Machine Learning Model Based on the Neutrophil-to-Eosinophil Ratio Predicts the Recurrence of Hepatocellular Carcinoma After Surgery.

Background: Circulating eosinophils are associated with tumor development. An eosinophil-related index, the neutrophil to eosinophil ratio (NER), can be used to predict the prognosis of patients with tumors. However, there is still a lack of efficient prognostic biomarkers for HCC. In this study, we aimed to investigate the predictive value of the NER and develop an optimal machine learning model for the recurrence of HCC patients. Patients and methods: A retrospective collection of 562 patients who underwent hepatectomy with a pathologic diagnosis of HCC was performed. The relationship between NER and progression-free survival (PFS) was investigated. We developed a new machine learning framework with 10 machine learning algorithms and their 101 combinations to select the best model for predicting recurrence after hepatectomy. The performance of the model was assessed by the area under the curve (AUC) of characteristics and calibration curves, and clinical utility was evaluated by decision curve analysis (DCA). Results: Kaplan‒Meier curves showed that the PFS in the low NER group was significantly better than that in the high NER group. Multivariate Cox regression analysis showed that NER was an independent risk factor for recurrence after surgery. The random survival forests (RSF) model was selected as the best model that had good predictive efficacy and outperformed the TNM, BCLC, and CNLC staging systems. Conclusion: The NER has good predictive value for postoperative recurrence in patients with hepatocellular carcinoma. Machine learning model based on NER can be used for accurate predictions.

Pancreatobiliary reflux increases macrophage-secreted IL-8 and activates the PI3K/NFκB pathway to promote cholangiocarcinoma progression.

BACKGROUND: Persistent pancreaticobiliary reflux (PBR) is associated with a high risk of biliary malignancy. This study aimed to evaluate the proportion of PBR in biliary tract diseases and mechanisms by which PBR promoted cholangiocarcinoma progression. METHODS: Overall 227 consecutive patients with primary biliary tract disease participated in this study. The amylase levels in the collected bile were analyzed. The mechanisms underlying the effect of high-amylase bile on bile duct epithelial and cholangiocarcinoma cells progression were analyzed. The source of interleukin-8 (IL-8) and its effects on the biological functions of cholangiocarcinoma cells were investigated. RESULTS: The bile amylase levels in 148 of 227 patients were higher than the upper serum amylase limit of 135 IU/L. PBR was significantly correlated with sex, pyrexia, and serum gamma-glutamyl transferase (GGT) levels in the patient cohort. High-amylase bile-induced DNA damage and genetic differences in the transcript levels of the gallbladder mucosa and facilitated the proliferation and migration of bile duct cancer cells (HUCCT1 and QBC939 cells). The concentration of many cytokines increased in high-amylase bile. IL-8 is secreted primarily by macrophages via the mitogen-activated protein kinase pathway and partially by bile duct epithelial cells. IL-8 promotes the progression of HUCCT1 and QBC939 cells by regulating the expression of epithelial-mesenchymal transition-associated proteins and activating the phosphatidylinositol 3-kinase/nuclear factor kappa-B pathway. CONCLUSIONS: PBR is one of the primary causes of biliary disease. IL-8 secreted by macrophages or bile duct epithelial cells stimulated by high-amylase bile promotes cholangiocarcinoma progression.

Circulating the HLA-DR+ T Cell Ratio Is a Prognostic Factor for Recurrence of Patients with Hepatocellular Carcinoma after Curative Surgery.

Background: HLA-DR+ T cell, accounting for 1.2%-5.8% of peripheral lymphocyte, is a type of activated T lymphocyte. This retrospective study aimed to evaluate the prognostic value of HLA-DR+ T cell for progression-free survival (PFS) and overall survival (OS) in hepatocellular carcinoma (HCC) patients after curative surgery. Patients and Methods. Clinicopathological data of 192 patients who underwent curative resection for hepatocellular carcinoma in the affiliated hospital of Qingdao University between January 2013 and December 2021 were collected and analyzed. Statistical tests used in this study were the chi-square test and Fisher's exact test. The prognostic value of the HLA-DR+ T cell ratio was analyzed using univariate and multivariate Cox regression analyses. The Kaplan-Meier curves were drawn by the R programming language. Results: HCC patients were divided into high (≥5.8%) and low (<5.8%) HLADR+ T cell ratio groups. Cox regression analysis indicated that a high HLA-DR+ T cell ratio was positively related to the PFS in HCC patients (P=0.003) and AFP-positive (≥20 ng/ml) HCC patients (P=0.020). HCC patients and AFP-positive HCC patients in the high HLA-DR+ T cell ratio group were prone to have a higher T cell ratio, a higher CD8+T cell ratio, and a lower B cell ratio than the low HLA-DR+ T cell ratio group. However, the HLA-DR+ T cell ratio was not a statistically significant predictor for OS in HCC patients (P=0.57) as well as PFS (P=0.088) and OS (P=0.63) in AFP-negative HCC patients. Conclusions: This study confirmed that the HLA-DR+ T cell ratio was a significant predictor of PFS in HCC patients and AFP-positive HCC patients after curative surgery. This association may have guiding significance for the follow-up work of HCC patients after surgery.