Identification of hub genes and pathways in lung metastatic colorectal cancer

Abstract

Background Colorectal cancer (CRC) is one of the most prevalent types of malignant tumours. Metastasis is the leading cause of cancer-related mortality, with lung metastases accounting for 32.9% of all metastatic CRCs. However, since the biological mechanism of lung metastatic CRC is poorly understood, limited therapeutic targets are available. In the present study, we aimed to identify the key genes and molecular processes involved in CRC lung metastasis. Methods The differentially expressed genes (DEGs) between primary and lung metastatic CRC patients were obtained from the Gene Expression Omnibus (GEO) database via the GEO2R tool. The enriched biological processes and pathways modulated by the DEGs were determined with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome Gene Sets analyses. The search tool Retrieval of Interacting Genes (STRING) and Cytoscape were used to construct a protein–protein interaction (PPI) network among DEGs. Results The DEGs were enriched in surfactant metabolism, cell–cell communication and chemokine signaling pathways. The defined hub genes were included CLU, SFTPD, CCL18, SPP1, APOE, BGN and MMP3. Among them, CLU, SFTPD and CCL18 might be associated with the specific lung tropism metastasis in CRC. In addition, the expression and prognostic values of the hub genes in CRC patients were verified in database of The Cancer Genome Atlas (TCGA) and GEO. Moreover, the protein levels of the hub genes were detected in primary and lung metastatic CRC cells, serum or tissues. Furthermore, SFTPD was confirmed to facilitate cellular proliferation and lung metastasis in CRC. Conclusion This bioinformatics study may provide a better understanding of the candidate therapeutic targets and molecular mechanisms for CRC lung metastasis.

Identification and prognostic analysis of candidate biomarkers for lung metastasis in colorectal cancer

“…In addition, PGE2 induces the increased expression of APOE mRNA in activated macrophages through the ERK1/2 signaling pathway, affecting cytokine secretion in macrophages, causing changes in cytokine microenvironment and destroying the balance between M1/M2 types of macrophages, thus affecting the occurrence and development of tumors. [ 35 ] Dai et al [ 36 ] reported that APOE was increased in CRC liver metastases and CRC lung metastases, which was positively associated with advanced stages and poor overall survival in CRC. Recent studies have demonstrated that APOE also contributes to DNA synthesis, cell proliferation, angiogenesis, and metastasis to facilitate tumorigenesis and progression.…”

Profilin 2 isoform expression is associated with lung metastasis of colorectal cancer according to a comprehensive gene expression study using a mouse model

“…The molecular mechanisms underlying lung metastasis in CRC have been extensively studied (8,9,12,13,(20)(21)(22)(23). However, the number of patients included in these studies was insufficient to obtain conclusive results owing to the heterogeneity of metastatic tumors (8,12,21).…”

Bioinformatics analyses and experimental validation of the role of phagocytosis in low‐grade glioma

“…STAP1 is utilized to construct a risk model in lung adenocarcinoma 58 and its methylation level is found to be linked to the process of liver cancer 59 . SFTPD is demonstrated to be a marker to assess the efficacy of EGFR‐TKIs in lung cancer 60 and facilitate lung metastasis in colorectal cancer 61 . AZU1 is reported to be upregulated in pancreatic ductal adenocarcinoma 62 and gastric cancer 63 .…”