We propose to systematically identify a non-coding RNA (ncRNA) profile of exfoliated bronchial epitheliums of sputum from lung cancer patients. Bronchial epithelial cells enriched from sputum of 32 lung cancer patients and 33 cancer-free smokers were analyzed by next-generation sequencing to comprehensively characterize the ncRNA profiles. In addition, 108 miRNAs, 88 small nucleolar RNAs, 13 piwi-interacting RNAs, 6 transfer RNAs, 4 ribosomal RNAs, 19 small nuclear RNAs, and 25 long-noncoding (lnc) RNAs displayed a significantly different level in bronchial epitheliums of sputum of lung cancer patients versus cancer-free smokers (all <0.001). PCR analysis confirmed their different expression levels in the sputum specimens. A high expression of SNHG9, an lncRNA, was validated in 78 lung tumor tissues, and the expression was inversely associated with overall survival of lung cancer patients (p = 0.002). Knockdown of SNHG9 in cancer cells reduced the cell growth, proliferation, and invasion in vitro and tumorigenesis in vivo. The multiple differentially expressed ncRNAs in bronchial epitheliums may contribute to the development and progression of lung cancer and provide potential biomarkers and therapeutic targets for the disease.
Cytokines play crucial roles in tumorigenesis and are potential biomarkers for cancer diagnosis. An Enzyme-linked Immunosorbent Assay (ELISA) is commonly used to measure cytokines but has a low sensitivity and can only detect a single target at a time. CRISPR-Associated Proteins (Cas) can ultra-sensitively and specifically detect nucleic acids and is revolutionizing molecular diagnostics. Here, we design a microplate-based CRISPR-ELISA assay to simultaneously profile multiple cytokines, in which antibodies are coupled with ssDNA to form antibody-ssDNA complexes that bridges CRISPR/Cas12a and ELISA reactions. The ssDNA triggers the Cas12a collateral cleavage activity and releases the fluorescent reporters to generate amplified fluorescent signals in the ELISA detection of cytokines. The CRISPR-ELISA assay can simultaneously measure multiple cytokines with a significantly higher sensitivity compared with conventional ELISA. Using the CRISPR-ELISA assay to profile plasma cytokines in 127 lung cancer patients and 125 cancer-free smokers, we develop a panel of plasma cytokine biomarkers (IL-6, IL-8, and IL-10) for early detection of the disease, with 80.6% sensitivity and 82.0% specificity. The CRISPR-ELISA assay may provide a new approach to the discovery of cytokine biomarkers for early lung cancer detection.
Background: African Americans (AA) experience higher incidence and mortality of lung cancer as compared with European Americans (EA). Inflammation is associated with lung cancer, many aspects of which differ between AA and EA. We investigated whether use, frequency, and duration of the anti-inflammatory drug aspirin were associated with lung cancer risk and survival, separately among AA and EA populations. Methods: Using data from the Maryland Non–Small Cell Lung Cancer (NSCLC) Case–Control Study (1,220 cases [404 AA and 816 EA] and 1,634 controls [1,004 EA and 630 AA]), we estimated the adjusted odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) of the associations between aspirin use and NSCLC risk and survival, respectively. Results: Any aspirin use (OR: 0.66; 95% CI, 0.49–0.89), daily use of ≥ 1 tablet (OR: 0.68; 95% CI, 0.50–0.90), and use for ≥ 3 years (OR: 0.61; 95% CI, 0.44–0.85) was associated with lower NSCLC risk only among men, even after adjustment for covariates including body mass index and global genetic ancestry. These variables were also associated with improved survival, but only among AA (HR: 0.64; 95% CI, 0.46–0.91; HR: 0.61; 95% CI, 0.42–0.90; and HR: 0.60; 95% CI, 0.39–0.92, respectively). Tylenol and other NSAIDs were either associated with elevated or no NSCLC risk. Conclusions: Aspirin use is associated with lower risk of NSCLC among men and improved survival among AA. Impact: Preventive regular aspirin use could be considered among men and AA.
1 January 2021 in Respiratory Medicine Case Reports
Pulmonary talcosis is a rare pneumoconiosis that is difficult to diagnose and may progress to debilitating lung disease. Four types of talcosis are described in literature: talc-silicosis and talc-asbestosis secondary to inhalation in industry workers and talc-emboli in intravenous drug users that self-inject talc-containing oral tablets. Although found in common household products, talc is overlooked as a cause of pneumoconiosis. Talcosis caused by cosmetic face powder is even rarer. Here we discuss a woman in her 50s who developed talcosis from inhalation of cutaneous cosmetics two years prior, and how comprehensive history may be crucial in diagnosing this rare disease.
Amyloidosis is a unique disease of localised or systemic deposition of the abnormal extracellular fibril. Localised amyloidosis generally takes a benign course, while systemic requires treatment. Adenopathy, especially mediastinal adenopathy, is an unusual manifestation of localised amyloidosis and often requires mediastinoscopy or surgical resection for diagnosis. With the advent of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), there is potential for a less invasive diagnostic approach. We report a rare case of localised mediastinal amyloidosis diagnosed by EBUS-TBNA.