Cover Picture: Proteomics – Clinical Applications 5/2009

AbstractIn this issue of Proteomics – Clinical Applications you will find the following highlighted articles:Proteomics gets savory: salivating againLast month in Proteomics 09/09 we looked at pea aphid saliva, this month we're considering human saliva. Vitorino et al. came out with all guns blazing as they hunted down the sources of the peptides found in human whole saliva (WS). Peptides in WS from six subjects were isolated and concentrated by three methods. They were then centrifuged to remove bacteria and debris with (i) nothing, (ii) 4 M guanidine‐HCl, or (iii) 0.1% trifluoroacetic acid added. Separation into HMW and LMW fractions was done by filtration through 100‐, 50‐, and 10 kDa cut‐off filters. Size limits were 700 to 16 000 Da. Samples were further analyzed by gelatinase zymogram electrophoresis, LC‐MALDI‐TOF/TOF, MALDI‐MS, LC‐MS/MS, and ex vivo proteolysis. Results: 2294 peptides identified (2210 LMW, of those 76% debris or plasma), 78 common to all samples. Cathepsin D appears to have been responsible for >40% of protease activity.Vitorino, R. et al., Proteomics Clin. Appl. 2009, 3, 528–540.Hepatocellular carcinoma markers: highest of the high, lowest of the lowHepatocellular carcinoma (HCC) rears its ugly head more than half a million times a year. It stands fifth on the frequency list but third on the killer list. If recognized in time, it can be controlled surgically. Thus the call for better biomarkers. Liver markers face the problem of being mostly serum proteins and must compete with highly abundant serum albumin and immunoglobulins. Wang et al. took a different approach, looking at both the secretomes and transcriptomes of HCC and normal tissues in serum‐free culture. Combining a five‐fold over‐expressed HCC marker with a five‐fold under‐expressed organ marker gave results better than either marker alone. The ratio of the pair, CHI3L1 and MASP2, had an area under curve score of 0.97, separately the AUC scores were 0.92 and 0.83 respectively.Wang, J. et al., Proteomics Clin. Appl. 2009, 3, 541–551.Multiple melanoma markers from plasmaMelanoma is one of the least frequent but most fatal skin cancers with a mortality rate of >80% and growing worldwide. Patients and research would benefit from improved prognostic and diagnostic markers, so Takikawa et al. took up the challenge. After depleting late‐stage melanotic and normal plasmas of the six most abundant protein species, samples were subjected to two dimensions of chromatography and, finally, MALDI‐TOF. After analysis and subtracting overlaps, 24 myeloma specific proteins remained, after applying stricter selection criteria, the count was down to nine. Four of the nine proteins also showed elevated transcript levels. Expression was also validated by Western blots and immunohistochemistry. One marker, PPBP, also shows a potential for being a prognostic indicator as well as a therapeutic target.Takikawa, M. et al., Proteomics Clin. Appl. 2009, 3, 552–562.