The Prognostic Significance of Nomogram-Based Pretreatment Inflammatory Indicators in Patients With Esophageal Squamous Cell Carcinoma Receiving Intensity-Modulated Radiotherapy.

BACKGROUND: At present, there is no objective prognostic index available for patients with esophageal squamous cell carcinoma (ESCC) who underwent intensity-modulated radiotherapy (IMRT). This study is to develop a nomogram based on hematologic inflammatory indices for ESCC patients treated with IMRT. METHODS: 581 patients with ESCC receiving definitive IMRT were enrolled in our retrospective study. Of which, 434 patients with treatment-naïve ESCC in Fujian Cancer Hospital were defined as the training cohort. Additional 147 newly diagnosed ESCC patients were used as the validation cohort. Independent predictors of overall survival (OS) were employed to establish a nomogram model. The predictive ability was evaluated by time-dependent receiver operating characteristic curves, the concordance index (C-index), net reclassification index (NRI), and integrated discrimination improvement (IDI). Decision curve analysis (DCA) was performed to assess the clinical benefits of the nomogram model. The entire series was divided into 3 risk subgroups stratified by the total nomogram scores. RESULTS: Clinical TNM staging, primary gross tumor volume, chemotherapy, neutrophil-to-lymphocyte ratio and platelet lymphocyte ratio were independent predictors of OS. Nomogram was developed incorporating these factors. Compared with the 8th American Joint Committee on Cancer (AJCC) staging, the C-index for 5-year OS (.627 and .629) and the AUC value of 5-year OS (.706 and .719) in the training and validation cohorts (respectively) were superior. Furthermore, the nomogram model presented higher NRI and IDI. DCA also demonstrated that the nomogram model provided greater clinical benefit. Finally, patients with <84.8, 84.8-151.4, and >151.4 points were categorized into low-risk, intermediate-risk, and high-risk groups. Their 5-year OS rates were 44.0%, 23.6%, and 8.9%, respectively. The C-index was .625, which was higher than the 8th AJCC staging. CONCLUSIONS: We have developed a nomogram model that enables risk-stratification of patients with ESCC receiving definitive IMRT. Our findings may serve as a reference for personalized treatment.

Integrated analysis of methylation-driven genes and pretreatment prognostic factors in patients with hepatocellular carcinoma.

BACKGROUND: The potential reversibility of aberrant DNA methylation indicates an opportunity for oncotherapy. This study aimed to integrate methylation-driven genes and pretreatment prognostic factors and then construct a new individual prognostic model in hepatocellular carcinoma (HCC) patients. METHODS: The gene methylation, gene expression dataset and clinical information of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Methylation-driven genes were screened with a Pearson's correlation coefficient less than - 0.3 and a P value less than 0.05. Univariable and multivariable Cox regression analyses were performed to construct a risk score model and identify independent prognostic factors from the clinical parameters of HCC patients. The least absolute shrinkage and selection operator (LASSO) technique was used to construct a nomogram that might act to predict an individual's OS, and then C-index, ROC curve and calibration plot were used to test the practicability. The correlation between clinical parameters and core methylation-driven genes of HCC patients was explored with Student's t-test. RESULTS: In this study, 44 methylation-driven genes were discovered, and three prognostic signatures (LCAT, RPS6KA6, and C5orf58) were screened to construct a prognostic risk model of HCC patients. Five clinical factors, including T stage, risk score, cancer status, surgical method and new tumor events, were identified from 13 clinical parameters as pretreatment-independent prognostic factors. To avoid overfitting, LASSO analysis was used to construct a nomogram that could be used to calculate the OS in HCC patients. The C-index was superior to that from previous studies (0.75 vs 0.717, 0.676). Furthermore, LCAT was found to be correlated with T stage and new tumor events, and RPS6KA6 was found to be correlated with T stage. CONCLUSION: We identified novel therapeutic targets and constructed an individual prognostic model that can be used to guide personalized treatment in HCC patients.

Prognostic value of fatty acid metabolism-related genes in patients with hepatocellular carcinoma.

The deregulation of fatty acid metabolism plays a crucial role in cancer. However, the prognostic value of genes involved in the metabolism in hepatocellular carcinoma (HCC) remains largely unknown. We first constructed a multi-fatty acid metabolic gene prognostic model of HCC based on The Cancer Genome Atlas (TCGA) and further validated it using the International Cancer Genome Consortium (ICGC) database. The model was integrated with the clinical parameters, and a nomogram was built and weighted. Moreover, immune cell infiltration of the tumor microenvironment was investigated. A prognostic model was constructed using 6 selected fatty acid metabolism-related genes, and HCC patients were divided into high- and low-risk groups. Receiver operating characteristic curve (ROC) analysis, principal component analysis (PCA), and t-distributed stochastic neighbor embedding (t-SNE) analysis showed the optimal performance of the model. The concordance index (C-index), ROC curve, calibration plot and decision curve analysis (DCA) all confirmed the satisfactory predictive capacity of the nomogram. The analysis of immune cell infiltration in HCC patients revealed a correlation with different risk levels. Our findings indicate that a prognostic model based on fatty acid metabolism-related genes has superior predictive capacities, which provides the possibility for further improving the individualized treatment of patients with HCC.

Prognostic Value of a Ferroptosis-Related Gene Signature in Patients With Head and Neck Squamous Cell Carcinoma.

Background: Ferroptosis is an iron-dependent programmed cell death (PCD) form that plays a crucial role in tumorigenesis and might affect the antitumor effect of radiotherapy and immunotherapy. This study aimed to investigate distinct ferroptosis-related genes, their prognostic value and their relationship with immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC). Methods: The differentially expressed ferroptosis-related genes in HNSCC were filtered based on multiple public databases. To avoid overfitting and improve clinical practicability, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were performed to construct a prognostic risk model. Moreover, a nomogram was constructed to forecast individual prognosis. The differences in tumor mutational burden (TMB), immune infiltration and immune checkpoint genes in HNSCC patients with different prognoses were investigated. The correlation between drug sensitivity and the model was firstly analyzed by the Pearson method. Results: Ten genes related to ferroptosis were screened to construct the prognostic risk model. Kaplan-Meier (K-M) analysis showed that the prognosis of HNSCC patients in the high-risk group was significantly lower than that in the low-risk group (P < 0.001), and the area under the curve (AUC) of the 1-, 3- and 5-year receiver operating characteristic (ROC) curve increased year by year (0.665, 0.743, and 0.755). The internal and external validation further verified the accuracy of the model. Then, a nomogram was build based on the reliable model. The C-index of the nomogram was superior to a previous study (0.752 vs. 0.640), and the AUC (0.729 vs. 0.597 at 1 year, 0.828 vs. 0.706 at 3 years and 0.853 vs. 0.645 at 5 years), calibration plot and decision curve analysis (DCA) also shown the satisfactory predictive capacity. Furthermore, the TMB was revealed to be positively correlated with the risk score in HNSCC patients (R = 0.14; P < 0.01). The differences in immune infiltration and immune checkpoint genes were significant (P < 0.05). Pearson analysis showed that the relationship between the model and the sensitivity to antitumor drugs was significant (P < 0.05). Conclusion: Our findings identified potential novel therapeutic targets, providing further potential improvement in the individualized treatment of patients with HNSCC.

Polydopamine coating on individual cells for enhanced extracellular electron transfer.

A new strategy of redox mediator immobilization was developed by coating polydopamine (PDA) on individual live cells to enhance extracellular electron transfer. As a result of the synergistic effect of the redox properties of PDA and the ability to adsorb self-secreted flavin molecules, a double-mediator electron transport channel was achieved.