Colorectal cancer and gut viruses: a visualized analysis based on CiteSpace knowledge graph.

Background: Gut microbiome is a complex community of microbes present in the human gut and plays an important role in the occurrence and progression of colorectal cancer (CRC). However, the relationship between virus and CRC has not been fully understood. Objective: To explore the hot spots and research trends in the field of CRC and virus. Methods: By using the bibliometric analysis tool CiteSpace and based on the articles of the Web of Science Core Collection (WoSCC) database, the country, institution, highly cited literature, keywords and so on were visually analyzed. Results: A total of 356 research articles on CRC from 2001 to 2023 were thoroughly analyzed. The USA and China have made the largest contribution in the field of virus and CRC. The Helmholtz Association published the most papers. There were relatively few cooperations among institutions from different countries. The results of keyword cluster analysis proved that the literature on the relationship between human cytomegalovirus (CMV) and CRC was the most widely studied aspect in this field. "Gut microbiota," "inflammatory bowel disease," "hepatitis b virus," and "human papillomavirus infection" are the current research hotspots; "oncolytic virus," "apoptosis," and "gut microbiome" are the recent research frontiers and should be paid closer attention. Conclusion: By using CiteSpace bibliometric software, the visual analysis reflected the research trends and hot topics of virus and CRC. In addition, the prevalence and mechanism of specific virus on CRC were also reviewed, which provides valuable references for future CRC research.

Immune-Related Biomarkers Associated with Lung Metastasis from the Colorectal Cancer Microenvironment.

Immune-associated biomarkers can predict lung metastases from colorectal cancer. Differentially expressed genes (DEGs) were screened from sample data extracted from gene expression omnibus (GEO) database. The DEGs were screened from the lung metastasis (LM) and primary cancer (PC) groups of the Moffitt Cancer Center cohort dataset. Then, the tumor immune microenvironment and abundance of immune cell infiltration analyses were performed, and the immune-related DEGs were retrieved. In addition, the transcription factor (TF)-miRNA-mRNA network was constructed and enrichment analyses of the immune-related DEGs and upregulated and downregulated DEGs were carried out. Then, the protein-protein interaction (PPI) network was conducted and the drug-gene interaction was predicted. A total of 268 DEGs were screened. The Immune_Score of samples in the LM group was significantly higher compared with the PC group. The infiltration ratio of M0 macrophages and M2 macrophages of samples was higher than others. A total of 54 immune-related DEGs in M0 macrophages were screened. Moreover, the TF-miRNA-mRNA network was constructed among 8 miRNA-mRNA and 50 TF-mRNA, and the secreted phosphoprotein 1 was regulated by 12 TFs, and the oxidized low-density lipoprotein receptor 1 was regulated by 3 miRNAs and 3 TFs. The TF SAM pointed domain containing ETS TF was also a downregulated DEG. The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the DEGs in the TF-miRNA-mRNA network were mainly involved in the interleukin-7 signaling pathway and cell adhesion molecules. In total, 23 protein interactions in this PPI network of M0 macrophage cells were involved in 27 mRNAs. There were 38 drug-gene interactions of immune-related DEGs of M0 macrophage cells predicted to contain 34 small molecule drugs and 8 mRNAs. Finally, the CON cohort dataset verified that the infiltration ratio of M0 and M2 macrophages of the samples was higher.

Prognostic model based on six PD-1 expression and immune infiltration-associated genes predicts survival in breast cancer.

BACKGROUND: The prognosis of breast cancer (BC) was associated with the expression of programmed cell death-1 (PD-1). METHODS: BC-related expression and clinical data were downloaded from TCGA database. PD-1 expression with overall survival and clinical factors were investigated. Gene set variation analysis (GSVA) and weighted gene correlation network analysis were performed to investigate the PD-1 expression-associated KEGG pathways and genes, respectively. Immune infiltration was analyzed using the ssGSEA algorithm and DAVID, respectively. Univariate and multivariable Cox and LASSO regression analyses were performed to select prognostic genes for modeling. RESULTS: High PD-1 expression was related to prolonged survival time (P = 0.014). PD-1 expression status showed correlations with age, race, and pathological subtype. ER- and PR-negative patients exhibited high PD-1 expression. The GSVA revealed that high PD-1 expression was associated with various immune-associated pathways, such as T cell/B cell receptor signaling pathway or natural killer cell-mediated cytotoxicity. The patients in the high-immune infiltration group exhibited significantly higher PD-1 expression levels. In summary, 397 genes associated with both immune infiltration and PD-1 expression were screened. Univariate analysis and LASSO regression model identified the six most valuable prognostic genes, namely IRC3, GBP2, IGJ, KLHDC7B, KLRB1, and RAC2. The prognostic model could predict survival for BC patients. CONCLUSION: High PD-1 expression was associated with high-immune infiltration in BC patients. Genes closely associated with PD-1, immune infiltration and survival prognosis were screened to predict prognosis.

Screening and analysis of RNAs associated with activated memory CD4 and CD8 T cells in liver cancer.

BACKGROUND: Liver cancer is one of the most common malignant tumors in the world. T cell-mediated antitumor immune response is the basis of liver cancer immunotherapy. OBJECTIVE: To screen and analyze the RNAs associated with activated memory CD4 T cells and CD8 T cells in liver cancer. METHODS: ESTIMATE was used to calculate the stromal and immune scores of tumor samples, which were downloaded from The Cancer Genome Atlas (TCGA). The differentially expressed genes (DEGs) in high and low stromal and immune scores were screened, followed by functional enrichment of overlapped DEGs. We then conducted a survival analysis to identify immune-related prognostic indicators and constructed protein-protein interaction (PPI) networks and ceRNA networks. Finally, chemical small-molecule-target interaction pairs associated with liver cancer were screened. RESULTS: A total of 55,955 stromal-related DEGs and 1811 immune-related DEGs were obtained. The 1238 overlapped DEGs were enriched in 1457 biological process terms and 74 KEGG pathways. In addition, a total of 120 activated memory CD4 T cell-related genes and 309 CD8 T cell-related genes were identified. The survival analysis revealed that upregulated expression of T cell-related genes including EOMES, CST7, and CD5L indicated the favorable prognosis of liver cancer. EOMES was regulated by has-miR-23b-3p and has-miR-23b-3p was regulated by lncRNA AC104820.2 in the ceRNA network of activated memory CD4 T cell-related genes. In addition, EOMES was regulated by has-miR-23a-3p and has-miR-23a-3p was regulated by lncRNA AC000476.1 in the ceRNA network of CD8 T cells. CONCLUSION: T cell-related RNAs EOMES, CST7, CD5L, has-miR-23b-3p, and has-miR-23a-3p may be associated with the prognosis of liver cancer. And the molecular characteristics of these T cell-related genes were plotted.

Molecular characteristics associated with ferroptosis in hepatocellular carcinoma progression.

The aim of this study was to investigate the genes associated with ferroptosis and the progression of hepatocellular carcinoma (HCC). The RNA sequencing data of erastin-induced ferroptosis in HCC cells were downloaded from the Sequence Read Archive database with accession number SRP119173. The microarray dataset GSE89377 of HCC progression was downloaded from the Gene Expression Omnibus database. The ferroptosis-related genes were screened by differential analysis and HCC progression-related genes were screened by cluster analysis using Mfuzz. Then, the genes associated with ferroptosis and HCC progression were screened by Venn analysis, followed by functional enrichment, protein-protein interaction (PPI) analysis, and transcription factor (TF) prediction. Finally, survival analysis was performed using data from the Cancer Genome Atlas database. A total of 33 upregulated and 52 downregulated genes associated with HCC progression and ferroptosis were obtained, and these genes were significantly involved in the negative regulation of ERK1 and ERK2 cascades; the NAD biosynthetic process; alanine, aspartate, and glutamate metabolism; and other pathways. The PPI network contained 52 genes and 78 interactions, of which, cell division cycle 20 (CDC20) and heat shock protein family B (small) member 1 (HSPB1) were hub genes found in higher degrees. Among the 85 genes associated with HCC progression and ferroptosis, two TFs (activating TF 3 (ATF3) and HLF) were predicted, with HSPB1 targeted by ATF3. In addition, 26 genes that were found to be significantly correlated with the overall survival of HCC patients were screened, including CDC20 and thyroid hormone receptor interactor 13. Several genes associated with HCC progression and ferroptosis were screened based on a comprehensive bioinformatics analysis. These genes played roles in HCC progression and ferroptosis via the negative regulation of the ERK1 and ERK2 cascades; the NAD biosynthetic process; and alanine, aspartate, and glutamate metabolism. ATF3 and HSPB1 played important roles in HCC progression and ferroptosis, with HSPB1 possibly regulated by ATF3.

Effects of postoperative adjuvant chemotherapy and palliative chemotherapy on the gut microbiome in colorectal cancer.

BACKGROUND: The gut microbiome changes are related to the colorectal cancer (CRC). Chemotherapy is one of the main treatment methods for CRC. PURPOSE: To explore the effect of chemotherapy on the gut bacteria and fungi in CRC. METHODS: Total of 11 advanced CRC patients treated with the FOLFIRI regimen, 15 postoperative CRC patients treated with the XELOX regimen, and corresponding CRC patients without surgery and chemotherapy were recruited. The 16S ribosomal RNA and ITS sequences were sequenced, and bioinformatics analysis was executed to screen for the distinctive gut microbiome. RESULTS: The abundances of Veillonella, Humicola, Tremellomycetes and Malassezia were increased in postoperative CRC patients treated with the XELOX regimen. The abundances of Faecalibacterium, Clostridiales, phascolarctobacterium, Humicola and Rhodotorula were decreased, and the abundances of Candida, Magnusiomyces, Tremellomycetes, Dipodascaceae, Saccharomycetales, Malassezia and Lentinula were increased in advanced CRC patients treated with the FOLFIRI regimen. The abundances of Humicola, Rhodotorula, and Magnusiomyces were decreased, and the abundances of Candida, Tremellomycetes, Dipodascaceae, Saccharomycetales, Malassezia and Lentinula were increased in advanced CRC patients treated with the FOLFIRI regimen combined with cetuximab compared with those treated with the FOLFIRI regimen alone. CONCLUSIONS: The community structure of gut bacteria and fungi changes in chemotherapy on CRCs.

Analysis of prognosis, genome, microbiome, and microbial metabolome in different sites of colorectal cancer.

BACKGROUND: The colorectum includes ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. Different sites of colorectal cancer (CRC) are different in many aspects, including clinical symptoms, biological behaviour, and prognosis. PURPOSE: This study aimed to analyse prognosis, genes, bacteria, fungi, and microbial metabolome in different sites of CRC. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database and STAT were used to statistically describe and analyse the prognosis in different sites of CRC. RNA sequences of CRC from Broad Institute's GDAC Firehose were re-annotated and reanalysed based on different sites using weighted gene co-expression network analysis (WGCNA). The Kaplan-Meier method was used to analyse the prognosis and Cytoscape was used to construct a drug-target network based on DGIdb databases. Bacterial 16S V3-V4 and fungal ITS V3-V4 ribosomal RNA genes of stool samples were sequenced. Gas chromatography/mass spectrometry (GS/MS) was performed to detect the microbial metabolites in stool samples. Bioinformatics analysis was performed to compare distinct gut microorganisms and microbial metabolites between rectal and sigmoid cancers. RESULTS: The prognosis in CRC with different sites is significantly different. The closer to the anus predicted longer survival time. The difference between genes and co-expression pairs in CRC with different sites were constructed. The relative abundance of 112 mRNAs and 26 lncRNAs correlated with the sites of CRC were listed. Nine differentially expressed genes at different sites of CRC were correlated with prognosis. A drug-gene interaction network contained 227 drug-gene pairs were built. The relative abundance of gut bacteria and gut fungus, and the content of microbe-related metabolites were statistically different between rectal and sigmoid cancers. CONCLUSIONS: There are many differences in prognosis, genome, drug targets, gut microbiome, and microbial metabolome in different colorectal cancer sites. These findings may improve our understanding of the role of the CRC sites in personalized and precision medicine.

Relationship between intestinal microorganisms and T lymphocytes in colorectal cancer.

Colorectal cancer (CRC) is a common type of malignant cancer worldwide. Recent studies have identified the gut microbiota as the origin of CRC, and T lymphocyte-mediated immune functions have been shown to play an important role in this disease. By summarizing previous literature, we found that Fusobacterium nucleatum may protect CRC from immune cell attack by inhibiting T cells and influencing the production of many chemokines and cytokines. Some bacterial metabolites and probiotics have been shown to participate in the regulation of CRC through T cell-mediated molecular pathways. To visualize the relevant data, an association network of intestinal microorganisms and T lymphocytes associated with CRC was constructed. This work may provide direction for - and insight into - further research on the relationship between intestinal microorganisms and T lymphocytes in CRC.

Can Mitochondria DNA Provide a Novel Biomarker for Evaluating the Risk and Prognosis of Colorectal Cancer?

Colorectal cancer (CRC) was one of the most frequent cancers worldwide. Accurate risk and prognosis evaluation could obtain better quality of life and longer survival time for the patients. Current research hotspot was focus on the gene biomarker to evaluate the risk and prognosis. Mitochondrion contains its own DNA and regulates self-replicating so that it can be as a candidate biomarker for evaluating the risk and prognosis of colorectal cancer. But there were already huge controversies on this issue. The review was to summarize current viewpoints of the controversial issues and described our understanding from the four aspects including mtDNA copy number, mitochondrial displacement loop, mtDNA variation, and mtDNA microsatellite instability, wishing the summary of the mtDNA in colorectal cancer could provide a meaningful reference or a valuable direction in the future studies.