Mass spectrometry (MS), a core technology for proteomics and metabolomics, is currently being developed for clinical applications. The identification of microorganisms in clinical samples using matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS) is a representative MS-based proteomics application that is relevant to daily clinical practice. This technology has the advantages of convenience, speed, and accuracy when compared with conventional biochemical methods. MALDI-TOF MS can shorten the time used for microbial identification by about 1 day in routine workflows. Sample preparation from microbial colonies has been improved, increasing the accuracy and speed of identification. MALDI-TOF MS is also used for testing blood, cerebrospinal fluid, and urine, because it can directly identify the microorganisms in these liquid samples without prior culture or subculture. Thus, MALDI-TOF MS has the potential to improve patient prognosis and decrease the length of hospitalization and is therefore currently considered an essential tool in clinical microbiology. Furthermore, MALDI-TOF MS is currently being combined with other technologies, such as flow cytometry, to expand the scope of clinical applications.

The expression of immune checkpoint proteins such as programmed cell death protein 1 (PD‐1) and its ligand (PD‐L1) has been shown to correlate with patient prognosis in many malignant cancers. The expression of PD‐L1 is controlled by c‐Myc; however, further upstream regulation of PD‐L1 expression is largely unknown. We have previously shown that atypical protein kinase C lambda/iota (aPKCλ) phosphorylates the Forkhead box protein O1 (FoxO1) transcription factor at Ser218 to suppress its DNA‐binding ability, thereby regulating c‐Myc expression and controlling physiologic and pathologic endothelial proliferation. The presence of phosphorylation of FoxO1 at Ser218 (pSer218 FoxO1) in cutaneous angiosarcoma (CAS) strongly correlates with poor patient prognosis. Here, we reported that patients with PD‐L1⁺ cells in CAS lesions showed significantly worse prognosis compared to those that were PD‐L1⁻. Expression of PD‐L1 correlated with that of aPKCλ or the presence of pSer218FoxO1. Moreover, suppression of aPKCλ expression or inhibition of its activity in HUVECs or AS‐M, an established human angiosarcoma cell line, resulted in decreased PD‐L1 expression. Our results suggest that combined treatment with immune checkpoint inhibitors and aPKCλ inhibitors could be a novel treatment strategy for CAS patients.

With the recent development of novel molecular targeted drugs for advanced stage malignant melanoma (MM), including RAF and mitogen‐activated protein kinase kinase inhibitors and immune checkpoint blockers, the early detection of relapse is important for managing patients with MM. In this study, we retrospectively analyzed two conventional serum biomarkers, 5‐S‐cysteinyl‐dopa and lactate dehydrogenase, in patients with MM (n = 140) who were treated at a single Japanese institute from June 2007 to June 2015. At the initial hospital visit, serum 5‐S‐cysteinyl‐dopa levels were significantly increased in patients with stages III (n = 38) and IV (n = 20) MM compared with patients with stages 0–II (n = 62) MM. In addition, in patients with stages III and IV MM, serum 5‐S‐cysteinyl‐dopa levels of more than 15.0 nmol/L at initial hospital visit correlated with a poor prognosis. In 11 of 14 patients whose disease progressed during follow up (mostly from stages III–IV), serum 5‐S‐cysteinyl‐dopa levels exceeded the normal limit of 10.0 nmol/L during the clinical detection of distant metastases. These results indicate the usefulness of measuring serum 5‐S‐cysteinyl‐dopa levels at initial hospital visit and during follow up for early and effective therapeutic interventions using newly developed molecular targeted drugs.

Cutaneous angiosarcoma (CAS) is a rare soft tissue sarcoma with rapid growth and poor prognosis. We retrospectively analyzed the data of 18 patients with CAS who underwent ¹⁸F‐Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) at the initial visit to the Department of Dermatology, Okayama University Hospital from September 2006 to March 2016. In the univariate survival analysis, patients with high standardized uptake values (SUV_max) of the primary tumor showed significantly poorer prognosis than those with low SUV_max. Early assessment of prognosis using PET/CT may predict patient survival and is useful in the selection of therapeutic strategies.

Recent advances in sophisticated technologies in proteomics should provide promising ways to discover novel markers for hepatocellular carcinoma (HCC) in the early diagnosis. Serum peptide and protein profiling was conducted by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Profiling was carried out in a training set of 16 patients with HCC and a testing set of 15 patients with cirrhosis without HCC. All the patients were hepatitis C virus positive. Candidate peaks were processed to partial purification, followed by protein identification by amino acid sequence analysis. Immunoprecipitation was conducted to confirm the protein identity. Partial purification and protein identification revealed that one peak that was up-regulated in HCC sera both in the training and the testing sets was a fragment of apolipoprotein A-I (apo A-I). Immunoprecipitation confirmed this result. MALDI-TOF MS analysis revealed that apo A-I is a potential novel serum marker of HCC. Combination of these pretreatments and the current magnet bead–assisted MALDI-TOF MS will further enhance the efficiency of biomarker discovery for HCC.