Mining the proteome: the application of tandem mass spectrometry to endocrine cancer research

Abstract

Tandem mass spectrometry (MS/MS) permits the detection of femtomolar quantities of protein from a wide variety of tissue sources. As endocrine cancers are frequently aetiologically complex, they are particularly amenable to mass spectrometry. The most widely studied aspect is the search for novel reliable biomarkers that would allow cancers to be diagnosed earlier and distinguished from benign tumours. MS/MS allows for the rapid analysis of blood and urine in addition to tumour tissue, and in this regard it has been applied on research involving thyroid, pancreatic, adrenal and ovarian cancers with varying degrees of success, as well as additional organ sites including breast and lung. The description of an individual cancer proteome potentially allows for personalised management of each patient, avoiding unnecessary therapies and targeting treatments to those which will have the most effect. The application of MS/MS to interaction proteomics is a field that has generated recent novel targets for chemotherapy. However, the technology involved in MS/MS has a number of drawbacks that at present prevent its widespread use in translational cancer research, including a poor reproducibility of results, in part due to the large amount of data generated and the inability to accurately differentiate true from false-positive results. Further, the current cost of running MS/MS restricts the number of times the experiments can be repeated, contributing to the lack of significance and concordance between studies. Despite these problems, however, MS/MS is emerging as a front line tool in endocrine cancer research and it is likely that this will continue over the next decade.

Differential Protein Expression Profiles of Cyst Fluid from Papillary Thyroid Carcinoma and Benign Thyroid Lesions

“…Proteomic techniques are increasingly applied in the search for diagnostic and prognostic markers in cancer [ 11 – 18 ]. In thyroid cancer, protein expression patterns have been evaluated by these techniques with the aim of distinguishing benign and malignant thyroid tumors [ 11 – 13 , 17 , 19 – 21 ]. Despite harboring various products of the epithelial cells’ activity, the liquid component of a thyroid cyst is routinely discarded in FNAB workflow.…”

Advances in the proteomic discovery of novel therapeutic targets in cancer

“…A large number of review articles have appeared in the past several years, offering excellent overviews and perspectives on novel proteomic applications in cancer. Many reviews focused on different cancer types, such as breast cancer,1–4 pancreatic cancer,5,6 ovarian cancer,7–9 colorectal cancer,10,11 and glioma 12–14. Others have focused on sample types or subcellular components, such as tissue,15–17 serum,18–20 and secretome 21–23.…”

Hands-on Workshops as An Effective Means of Learning Advanced Technologies Including Genomics, Proteomics and Bioinformatics

“…This includes relatively simple single nucleotide polymorphism (SNP) genotyping for determining an appropriate treatment plan to predicting the chemotherapeutic regimen most likely to benefit a breast cancer patient [3-5]. In addition, mass spectrometry, metabolomics, and proteomics are becoming essential for providing sensitive methods of characterizing and analyzing both small molecules and proteins [6-12]. Both genomics and proteomics have proven so successful in these regards that demand has far exceeded the supply of trained personnel equipped to exploit the available technologies.…”