Purpose Liver cancer is one of the most common malignant tumors in China, ranked 5th among the malignant common tumors in the world, which is still difficult to diagnose early and treat effectively. Therefore, exploring some indicators for prognostic prediction is imperative in the treatment of liver cancer. Methods Liver cancer data was obtained from The Cancer Genome Atlas (TCGA). We obtained differentially expressed genes (DEGs) by R software from TCGA database. Risk scores were acquired to assess the weighted gene-expression levels by Cox regression analysis and predict the prognosis of patients with liver cancer. Using the KEGG and GO databases, pathway enrichment was performed by identifying the analysis of DEGs. The display of receiver-operating characteristic (ROC) curves and area under the curve (AUC) could show the validity and the prognostic value of this model in liver cancer. Results In total, 1897 DEGs of transcriptome genes in liver cancer and 1197 DEGs of clinical data were extracted from the TCGA database. We identified a novel five-gene signature associated with liver cancer, including CDCA8, NR0B1, GAGE2A, AC018641.1, and SPANXC. Among of them, CDCA8 and NR0B1 were negatively related to 5-year OS, displaying a worse prognosis (P < 0.05). In particular, we also found that GAGE2A is related to lymphatic metastasis from the clinical data analysis in liver cancer. Receiver-operating characteristic (ROC) curve assessed the accuracy and sensitivity of the gene signature. In the heat map, each of the five genes for patients was presented with the distribution of the risk score. Conclusions We figured out a novel five-gene signature for the prognosis of patients with liver cancer, which may be an effective predictor for patients’ prognosis in the future.
This study aimed on exploration of the system-wide effects of the alcohol-induced increase in the content of cytochrome P450 2E1 (CYP2E1) in the human liver on drug metabolism. Using membrane incorporation of purified CYP2E1 modified with photoreactive crosslinkers benzophenone-4-maleimide (BPM) and 4-(N-succinimidylcarboxy)benzophenone (BPS), we explored the array of its protein-protein interactions (proteome) in human liver microsomes (HLM) with chemical cross-linking mass spectrometry (CXMS). Exposure of bait-incorporated HLM samples to light was followed by isolation of the His-tagged bait protein and its cross-linked aggregates on Ni-NTA agarose. Analyzing the individual bands of SDS-PAGE slabs of thereby isolated protein with the toolset of untargeted proteomics, we detected the cross-linked dimeric and trimeric complexes of CYP2E1 with other drug-metabolizing enzymes. Among the most extensively cross-linked partners of CYP2E1 are cytochromes P450 2A6, 3A4, 2C9, and 4A11. We also detected the conjugates of CYP2E1 with UDP-glucuronosyltransferases (UGTs) 1A6, 1A9, 2B4, 2B15, and 2B17. These results demonstrate the exploratory power of the proposed CXMS strategy and corroborate the concept of tight functional integration in the human drug-metabolizing ensemble through protein-protein interactions of the constituting enzymes. Of particular interest is the observation of efficient cross-linking of CYP2E1 with CYP4A11. This enzyme plays a central role in the synthesis of vasoactive eicosanoids and its interactions with alcohol-inducible CYP2E1 may shed light on the mechanisms of alcohol-induced hypertension.
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