No abstract

Rationale:The association between idiopathic pulmonary fibrosis (IPF) and lung cancer has been previously reported. However, there is the potential for significant confounding by age and smoking, and an accurate summary risk estimate has not been previously ascertained.Objectives: To determine the risk and burden of lung cancer in patients with IPF, accounting for known confounders.Methods: We conducted a comprehensive literature search of MEDLINE, EMBASE, and SCOPUS databases and used the Newcastle Ottawa criteria to assess study quality. We then assessed the quality of ascertainment of IPF cases based on modern consensus criteria. Data that relied on administrative claims or autopsies were excluded. We calculated summary risk estimates using a random effects model.Results: Twenty-five cohort studies were included in the final analysis. The estimated adjusted incidence rate ratio from two studies was 6.42 (95% confidence interval [CI], 3.21-9.62) and accounted for age, sex, and smoking. The summary incidence rate from 11 studies was 2.07 per 100 person-years (95% CI, 1.46-2.67), and the summary mortality rate was 1.06 per 100 person-years (95% CI, 0.62-1.51) obtained from three studies. The summary prevalence from 11 studies was 13.74% (95% CI, 10.17-17.30), and the proportion of deaths attributable to lung cancer was 10.20 (95% CI, 8.52-11.87) and was obtained from nine studies.Conclusions: IPF is an increased independent risk factor for lung cancer, even after accounting for smoking. Further well-designed studies using modern consensus criteria are needed to explore mechanisms of this association.

Background: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer with approximately half a million cases diagnosed each year worldwide. HNSCC has a poor survival rate which has not improved for over 30 years. The molecular pathogenesis of HNSCCs remains largely unresolved; there is high prevalence of p53 mutations and EGFR overexpression; however, the contribution of these molecular changes to disease development and/or progression remains unknown. We have recently identified microRNA miR-196a to be highly overexpressed in HNSCC with poor prognosis. Oncogenic miR-196a directly targets Annexin A1 (ANXA1). Although increased ANXA1 expression levels have been associated with breast cancer development, its role in HNSCC is debatable and its functional contribution to HNSCC development remains unclear. Methods: ANXA1 mRNA and protein expression levels were determined by RNA Seq analysis and immunohistochemistry, respectively. Gain-and loss-of-function studies were performed to analyse the effects of ANXA1 modulation on cell proliferation, mechanism of

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56dimCD57+ natural killer (NK) cells and exhausted CD8+ T cells. A similar transcriptome signature is replicated in an independent cohort of Kawasaki disease (KD), the related condition after which MIS-C was initially named. Probing a probabilistic causal network previously constructed from over 1,000 blood transcriptomes both validates the structure of this module and reveals nine key regulators, including TBX21, a central coordinator of exhausted CD8+ T cell differentiation. Together, this unbiased, transcriptome-wide survey implicates downregulation of NK cells and cytotoxic T cell exhaustion in the pathogenesis of MIS-C.