Construction and validation of a novel web-based nomogram for patients with lung cancer with bone metastasis: A real-world analysis based on the SEER database.

Purpose: Patients with lung cancer with bone metastasis (LCBM) often have a very poor prognosis. The purpose of this study is to characterize the prevalence and associated factors and to develop a prognostic nomogram to predict the overall survival (OS) and cancer-specific survival (CSS) for patients with LCBM using multicenter population-based data. Methods: Patients with LCBM at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) Program database of the National Cancer Institute (NCI) from 2010 to 2015. Multivariable and univariate logistic regression analyses were performed to identify factors associated with all-cause mortality and lung cancer (LC)-specific mortality. The performance of the nomograms was evaluated with the calibration curves, area under the curve (AUC), and decision curve analysis (DCA). Kaplan-Meier analysis and log-rank tests were used to estimate the survival times of patients with LCBM. Results: We finally identified 26,367 patients with LCBM who were selected for survival analysis. Multivariate analysis demonstrated age, sex, T stage, N stage, grade, histology, radiation therapy, chemotherapy, primary site, primary surgery, liver metastasis, and brain metastasis as independent predictors for LCBM. The AUC values of the nomogram for the OS prediction were 0.755, 0.746, and 0.775 in the training cohort; 0.757, 0.763, and 0.765 in the internal validation cohort; and 0.769, 0.781, and 0.867 in the external validation cohort. For CSS, the values were 0.753, 0.753, and 0.757 in the training cohort; 0.753, 0.753, and 0.757 in the internal validation cohort; and 0.767, 0.774, and 0.872 in the external validation cohort. Conclusions: Our study constructs a new prognostic model and clearly presents the clinicopathological features and survival analysis of patients with LCBM. The result indicated that the nomograms had favorable discrimination, good consistency, and clinical benefits in patients. In addition, our constructed nomogram prediction models may assist physicians in evaluating individualized prognosis and deciding on treatment for patients.

vFLIP-regulated competing endogenous RNA (ceRNA) networks targeting lytic induction for KSHV-associated malignancies.

Kaposi's sarcoma-associated herpesvirus (KSHV) causes life-long latent infection and malignancies, including KS commonly found in AIDS patients. Lytic replication can be induced to kill tumor cells harboring latent KSHV, through viral cytopathic effects and the subsequent antiviral immune responses. Viral FLICE-inhibitory protein (vFLIP), encoded by KSHV ORF K13, inhibits KSHV lytic reactivation, implying that the competing endogenous RNA (ceRNA) networks regulated by vFLIP can be modulated to induce the lytic reactivation of latent KSHV, a promising strategy for KSHV-associated malignancies. Here, we performed whole-transcriptome sequencing to reveal the global landscape of noncoding RNAs and messenger RNAs (mRNAs) in iSLK-RGB-BAC16 cells and iSLK-RGB-K13 mutant cells. It showed that vFLIP regulated 227 differentially expressed (DE) long non-coding RNAs (lncRNAs), 57 DE circular RNAs (circRNAs), 20 DE microRNAs (miRNAs), and 1371 DE mRNAs. Enrichment analysis verified that riboflavin metabolism was simultaneously enriched in DE genes related to miRNAs, lncRNAs, and circRNAs. The upregulated hsa-miR-378i and hsa-miR-3654, and downregulated miR-4467, miR-3163, miR-4451, and miR-4257 were significantly enriched in the ceRNA complex network, which contained 9 upregulated and 7 downregulated circRNAs, 5 upregulated and 85 downregulated lncRNAs, 5 upregulated and 35 downregulated mRNAs. Finally, we constructed and validated two vFLIP-regulated ceRNA networks: circRNA hsa_circ_0070049/hsa-miR-378i/SPEG/FOXQ1 and lncRNA AL031123.1/hsa-miR-378i/SPEG/FOXQ1. Taken together, the two ceRNA networks may mediate KSHV reactivation. These novel findings refreshed the present understanding of ceRNA network in KSHV lytic induction and provided potential therapeutic targets for KSHV-associated malignancies.

High Frequency of Microvascular Dysfunction in US Outpatient Clinics: A Sign of High Residual Risk? Data from 7,105 Patients.

Previous studies have linked peripheral microvascular dysfunction measured by arterial tonometry to high residual risk in on-statin patients. Digital thermal monitoring (DTM) of microvascular function is a new and simplified technique based on fingertip temperature measurements that has been correlated with the burden of atherosclerosis and its risk factors. Here, we report analyses of DTM data from two large US registries: Registry-I (6,084 cases) and Registry-II (1,021 cases) across 49 US outpatient clinics. DTM tests were performed using a VENDYS device during a 5-minute arm-cuff reactive hyperemia. Fingertip temperature falls during cuff inflation and rebounds after deflation. Adjusted maximum temperature rebound was reported as vascular reactivity index (VRI). VRI distributions were similar in both registries, with mean ± SD of 1.58 ± 0.53 in Registry-I and 1.52 ± 0.43 in Registry-II. In the combined dataset, only 18% had optimal VRI (≥2.0) and 82% were either poor (<1.0) or intermediate (1.0-2.0). Women had slightly higher VRI than men (1.62 ± 0.56 vs. 1.54 ± 0.47, p < 0.001). VRI was inversely but mildly correlated with age (r = -0.19, p < 0.001). Suboptimal VRI was found in 72% of patients <50 years, 82% of 50-70 years, and 86% of ≥70 years. Blood pressure was not correlated with VRI. In this largest registry of peripheral microvascular function measurements, suboptimal scores were highly frequent among on-treatment patients, possibly suggesting a significant residual risk. Prospective studies are warranted to validate microvascular dysfunction as an indicator of residual risk.