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.

Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer.

BACKGROUND: Chemotherapy induced diarrhea (CID) is a common side effect in patients receiving chemotherapy for cancer. The aim of our study was to explore the association between gut microorganisms and CID from the CapeOX regimen in resected stage III colorectal cancer (CRC) patients. RESULTS: After screening and identification, 17 stool samples were collected from resected stage III CRC patients undergoing the CapeOX regimen. Bacterial 16S ribosomal RNA genes was sequenced, and a bioinformatics analysis was executed to screen for the distinctive gut microbiome and the functional metabolism associated with CID due to the CapeOX regimen. The gut microbial community richness and community diversity were lower in CID (p < 0.05 vs control group). Klebsiella pneumoniae was the most predominant species (31.22%) among the gut microbiome in CRC patients with CID. There were 75 microorganisms with statistically significant differences at the species level between the CRC patients with and without CID (LDA, linear discriminant analysis score > 2), and there were 23 pathways that the differential microorganisms might be involved in. CONCLUSIONS: The gut microbial community structure and diversity have changed in CRC patients with CID. It may provide novel insights into the prevention and treatment of CID.