Bioinformatics Analysis of LGR4 in Colon Adenocarcinoma as Potential Diagnostic Biomarker, Therapeutic Target and Promoting Immune Cell Infiltration

Abstract

Colon adenocarcinoma is one of the tumors with the highest mortality rate, and tumorigenesis or development of colon adenocarcinoma is the major reason leading to patient death. However, the molecular mechanism and biomarker to predict tumor progression are currently unclear. With the goal of understanding the molecular mechanism and tumor progression, we utilized the TCGA database to identify differentially expressed genes. After identifying the differentially expressed genes among colon adenocarcinoma tissues with different expression levels of LGR4 and normal tissue, protein–protein interaction, gene ontology, pathway enrichment, gene set enrichment analysis, and immune cell infiltration analysis were conducted. Here, the top 10 hub genes, i.e., ALB, F2, APOA2, CYP1A1, SPRR2B, APOA1, APOB, CYP3A4, SST, and GCG, were identified, and relative correlation analysis was conducted. Kaplan–Meier analysis revealed that higher expression of LGR4 correlates with overall survival of colon adenocarcinoma patients, although expression levels of LGR4 in normal tissues are higher than in tumor tissues. Further functional analysis demonstrated that higher expression of LGR4 in colon adenocarcinoma may be linked to up-regulate metabolism-related pathways, for example, the cholesterol biosynthesis pathway. These results were confirmed by gene set enrichment analysis. Immune cell infiltration analysis clearly showed that the infiltration percentage of T cells was significantly higher than other immune cells, and TIMER analysis revealed a positive correlation between T-cell infiltration and LGR4 expression. Finally, COAD cancer cells, Caco-2, were employed to be incubated with squalene and 25-hydroxycholesterol-3-sulfate, and relative experimental results confirmed that the cholesterol biosynthesis pathway involved in modulating the proliferation of COAD tumorigenesis. Our investigation revealed that LGR4 can be an emerging diagnostic and prognostic biomarker for colon adenocarcinoma by affecting metabolism-related pathways.

Feasibility and Clinical Utility of Reporting Hereditary Cancer Predisposition Pathogenic Variants Identified in Research Germline Sequencing: A Prospective Interventional Study

“…Previous research suggests the cholesterol biosynthesis pathway may be upregulated in colon cancer and could be involved in tumorigenesis. 57 Two unrelated patients with head/neck squamous cell carcinoma had SCN5A PGVs (proportion in head/neck cancer: 2.4%, 2/82), which codes for a voltage-gated sodium channel and confers risk for Brugada and Romano-Ward prolonged QT syndromes. Other voltage-gated sodium channels are upregulated in oral squamous cell carcinomas and may be involved in tumoral progression through the Wnt/beta-catenin signaling pathway.…”

A Novel Cuproptosis-Related Prognostic Model and the Hub Gene FDX1 Predict the Prognosis and Correlate with Immune Infiltration in Clear Cell Renal Cell Carcinoma

“…Loss of VHL function could induce the abnormal accumulation of HIF- α and activation of downstream target genes, promoting the development of ccRCC [ 7 , 8 ]. Nowadays, though the vast amount of data allows to enhance the reliability and accuracy of the prediction model, there were still no effective diagnostic model or markers in ccRCC [ 9 , 10 ]. Moreover, while the field of molecular therapy has seen great advances, including antivascular endothelial growth factor drugs and immune inhibitors, challenges still remain for further improving prognosis because of drug resistance and adverse reactions [ 11 , 12 ].…”