Lung cancer is the leading cause of cancer mortality in the United States. Non-small cell lung cancer accounts for 85% of all lung cancers for which adenocarcinoma is the most common histological type. Management of lung cancer is hindered by high false-positive rates due to difficulty resolving between benign and malignant tumors. Better molecular analysis comparing malignant and non-malignant tissues will provide important evidence of the underlying biology contributing to tumorigenesis. We utilized a proteomics approach to analyze 38 malignant and non-malignant paired tissue samples obtained from current or former smokers with early stage (Stage IA/IB) lung adenocarcinoma. Statistical mixed effects modeling and orthogonal partial least squares discriminant analysis were used to identify key cancer-associated perturbations in the adenocarcinoma proteome. Identified proteins were subsequently assessed against clinicopathological variables. Top cancer-associated protein alterations were characterized by: (1) elevations in APEX1, HYOU1 and PDIA4, indicative of increased DNA repair machinery and heightened anti-oxidant defense mechanisms; (2) increased LRPPRC, STOML2, COPG1 and EPRS, suggesting altered tumor metabolism and inflammation; (3) reductions in SPTB, SPTA1 and ANK1 implying dysregulation of membrane integrity; and (4) decreased SLCA41 suggesting altered pH regulation. Increased protein levels of HYOU1, EPRS and LASP1 in NSCLC adenocarcinoma was independently validated by tissue microarray immunohistochemistry. Immunohistochemistry for HYOU1 and EPRS indicated AUCs of 0.952 and 0.841, respectively, for classifying tissue as malignant. Increased LASP1 correlated with poor overall survival (HR 3.66 per unit increase; CI 1.37–9.78; p = 0.01). These results reveal distinct proteomic changes associated with early stage lung adenocarcinoma that may be useful prognostic indicators and therapeutic targets.

The long-term success of introduced populations depends on both their initial size and ability to compete against existing residents, but it remains unclear how these factors collectively shape colonization dynamics. Here, we investigate how initial population (propagule) size shapes the outcome of community coalescence by systematically mixing eight pairs of in vitro microbial communities at ratios that vary over six orders of magnitude, and we compare our results to neutral ecological theory. Although the composition of the resulting cocultures deviated substantially from neutral expectations, each coculture contained species whose relative abundance depended on propagule size even after ~40 generations of growth. Using a consumer–resource model, we show that this dose-dependent colonization can arise when resident and introduced species have high niche overlap and consume shared resources at similar rates. Strain isolates displayed longer-lasting dose dependence when introduced into diverse communities than in pairwise cocultures, consistent with our model’s prediction that propagule size should have larger, more persistent effects in diverse communities. Our model also successfully predicted that species with similar resource-utilization profiles, as inferred from growth in spent media and untargeted metabolomics, would show stronger dose dependence in pairwise coculture. This work demonstrates that transient, dose-dependent colonization dynamics can emerge from resource competition and exert long-term effects on the outcomes of community coalescence.

Background: Novel, non-invasive diagnostic biomarkers that facilitate early intervention in head and neck cancer are urgently needed. Polyamine metabolites have been observed to be elevated in numerous cancer types and correlated with poor prognosis. The aim of this study was to assess the concentration of polyamines in the saliva and urine from head and neck cancer (HNC) patients, compared to healthy controls. Methods: Targeted metabolomic analysis was performed on saliva and urine from 39 HNC patient samples and compared to 89 healthy controls using a quantitative, targeted liquid chromatography mass spectrometry approach. Results: The metabolites N¹-acetylspermine (ASP), N⁸-acetylspermidine (ASD) and N¹,N¹²-diacetylspermine (DAS) were detected at significantly different concentrations in the urine of HNC patients as compared to healthy controls. Only ASP was detected at elevated levels in HNC saliva as compared to healthy controls. Conclusion: These data suggest that assessment of polyamine-based metabolite biomarkers within the saliva and urine warrants further investigation as a potential diagnostic in HNC patients.