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Objectives: The tumor secretome deconvolution is a promising strategy to identify diagnostic and prognostic biomarkers. Here, transcriptomic-based secretome analysis was performed aiming to discover laryngeal squamous cell carcinomas (LSCC) biomarkers from potentially secreted proteins (PSPs)., Material and Methods: The tumor expression profile (35 LSCC biopsies compared with surrounding normal tissues - SN) revealed 589 overexpressed genes. This gene list was used for secretome analysis based on laryngeal tumors and related secretome databases., Results: Forty-nine (Laryngeal tumor secretome database) and 50 (Human Protein Atlas and Cancer Secretome Database) PSPs presented an association with worse overall survival. Specifically, DSG2 overexpression was strongly correlated with poor survival and distant metastasis. DSG2 increased expression was confirmed in the LSCC dataset (LSCC = 111; SN = 12) from TCGA. A significant association between shorter survival and DSG2 overexpression was also detected. In an independent cohort of cases, we analyzed and confirmed high protein levels of DSG2 in plasma from LSCC patients., Conclusion: A set of PSPs including the circulating DSG2, were associated with shorter overall survival in LSCC. DSG2 overexpression was also correlated with distant metastasis. The high plasmatic protein levels of DSG2 suggest its potential to be tested in liquid biopsies and applied as prognostic biomarker of LSCC., Competing Interests: Competing interests The authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The current treatment of laryngeal squamous cell carcinoma (LSCC) is based on radical surgery and radiotherapy resulting in high morbidity. Chemoradiotherapy has been used as alternative to organ sparing; however, several advanced cases presented resistance to treatment, which contributes to a high risk of recurrence and mortality. Coding RNAs and miRNAs have potential to be used as biomarkers or targets for cancer therapy., Materials and Methods: In this study, 36 LSCC and 5 non-neoplastic control samples were investigated using miRNA and mRNA large-scale expression analysis and a cross-validation was performed using the TCGA database (116 LSCC and 12 surrounding normal tissues)., Results: The large-scale profiling revealed the involvement of 28 miRNAs and 817 genes differentially expressed in LSCC. An integrative analysis comprising predicted and experimentally validated miRNA/mRNA interactions (negatively correlated), resulted in 28 miRNAs and 543 mRNAs. Decreased expression of miR-199b was significantly associated with shorter disease-free survival in LSCC (internal and TCGA datasets). The expression levels of selected miRNAs (miR-199b-5p, miR-29c-3p, miR-204-5p, miR-125b-5p and miR-92a-3p) and genes (COL3A1, COL10A1, ERBB4, HMGA2, HLF, TOP2A, MMP3, MMP13, MMP10 and PPP1R3) were confirmed as altered in LSCC by RT-qPCR. Additionally, a drug target prediction analysis revealed drug combinations based on miRNA and mRNA expression, pointing out novel alternatives to optimize the LSCC treatment., Conclusion: Collectively, these findings provide new insights in the LSCC transcriptional deregulation and potential drug targets., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)