Refine
Document Type
- Article (4)
Language
- English (4)
Has Fulltext
- yes (4)
Is part of the Bibliography
- no (4)
Keywords
- Biomarker (1)
- biogeography (1)
- climate (1)
- dispersal (1)
- head-and-neck cancer (1)
- invasion ecology (1)
- island (1)
- lung cancer (1)
- metastasis (1)
- niche (1)
Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis
(2018)
Patients with head‐and‐neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head‐and‐neck (HNSCC) carcinomas by quantitative proteomics. In a training cohort, we quantified 4,957 proteins in 44 SQCLC and 30 HNSCC tumours. A total of 518 proteins were found to be differentially expressed between SQCLC and HNSCC, and some of these were identified as genetic dependencies in either of the two tumour types. Using supervised machine learning, we inferred a proteomic signature for the classification of squamous cell carcinomas as either SQCLC or HNSCC, with diagnostic accuracies of 90.5% and 86.8% in cross‐ and independent validations, respectively. Furthermore, application of this signature to a cohort of pulmonary squamous cell carcinomas of unknown origin leads to a significant prognostic separation. This study not only provides a diagnostic proteomic signature for classification of secondary lung tumours in HNSCC patients, but also represents a proteomic resource for HNSCC and SQCLC.
Malignant germ cell tumors (GCT) are the most common malignant tumors in young men between 18 and 40 years. The correct identification of histological subtypes, in difficult cases supported by immunohistochemistry, is essential for therapeutic management. Furthermore, biomarkers may help to understand pathophysiological processes in these tumor types. Two GCT cell lines, TCam-2 with seminoma-like characteristics, and NTERA-2, an embryonal carcinoma-like cell line, were compared by a quantitative proteomic approach using high-resolution mass spectrometry (MS) in combination with stable isotope labelling by amino acid in cell culture (SILAC). We were able to identify 4856 proteins and quantify the expression of 3936. 347 were significantly differentially expressed between the two cell lines. For further validation, CD81, CBX-3, PHF6, and ENSA were analyzed by western blot analysis. The results confirmed the MS results. Immunohistochemical analysis on 59 formalin-fixed and paraffin-embedded (FFPE) normal and GCT tissue samples (normal testis, GCNIS, seminomas, and embryonal carcinomas) of these proteins demonstrated the ability to distinguish different GCT subtypes, especially seminomas and embryonal carcinomas. In addition, siRNA-mediated knockdown of these proteins resulted in an antiproliferative effect in TCam-2, NTERA-2, and an additional embryonal carcinoma-like cell line, NCCIT. In summary, this study represents a proteomic resource for the discrimination of malignant germ cell tumor subtypes and the observed antiproliferative effect after knockdown of selected proteins paves the way for the identification of new potential drug targets.
Aim: Biological invasions are likely determined by species dispersal strategies as well as environmental characteristics of a recipient region, especially climate and human impact. However, the contribution of climatic factors, human impact, and dispersal strategies in driving invasion processes is still controversial and not well embedded in the existing theoretical considerations. Here, we study how climate, species dispersal strategies, and human impact determine plant invasion processes on islands distributed in all major oceans in the context of directional ecological filtering.
Location: Six mountainous, tropical, and subtropical islands in three major oceans: Island of Hawai'i and Maui (Pacific), Tenerife and La Palma (Atlantic), and La Réunion and Socotra (Indian Ocean).
Taxon: Vascular Plants.
Methods: We recorded 360 non-native species in 218 plots along roadside elevational transects covering the major temperature, precipitation and human impact (i.e., road density) gradients of the islands. We collected dispersal strategies for a majority of the recorded species and calculated the environmental niche per species using a hypervolume approach.
Results: Non-native species’ generalism (i.e., mean community niche width) increased with precipitation, elevation and human impact but showed no relationship with temperature. Increasing precipitation led to environmental filtering of non-native species resulting in more generalist species under high precipitation conditions. We found no directional filtering for temperature but an optimum range of most species between 10 and 20°C. Niche widths of non-native species increased with the prevalence of certain dispersal strategies, particularly anemochory and anthropochory.
Main conclusions: Plant invasion on tropical and subtropical islands seems to be mainly driven by precipitation and human impact, while temperature seems to be of little importance. Furthermore, anemochory and anthropochory are dispersal strategies associated with large niche widths of non-native species. Our study allows a more detailed look at the mechanisms behind directional ecological filtering of non-native plant species in non-temperature-limited ecosystems.