High KRT8 Expression Independently Predicts Poor Prognosis for Lung Adenocarcinoma Patients.

Keratin 8 (KRT8), a type II basic intermediate filament (IF) protein, is essential for the development and metastasis of various cancers. In this study, by analyzing RNA-seq data from the Cancer Genome Atlas (TCGA)-lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), we have determined the expression profile of KRT8, and assessed its prognostic significance and the possible mechanism underlying the dysregulation. Our results showed that KRT8 mRNA expression was significantly up-regulated in both LUAD and LUSC tissues compared with normal lung tissues. The high KRT8 expression group for LUAD patients significantly reduced overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate analysis revealed that KRT8 expression was an independent prognostic indicator for poor OS and RFS in LUAD patients. However, KRT8 expression had no prognostic value in terms of OS and RFS for LUSC. By exploring DNA copy number alterations (CNAs) of the KRT8 gene in LUAD, we found that DNA low copy gain (+1 and +2) was associated with elevated KRT8 mRNA expression. From the above findings, we have deduced that KRT8 is aberrantly expressed in LUAD tissues and that its expression might independently predict poor OS and RFS for LUAD patients, but not for LUSC patients.

The Capacity of Mycobacterium tuberculosis To Survive Iron Starvation Might Enable It To Persist in Iron-Deprived Microenvironments of Human Granulomas.

This study was conducted to investigate the role of iron deprivation in the persistence of Mycobacterium tuberculosis We present evidence of iron restriction in human necrotic granulomas and demonstrate that under iron starvation M. tuberculosis persists, refractive to antibiotics and capable of restarting replication when iron is made available. Transcriptomics and metabolomic analyses indicated that the persistence of M. tuberculosis under iron starvation is dependent on strict control of endogenous Fe utilization and is associated with upregulation of pathogenicity and intrinsic antibiotic resistance determinants. M. tuberculosis mutants compromised in their ability to survive Fe starvation were identified. The findings of this study advance the understanding of the physiological settings that may underpin the chronicity of human tuberculosis (TB) and are relevant to the design of effective antitubercular therapies.IMPORTANCE One-third of the world population may harbor persistent M. tuberculosis, causing an asymptomatic infection that is refractory to treatment and can reactivate to become potentially lethal tuberculosis disease. However, little is known about the factors that trigger and maintain M. tuberculosis persistence in infected individuals. Iron is an essential nutrient for M. tuberculosis growth. In this study, we show, first, that in human granulomas the immune defense creates microenvironments in which M. tuberculosis likely experiences drastic Fe deprivation and, second, that Fe-starved M. tuberculosis is capable of long-term persistence without growth. Together, these observations suggest that Fe deprivation in the lung might trigger a state of persistence in M. tuberculosis and promote chronic TB. We also identified vulnerabilities of iron-restricted persistent M. tuberculosis, which can be exploited for the design of new antitubercular therapies.