Role of NCF2 as a potential prognostic factor and immune infiltration indicator in hepatocellular carcinoma.
Role of NCF2 as a potential prognostic factor and immune infiltration indicator in hepatocellular carcinoma.
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肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一。肿瘤微环境（TME）在HCC的预后和治疗中起着至关重要的作用。因此，开发新的生物标志物用于HCC的生存监测和TME估计是重要的。HCC样本数据收集自癌症基因组图谱（TCGA）和国际癌症基因组联盟（ICGC）数据库，临床样本收集自本中心。用ESTIMATE（Estimation of Stromal and Immune Cells in Malignant Tumor tissues using Expression data）、ssGSEA（single sample Gene Sets Enrichment Analysis）和CIBERSORT算法对HCC的TME进行了研究。用功能富集分析法对差异表达基因进行分析。免疫组织化学方法验证结果。基于TCGA数据库，我们发现神经细胞溶质因子2（NCF 2）与HCC患者的预后显著相关，参与HCC的免疫相关生物学过程，并与某些类型的免疫活性细胞密切相关。基于免疫组化评估的NCF 2表达的生存分析也证实，NCF 2阳性组的无复发生存期（RFS）和总生存期（OS）短于NCF 2阴性组。多因素考克斯回归分析显示NCF 2表达水平和淋巴血管间隙侵犯（LVSI）是HCC患者的独立危险因素。受试者工作特征曲线显示，NCF 2和LVSI联合使用对1年RFS率和5年OS率的预测有效性高于单独使用。此外，NCF 2的表达水平与M0和M2巨噬细胞浸润呈正相关。NCF 2表达与CSF 1、IL 4、IL 10、CD 206、CD 163、CSF 1 R、TGFβ1呈正相关。我们认为，NCF 2的高表达预示着肝癌患者的不良预后和更多的M2巨噬细胞浸润。在TCGA-LIHC数据集中筛选出的预后和免疫相关基因用于建立预后模型。其中一个中枢基因NCF 2被认为是HCC患者的独立预后因子，也是通过调节巨噬细胞极化来调节HCC肿瘤微环境（TME）的潜在因子。
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. 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. 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. We proposed that higher NCF2 expression predicted an adverse prognosis and more M2 macrophages infiltration in HCC patients. Prognostic and immune related genes screened out in TCGA‐LIHC dataset were used for establishing a prognostic model. And a hub gene, NCF2, was identified as an independent prognostic factor of HCC patients as well as a potential factor to modulate the tumor microenvironment (TME) in HCC via regulating the polarization of macrophages.
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影响因子：
29.4
作者：
Roayaie S;Blume IN;Thung SN;Guido M;Fiel MI;Hiotis S;Labow DM;Llovet JM;Schwartz ME
通讯作者：
Schwartz ME
影响因子：
24.5
作者：
Chew V;Chen J;Lee D;Loh E;Lee J;Lim KH;Weber A;Slankamenac K;Poon RT;Yang H;Ooi LL;Toh HC;Heikenwalder M;Ng IO;Nardin A;Abastado JP
通讯作者：
Abastado JP
影响因子：
13.5
作者：
Kumada, T;Nakano, S;Sassa, T
通讯作者：
Sassa, T
影响因子：
3.1
作者：
Martinez, Fernando Oneissi;Sica, Antonio;Locati, Massimo
通讯作者：
Locati, Massimo
与 M2 巨噬细胞和 T 细胞功能障碍相关的胶质母细胞瘤新型巨噬细胞相关基因预后指数。
影响因子：
7.3
作者：
通讯作者：
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