Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis

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.

Proteomic Analysis of Human Endometrial Tissues Reveals the Roles of PI3K/AKT/mTOR Pathway and Tumor Angiogenesis Molecules in the Pathogenesis of Endometrial Cancer

“…For example, Pan et al provided the detailed information of proteome alterations in bodily fluids of pancreatic cancer patients [ 18 ]. Bohnenberger et al studied the diagnostic proteomics of pulmonary head-and-neck cancer (HNSCC), providing the proteomic resource for HNSCC and squamous cell lung cancer (SQCLC) [ 19 ]. Chauvin and Boisvert described a method to compare protein expression and subcellular localization in different stages of colorectal cancer, which enables an integrated analysis of different kinds of cell lines and the function of pathways that cancer cell lines were involved in [ 20 ].…”

Multiclass cancer classification in fresh frozen and formalin-fixed paraffin-embedded tissue by DigiWest multiplex protein analysis

“…In a previous study, Bohnenberger et al [17] developed a classifier based on quantitative mass spectrometry data in FFPE samples, which differentiated between HNSC and LUSC with an accuracy of 86.8% in an independent test set [17]. However, more than 1100 proteins were necessary to achieve these results, and the accuracy decreased to 76.8% when only 100 proteins were included [17]. We demonstrated, based on the data of 102 antibodies, that it is possible to generate a classifier with comparable accuracy for discriminating five tumor types (77.6% accuracy in the paired set and 88% in the independent validation cohort) with DigiWest multiplex protein profiling.…”

“…Our classifier was able to distinguish with high accuracy between squamous cell carcinomas of different origins. In a previous study, Bohnenberger et al [17] developed a classifier based on quantitative mass spectrometry data in FFPE samples, which differentiated between HNSC and LUSC with an accuracy of 86.8% in an independent test set [17]. However, more than 1100 proteins were necessary to achieve these results, and the accuracy decreased to 76.8% when only 100 proteins were included [17].…”

“…Proteins are the principal effector molecules in a cell, and their function can be influenced by posttranslational modifications such as phosphorylation, acetylation, glycosylation, or sulphation [ 13 ]. Proteomic approaches have been successfully applied to differentiate cancer from nonmalignant tissue [ 14 – 16 ] or for the pairwise distinction of tumor types or subtypes [ 17 – 19 ]. However, so far, only a few studies have been conducted to classify multiple tumor types based on protein profiles in tissue samples [ 20 – 22 ].…”

Proteasome Inhibitor MG132 is Toxic and Inhibits the Proliferation of Rat Neural Stem Cells but Increases BDNF Expression to Protect Neurons

“…Different types of cells have cell-type-specific protein profile expression; moreover, gene transcription, translation, and protein degradation regulate the distinct proteome expression [2,[8][9][10]. Protein breakdown occurs in the lysosomes by acid hydrolases and in the proteasomes by an ATP-dependent mechanism [11].…”