functional enrichment analysis. Immunohistochemistry was implemented to validate the results.
Results:
Based on TCGA database, we found that Neutrophil Cytosolic Factor 2 (NCF2) was significantly associated with the prognosis of HCC patients, involved in immune-related biological processes of HCC and closely associated with some types of immunocompetent cells. The survival analysis based on NCF2 expression assessed by immunohistochemistry also confirmed that NCF2-positive group had a shorter relapse free survival (RFS) and overall survival (OS) than NCF2-negative group. Multivariate Cox regression revealed NCF2 expression level and lymphovascular space invasion (LVSI) were independent risk factors for HCC patients. Receiver operating characteristic curves showed that the combination of NCF2 and LVSI had higher predictive efficacy on the 1-year RFS rate and 5-year OS rate than each of them alone. Besides, the expression level of NCF2 was positively associated with M0 and M2 macrophages infiltration. Furthermore, NCF2 expression was positively correlated with CSF1, IL4, IL10, CD206, CD163, CSF1R and TGFβ1.
Conclusion:
We proposed that higher NCF2 expression predicted an adverse prognosis and more M2 macrophages infiltration in HCC patients.
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