Wei Fang-Ze, Mei Shi-Wen, Wang Zhi-Jie, Chen Jia-Nan, Zhao Fu-Qiang, Li Juan-, Xiao Ti-Xian, Zhao Wei, Ma Yun-Bin, Yuan Wei, Liu Qian
Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Oncol. 2022 Aug 5;12:884474. doi: 10.3389/fonc.2022.884474. eCollection 2022.
Colorectal cancer (CRC) is the most common digestive tumor in the world and has a high mortality rate. The development and treatment of CRC are related to the immune microenvironment, but immune response-related prognostic biomarkers are lacking. In this study, we used The Cancer Genome Atlas (TCGA) to explore the tumor microenvironment (TME) and weighted gene coexpression network analysis (WGCNA) to identify significant prognostic genes. We also identified differentially expressed genes in the TCGA data and explored immune-related genes and transcription factors (TFs). Then, we built a TF regulatory network and performed a comprehensive prognostic analysis of an lncRNA-associated competitive endogenous RNA network (ceRNA network) to build a prognostic model. CCR8 and HAMP were identified both in the WGCNA key module and as immune-related genes. HAMP had good prognostic value for CRC and was highly expressed in CRC tissues and had a negative correlation with CD4 T cells and M0 macrophages based on immunohistochemistry and immunofluorescence staining of clinical specimens.We found that HAMP had high prognostic and therapeutic target value for CRC and was associated with liver metastasis. These analysis results revealed that HAMP may be a candidate immune-related prognostic biomarker for CRC.
结直肠癌(CRC)是全球最常见的消化道肿瘤,死亡率很高。CRC的发生发展及治疗与免疫微环境相关,但缺乏免疫反应相关的预后生物标志物。在本研究中,我们利用癌症基因组图谱(TCGA)探索肿瘤微环境(TME),并通过加权基因共表达网络分析(WGCNA)来识别显著的预后基因。我们还在TCGA数据中鉴定了差异表达基因,并探索了免疫相关基因和转录因子(TFs)。然后,我们构建了一个TF调控网络,并对一个lncRNA相关的竞争性内源性RNA网络(ceRNA网络)进行了综合预后分析,以构建一个预后模型。CCR8和HAMP在WGCNA关键模块中均被鉴定为免疫相关基因。基于临床标本的免疫组织化学和免疫荧光染色,HAMP对CRC具有良好的预后价值,在CRC组织中高表达,且与CD4 T细胞和M0巨噬细胞呈负相关。我们发现HAMP对CRC具有较高的预后和治疗靶点价值,且与肝转移相关。这些分析结果表明,HAMP可能是CRC的一个候选免疫相关预后生物标志物。