Circulating Inflammation Proteins Associated With Lung Cancer in African Americans.

INTRODUCTION: Lung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) in the United States. We and others have previously shown a relationship between immune and inflammation proteins with lung cancer in EAs. Our aim was to investigate the etiologic relationship between inflammation and lung cancer in AAs. METHODS: We adopted a two-stage, independent study design (discovery cases, n = 316; control cases, n = 509) (validation cases, n = 399; control cases, n = 400 controls) and measured 30 inflammation proteins in blood using Meso Scale Discovery V- PLEX multiplex assays. RESULTS: We identified and validated 10 proteins associated with lung cancer in AAS, some that were common between EAs and AAs (C-reactive proteins [OR: 2.90; 95% confidence interval (CI): 1.99-4.22], interferon γ [OR: 1.55; 95% CI: 1.10-2.19], interleukin 6 [OR: 6.28; 95% CI: 4.10-9.63], interleukin 8 [OR: 2.76; 95% CI: 1.92-3.98]) and some that are only observed among AAs (interleukin 10 [OR: 1.69; 95% CI: 1.20-2.38], interleukin 15 [OR: 2.83; 95% CI: 1.96-4.07], interferon gamma-induced protein 10 [OR: 1.54; 95% CI: 1.09-2.18], monocyte chemotactic protein-4 [OR: 0.54; 95% CI: 0.38-0.76], macrophage inflammatory protein-1 alpha [OR: 1.57; 95% CI: 1.12-2.21], and tumor necrosis factor ß [OR: 0.52; 95% CI: 0.37-0.74]). We did not find evidence that either menthol cigarette smoking or global genetic ancestry drove these population differences. CONCLUSIONS: Our results highlight a distinct inflammation profile associated with lung cancer in AAs compared with EAs. These data provide new insight into the etiology of lung cancer in AAs. Further work is needed to understand what drives this relationship with lung cancer and whether these proteins have utility in the setting of early diagnosis.

Racial and Ethnic Differences in the Relationship between Aspirin Use and Non-Small Cell Lung Cancer Risk and Survival.

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.

Identification of serum inflammatory markers as classifiers of lung cancer mortality for stage I adenocarcinoma.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality worldwide. Low-dose CT (LDCT) imaging is now recommended to screen high-risk lung cancer individuals in the USA. LDCT has resulted in increased detection of stage I lung cancer for which the current standard of care is surgery alone. However, approximately 30% of these patients develop recurrence and therefore are in need of further treatment upon diagnosis. This study aims to explore blood-based inflammatory biomarkers to identify patients at high-risk of mortality for which additional treatment modalities can be offered at time of diagnosis. PATIENTS AND METHODS: Recent work on a small panel of circulating cytokines identified elevated levels of IL-6, a pro-inflammatory cytokine, as an indicator of poor survival for lung cancer patients. To reflect the broader role of inflammation in lung cancer, we examined a large panel of 33 inflammatory proteins in the sera of 129 lung cancer patients selected from the National Cancer Institute-Maryland case-control study. To reduce heterogeneity, we specifically focused our study on stage I lung adenocarcinoma patients. RESULTS: We replicated the previous observations that IL-6 is associated with prognosis of lung cancer and extended its utility to prognosis in this highly-selected population of stage I lung adenocarcinoma patients. In addition, we developed a multi-marker, combined prognostic classifier that includes the pro-inflammatory Th-17 cell effector cytokine, IL-17. Patients with high levels of IL-6 and IL-17A had a significantly adverse survival compared with patients with low levels (P for trend <0.0001). Patients in the high risk group, with high levels of both proteins had a 5-year survival rate of 46% in comparison to 93% for those with low levels of both markers. Furthermore, we validated the same trends for the IL-6 and IL-17A prognostic signature in an independent data set. CONCLUSIONS: The results identified here justify further investigation of this novel, combined cytokine prognostic classifier for the identification of high-risk stage I lung adenocarcinoma patients. This classifier has the much-needed potential to identify patients at high risk of recurrence and thus prospectively identify the subset of patients requiring more aggressive treatment regimens at the time of diagnosis.

ECM-based materials in cardiovascular applications: Inherent healing potential and augmentation of native regenerative processes.

The in vivo healing process of vascular grafts involves the interaction of many contributing factors. The ability of vascular grafts to provide an environment which allows successful accomplishment of this process is extremely difficult. Poor endothelisation, inflammation, infection, occlusion, thrombosis, hyperplasia and pseudoaneurysms are common issues with synthetic grafts in vivo. Advanced materials composed of decellularised extracellular matrices (ECM) have been shown to promote the healing process via modulation of the host immune response, resistance to bacterial infections, allowing re-innervation and reestablishing homeostasis in the healing region. The physiological balance within the newly developed vascular tissue is maintained via the recreation of correct biorheology and mechanotransduction factors including host immune response, infection control, homing and the attraction of progenitor cells and infiltration by host tissue. Here, we review the progress in this tissue engineering approach, the enhancement potential of ECM materials and future prospects to reach the clinical environment.