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.

BackgroundTargeting fibroblast growth factor receptor 1 (FGFR1) is a potential treatment for squamous cell lung cancer (SQCLC). So far, treatment decision in clinical studies is based on gene amplification. However, only a minority of patients have shown durable response. Furthermore, former studies have revealed contrasting results regarding the impact of FGFR1 amplification and expression on patient's prognosis.AimsHere, we analyzed prevalence and correlation of FGFR1 gene amplification and protein expression in human lung cancer and their impact on overall survival.Materials & MethodsFGFR1 gene amplification and protein expression were analyzed by fluorescence in situ hybridization and immunohistochemistry (IHC) in 208 SQCLC and 45 small cell lung cancers (SCLC). Furthermore, FGFR1 protein expression was analyzed in 121 pulmonary adenocarcinomas (ACs). Amplification and expression were correlated to each other, clinicopathological characteristics, and overall survival.ResultsFGFR1 was amplified in 23% of SQCLC and 8% of SCLC. Amplification was correlated to males (P = .027) but not to overall survival. Specificity of immunostaining was verified by cellular CRISPR/Cas9 FGFR1 knockout. FGFR1 was strongly expressed in 9% of SQCLC, 35% of AC, and 4% of SCLC. Expression was correlated to females (P = .0187) and to the absence of lymph node metastasis in SQCLC (P = .018) with no significant correlation to overall survival. Interestingly, no significant correlation between amplification and expression was detected.DiscussionFGFR1 gene amplification does not seem to correlate to protein expression.ConclusionWe believe that patient selection for FGFR1 inhibitors in clinical studies should be reconsidered. Neither FGFR1 amplification nor expression influences patient's prognosis.

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weeks, respectively. Results: Forty-four lung cancer patients were given IMMU-132 doses at 8 mg/kg (N = 23) or 10 mg/kg (N = 21); 38 patients (18 NSCLC and 20 SCLC) are assessable for efficacy. Patients were heavily pretreated (median of 3 prior lines). Objective tumor responses (all partial responses by RECIST1.1) and median progressionfree survival (PFS) are reported below per tumor. These studies are being expanded. Tumor typePrior lines of therapy: median (range)Objective Response Rate (PR)Median PFS (maturity) in months NSCLC (N=18) 3 (1-8) 33% 5.4 (56%) SCLC (N=20) 2.5 (1-7) 25% 2.4 (70%)IMMU-132 was well tolerated with limited grade 3/4 toxicities above the 3% threshold per patient. Neutropenia was the only Grade 3/4 toxicity (G3, 14%; G4, 7%) together with hyponatremia (G3, 2%; G4, 2%). Other drug-related G3 toxicities included diarrhea (7%), anemia (5%), leukopenia (5%), hyperglycemia (5%) and atrial fibrillation (5%); no patient developed antibodies to the conjugate. Conclusion: Repeated cycles of IMMU-132 monotherapy are well tolerated. Objective response rate and progressionfree survival data in previously-treated metastatic lung cancer (5.4 months in NSCLC) are encouraging and warrant further evaluation of IMMU-132 in these lung cancers.

Background: UDP-glucose-6-dehydrogenase (UGDH) plays an important role in the production of hyaluronic acid, an extracellular matrix component that is responsible for the promotion of normal cellular growth and migration. Increased levels of UGDH have been linked to the progression of epithelial cancers, such as those of the breast, colon and prostate. Therefore we aimed to analyze if the expression level of UGDH does also influence patients survival of lung cancer patients. Methods: UGDH expression levels were analyzed by immunohistochemistry in 96 samples of pulmonary adenocarcinoma (AC), 84 cases of squamous cell lung carcinoma (SQCLC) and 33 samples of small cell lung cancer (SCLC) and correlated with clinicopathologic characteristics and patient outcome. Results: UGDH was expressed in 62.5% cases of AC, 70.2% cases of SQCLC, and 48.5% cases of SCLC. In AC, expression of UGDH was significantly associated with lymph node metastasis and worse overall survival of the affected patients. However, UGDH expression had no significant correlation to prognosis in SQCLC or SCLC patients. Conclusions: In our study, expression of UGDH was associated with worse prognosis of patients with pulmonary adenocarcinoma so that expression of UGDH might help to guide treatment decisions. Furthermore, UGDH might present a potential novel drug target in AC as it displays inhibitable catalytic activity.