Construction of a co-expression network and prediction of metastasis markers in colorectal cancer patients with liver metastasis.
Construction of a co-expression network and prediction of metastasis markers in colorectal cancer patients with liver metastasis.
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DOI：
10.21037/jgo-22-965
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发表时间：
2022-10
影响因子：
2.1
通讯作者：
Wu, Zhou
中科院分区：
文献类型：
--
作者：
Lin, Lihong;Zeng, Xiuxiu;Liang, Shanyan;Wang, Yunzhi;Dai, Xiaoyu;Sun, Yuechao;Wu, Zhou
关键词：
结直肠癌(CRC)是一种常见的全球性恶性肿瘤，具有高侵袭性、高转移性和预后不良等特点。结直肠癌通常转移到肝脏，转移的治疗是目前结直肠癌治疗中的一个重要课题。从国家生物技术信息中心(NCBI)基因表达总表(GEO)数据库下载人结直肠癌肝转移(CRCLM)基因芯片数据，以确定潜在的关键基因。对原发结直肠癌组织和转移性肝组织的差异表达基因(DEG)和DEmiRNAs进行鉴定。微环境细胞群体(MCP)计数器用于估计肿瘤微环境(TME)中免疫细胞的丰度，加权基因相关网络分析(WGCNA)用于构建共表达网络分析。进行基因本体论和京都基因与基因组百科全书(KEGG)途径浓缩分析，构建DES的蛋白质-蛋白质相互作用(PPI)网络，筛选基因模块。筛选了35对匹配的结直肠癌和肝转移基因表达谱，共鉴定出610个DEmiRNAs(265个上调，345个下调)和284个DEmiRNAs。DEGS主要集中在补体和凝血级联途径以及肾素分泌。免疫浸润性细胞包括中性粒细胞、单核细胞系和肿瘤相关成纤维细胞(CAF)在原发肿瘤组织和转移性肝组织中有显著差异。WGCN分析得到12个模块，鉴定出62个有显著互作的基因，这些基因主要与补体和凝血级联以及粘着斑通路有关。分别对F10、FGG、KNG1、MBL2、Proc、SERPINA1、CAV1、SPP1等8个基因进行了最佳子集回归分析和逐步回归分析。进一步分析发现，FGG、KNG1、CAV1和SPP1等4个基因与CRCLM显著相关。我们的研究提示补体和凝血级联以及局部黏附通路在CRCLM的发生发展中起重要作用，FGG、KNG1、CAV1和SPP1可能是CRCLM早期诊断的转移标志物。
Colorectal cancer (CRC) is a common global malignancy associated with high invasiveness, high metastasis, and poor prognosis. CRC commonly metastasizes to the liver, where the treatment of metastasis is both difficult and an important topic in current CRC management. Microarrays data of human CRC with liver metastasis (CRCLM) were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database to identify potential key genes. Differentially expressed (DE) genes (DEGs) and DEmiRNAs of primary CRC tumor tissues and metastatic liver tissues were identified. Microenvironment Cell Populations (MCP)-counter was used to estimate the abundance of immune cells in the tumor micro-environment (TME), and weighted gene correlation network analysis (WGCNA) was used to construct the co-expression network analysis. Gene Ontology and Kyoto Encyclopaedia of Gene and Genome (KEGG) pathway enrichment analyses were conducted, and the protein-protein interaction (PPI) network for the DEGs were constructed and gene modules were screened. Thirty-five pairs of matched colorectal primary cancer and liver metastatic gene expression profiles were screened, and 610 DEGs (265 up-regulated and 345 down-regulated) and 284 DEmiRNAs were identified. The DEGs were mainly enriched in the complement and coagulation cascade pathways and renin secretion. Immune infiltrating cells including neutrophils, monocytic lineage, and cancer-associated fibroblasts (CAFs) differed significantly between primary tumor tissues and metastatic liver tissues. WGCN analysis obtained 12 modules and identified 62 genes with significant interactions which were mainly related to complement and coagulation cascade and the focal adhesion pathway. The best subset regression analysis and backward stepwise regression analysis were performed, and eight genes were determined, including F10, FGG, KNG1, MBL2, PROC, SERPINA1, CAV1, and SPP1. Further analysis showed four genes, including FGG, KNG1, CAV1, and SPP1 were significantly associated with CRCLM. Our study implies complement and coagulation cascade and the focal adhesion pathway play a significant role in the development and progression of CRCLM, and FGG, KNG1, CAV1, and SPP1 may be metastatic markers for its early diagnosis.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
肿瘤纯度作为宫颈癌的预后和免疫治疗相关特征
DOI：
10.18632/aging.203714
发表时间：
2021-11-29
期刊：
Aging
影响因子：
--
作者：
Deng Y;Song Z;Huang L;Guo Z;Tong B;Sun M;Zhao J;Zhang H;Zhang Z;Li G
通讯作者：
Li G
影响因子：
4
作者：
Chen M;Chen S;Yang D;Zhou J;Liu B;Chen Y;Ye W;Zhang H;Ji L;Zheng Y
通讯作者：
Zheng Y
影响因子：
3.8
作者：
Engstrand J;Nilsson H;Strömberg C;Jonas E;Freedman J
通讯作者：
Freedman J
影响因子：
3.7
作者：
Katz SC;Bamboat ZM;Maker AV;Shia J;Pillarisetty VG;Yopp AC;Hedvat CV;Gonen M;Jarnagin WR;Fong Y;D'Angelica MI;DeMatteo RP
通讯作者：
DeMatteo RP