[The Predictive Value of Perioperative Inflammatory Indicatorsin Prognosis of the Intrahepatic Cholangiocarcinoma Patients after Hepatectomy].

OBJECTIVE: To evaluate the effect of perioperative inflammatory indicators on the prognosis of the patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy. METHODS: The clinical data of 231 ICC patients in the West China Hospital of Sichuan University from December 2006 to December 2016 were retrospectively collected. Neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR) and platelet-to-lymphocyte ratio (PLR) of patients during the perioperative period (pre-operation, postoperative day 3 and day 5) were analyzed. The X-tile software was used to determine the optimal cut-off values of NLR, d-NLR and PLR in pre-operation, postoperative day 3 and day 5. Based on the cut-off values, all patients were divided into high level group and low level group, and Kaplan-Meier methods were used to analyze the correlations of NLR, d-NLR and PLR with the disease-free survival (DFS) and overall survival (OS) of patients. Univariate and multivariate Cox regression models were applied to assess the prognostic values of NLR, d-NLR and PLR. Nomogram was established to predict the prognosis for ICC patients, and the predicting accuracy was evaluated by the Consistency index ( C-index). RESULTS: A total of 231 ICC patients including 115 males and 116 females were enrolled into this study, and the proportion of patients aged <60 years was 57.1%. Among the patients enrolled, 161 patients (69.7%) recurred and 156 patients (67.5%) died after hepatectomy. The median time of DFS and OS were 8.9 and 12.5 months respectively. The Kaplan-Meier curves showed that d-NLR and NLR levels in pre-operation, postoperative day 3 and day 5, together with the preoperative PLR level were correlated with the time of DFS ( P<0.05). Meanwhile, d-NLR and PLR levels in pre-operation, postoperative day 3 and day 5, together with the NLR level in pre-operation and postoperative day 3 were correlated with the time of OS ( P<0.05). Univariate and multivariate Cox regression model analysis suggested that high level of the preoperative NLR and d-NLR, together with the high level of NLR on postoperative day 3 were the independent influencing factors of poor DFS. High level of the preoperative NLR and d-NLR, together with the high level of NLR on postoperative day 3 were the independent influencing factors of OS. The level of PLR level was not correlated with DFS and OS. The C-index values of nomogram for predicting DFS and OS were 0.738 (95% confidence interval: 0.699-0.777) and 0.778 (95% confidence interval: 0.758-0.818), respectively. CONCLUSION: High level of the preoperative NLR, preoperative d-NLR and NLR on postoperative day 3 in ICC patients indicate poor prognosis, and PLR has no prognostic value for ICC patients after hepatectomy.

Identifying the Key Genes in Mouse Liver Regeneration After Partial Hepatectomy by Bioinformatics Analysis and in vitro/vivo Experiments.

BACKGROUND: The liver is the only organ that can completely regenerate after various injuries or tissue loss. There are still a large number of gene functions in liver regeneration that have not been explored. This study aimed to identify key genes in the early stage of liver regeneration in mice after partial hepatectomy (PH). MATERIALS AND METHODS: We first analyzed the expression profiles of genes in mouse liver at 48 and 72 h after PH from Gene Expression Omnibus (GEO) database. Gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analysis were performed to identify key genes in liver regeneration. Finally, we validated key genes in vivo and in vitro. RESULTS: We identified 46 upregulated genes and 19 downregulated genes at 48 h after PH, and 223 upregulated genes and 40 downregulated genes at 72 h after PH, respectively. These genes were mainly involved in cell cycle, DNA replication, and p53 signaling pathway. Among of these genes, cycle-related genes (Ccna2, Cdkn1a, Chek1, and Mcm5) and Ube2c were highly expressed in the residual liver both at 48 and 72 h after PH. Furthermore, Ube2c knockdown not only caused abnormal expression of Ccna2, Cdkn1a, Chek1, and Mcm5, but also inhibited transition of hepatocytes from G1 to S phase of the cell cycle in vitro. CONCLUSION: Mouse hepatocytes enter the proliferation phase at 48 h after PH. Ube2c may mediate cell proliferation by regulating or partially regulating Ccna2, Cdkn1a, Chek1, and Mcm5.