Abstract
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.
Highlights
Head-and-neck squamous cell carcinoma (HNSCC) affects more than 500,000 patients every year worldwide (Ferlay et al, 2010; Jemal et al, 2011; Chaturvedi et al, 2013)
Because the two tumour types have not been systematically compared at the proteome level, we wished to explore the possibility of identifying proteomic diagnostic biomarkers
Owing to the large number of morphological and genomic features that are shared by these tumour entities, diagnostic biomarkers are lacking so far and the clinical criteria currently used for differentiation between these tumour types are poorly validated and unreliable (Ichinose et al, 2016b)
Summary
Head-and-neck squamous cell carcinoma (HNSCC) affects more than 500,000 patients every year worldwide (Ferlay et al, 2010; Jemal et al, 2011; Chaturvedi et al, 2013). Differentiation between lung metastasis of HNSCC (metHNSCC) and SQCLC is of clinical importance, as the diagnosis guides the therapeutic procedures that can range from curative treatment for SQCLC patients to palliative treatment for patients with metastatic HNSCC (Atabek et al, 1987; Jacobs et al, 1992; Jones et al, 1995; Kuriakose et al, 2002; Henschke et al, 2003; Battafarano et al, 2004; Wisnivesky et al, 2004; Pignon et al, 2008; Shiono et al, 2009). Because decision-making by clinicians currently relies on non-validated clinical and imaging criteria, there is an urgent need for reliable molecular biomarkers that can differentiate between SQCLC and HNSCC lung metastases (Geurts et al, 2005)
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